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Biomedical subjects

K McGee

Publications and source records attributed to K McGee.

At least 19 recordsLinked to original sources

Prevalence of severe welfare problems in horses that arrive at slaughter plants.

OBJECTIVE: To assess the prevalence of severe welfare problems in horses that arrive at slaughter plants and to identify horses that were unfit for travel. DESIGN: Prevalence survey. ANIMALS: 1,008 horses. PROCEDURE: Horses arriving at 2 slaughter plants were observed. The following were rated severe welfare problems in horses: body condition scores of 1 or 2 (emaciated) of 9; recumbency (down) or the inability to walk; fractured limbs or other foot or limb problems that extremely impaired mobility; severe wounds, such as deep cuts, extensive lacerations, abrasions on the head or back, eye injuries, neglected purulent lesions, and numerous bite and kick marks over extensive areas of the body; and dead on arrival. Bruises on carcasses were tabulated to further assess injuries. Horses that had been loaded with a fractured limb, arrived nonambulatory, had severe lameness that interfered with mobility, were weak and emaciated, or were dead on arrival or died shortly after arrival were considered unfit for travel. RESULTS: Ninety-two percent (930/1,008) of the horses arrived in good condition, and 7.7% (78) had a condition that was rated a serious welfare problem. Thirty horses (3%) had a body condition score of 1 or 2, 12 (1.0%) had foot and limb problems (other than fractures), 4 (0.4%) had fractured limbs, 18 (2.0%) had deep cuts, lacerations, or injuries from bites, 8 (0.8%) were nonambulatory or dead on arrival, 2 (0.2%) had deformities, 3 (0.3%) had extensive purulent lesions, and 1 (0.1%) had a behavior problem. Characteristic patterns of 51% of carcass bruises indicated that they were caused by bites or kicks. Fighting was the major cause of injuries that occurred during transport and marketing. Fifteen (1.5%) horses were unfit for travel. Abuse or neglect by owners was the cause of 77% of the severe welfare problems observed. CLINICAL IMPLICATIONS: To decrease the number of injuries that result from fighting when transporting horses to slaughter plants, aggressive mares and geldings that continually attack other horses must be segregated.

Abattoirs

YopH dephosphorylates Cas and Fyn-binding protein in macrophages.

The tyrosine phosphatase YopH is an essential virulence effector of pathogenic Yersinia spp. YopH, which is translocated from extracellularly located bacteria into interacting target cells, blocks phagocytosis by professional phagocytes. We show here that immunoprecipitation of YopH from lysates of J774 cells infected with Y. pseudotuberculosis expressing an inactive form of YopH resulted in co-precipitation of certain phosphotyrosine proteins. The association between the inactive YopH and phosphotyrosine proteins in the 120 kDa range was rapid and could be detected after 2 min of infection. The proteins were identified as the docking proteins Cas and Fyn-binding protein (FYB). Upon infection of J774 cells with Y. pseudotuberculosis lacking YopH expression both of these proteins became tyrosine phosphorylated. Moreover, this infection caused recruitment of Cas to peripheral focal complexes, and FYB was relocalized to areas surrounding these structures. Both Cas and FYB became dephosphorylated upon infection with Y. pseudotuberculosis expressing active YopH, and this was associated with disruption of focal complexes. With regard to the previous identification of Cas and focal complexes as targets of YopH in HeLa cells, the present study supports an important role for these targets in a general mechanism of bacterial uptake.

Bacterial Outer Membrane Proteins

Topiramate pharmacokinetics in infants.

PURPOSE: This study's goal was to provide preliminary data on the pharmacokinetics of topiramate (TPM) in a cohort of infants (younger than 4 years) participating in an open-label trial of TPM in refractory infantile spasms. METHODS: The pharmacokinetics of TPM were assessed in infants receiving a stable TPM dose for >7 days during the extension phase of this trial. Blood samples were drawn just before and 0.5. 1, 1.5, 2, 4, 6, 8, and 12 h after the morning TPM dose. TPM plasma concentrations were determined by fluorescence polarization immunoassay. The noncompartmental analysis module of WinNonlin was used to calculate individual patient pharmacokinetics profiles. RESULTS: Five infants (ages, 23.5-29.5 months) formed the study cohort. These infants had been given TPM for a median of 9 months (range, 6-11 months) and were currently receiving between 11 and 38.5 mg/kg/day TPM. One was receiving TPM monotherapy, whereas four were taking concomitant antiepileptic medications (AEDs; n = 2, enzyme-inducing agents; n = 2, non-enzyme-inducing drugs). TPM pharmacokinetics in infants appears to be linear. In this cohort, mean TPM plasma clearance (CL/F, 66.6+/-27.4 ml/h/kg) was slightly higher than that reported for children and adolescents and therefore substantially higher than that reported for adults. TPM CL/F was higher and the calculated half-life shorter in the infants receiving concomitant enzyme-inducing AEDs. CONCLUSIONS: Based on this small cohort of patients, it appears that infants may require significantly larger TPM doses, based on weight, than children, adolescents, or adults. Titration to effect and not absolute TPM dose should guide therapy in this age group.

Adolescent

Prospective double-arm study of fibrinolysis in surgical patients.

BACKGROUND: During surgery, the balance between thrombosis and fibrinolysis is altered. Methods reported to increase fibrinolysis, such as compression devices, may reduce venous thrombosis. However, there are no prospective studies comparing methods and the effect on fibrinolysis. MATERIALS AND METHODS: In a prospective study, general surgical patients were randomized to either sequential compression devices (Group 1) or subcutaneous heparin (Group 2), and fibrinolysis factors were measured in order to determine the effect on the fibrinolysis system. Blood samples were drawn at a similar time of the day with the tourniquet off. Specifically, t-PA antigen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer were measured preoperatively (preop) and on Postoperative Days (POD) 1 and 7 by the ELISA method. Fibrinolysis factors were reported as the mean +/- SD and as percentage change from preoperative values. Noninvasive vascular studies were performed preop, and on POD 1, 7, and 30, by an examination of the infrainguinal venous system and external iliac veins in bilateral lower extremities. Nonambulatory patients were excluded from the study and DVT prophylaxis methods were initiated at surgery and used through POD 2. RESULTS: For the 136 patients in the study, there were no differences in clinical characteristics such as age, surgical time (all > 60 min), anesthesia type (general or spinal), type of surgical procedure, or other risk factors for DVT. Two DVTs occurred at POD 1 and 30 (both Group 2), and one pulmonary embolism in each group (POD 7 for Group 1; POD 1 for Group 2). For subjects without thrombosis, D-dimer changes were parallel for both groups, increasing through POD 7. Similarly, t-PA antigen levels rose from baseline on POD 1 in both groups, with a return toward baseline by POD 7. The PAI-1 levels increased on POD 1 in both groups, but severalfold more in Group 1 (compression devices). The elevation in PAI-1 decreased by 50% in Group 1 by POD 7, while values returned to normal in Group 2. These changes were not significant using the Mann-Whitney test. Only three patients had thrombotic episodes so that data on changes in fibrinolysis factors are difficult to compare with the larger group. CONCLUSIONS: This is the first report of a prospective, randomized comparison of fibrinolysis factors using sequential compression devices in comparison to low dose unfractionated heparin in general surgical patients, and comparing postoperative values to preop. Both groups showed an enhanced fibrinolysis by elevation in t-PA antigen and D-dimer on POD 1, as expected when fibrinolysis occurs. While PAI-1 and t-PA work in parallel, the marked elevation of PAI-1 on POD 1 (although only slightly above reference values) and continuing into POD 7 for subjects using compression devices requires further inquiry. The elevation of PAI-1 in the face of elevated t-PA and D-dimer has been reported, but the comparison between patients using sequential compression devices and mini-dose heparin has not been reported. The reason for the elevation requires additional study into other influences on the synthesis, secretion, and/or function of PAI-1 that do not affect t-PA.

Female

Is DVT prophylaxis overemphasized? A randomized prospective study.

This study was designed to prospectively evaluate a previously published prognostic index for predicting deep venous thrombosis (DVT) in general surgical patients with conventional prophylaxis. Patients undergoing procedures of at least 1 hr duration (abdominal, thoracic, head and neck, inguinal) requiring general or spinal anesthetic were prospectively randomized into the following groups: Group 1, sequential pneumatic compression devices during surgery and 2 days postoperatively; Group 2, subcutaneous heparin (5000 U q 12 hr) starting 1 hr before surgery and for 7 days postop; Group 3, control group. All patients underwent duplex evaluation of bilateral lower extremity deep venous systems preoperatively and on postoperative Days 1, 3, and 30. In addition, a previously developed predictive DVT incidence indicator, the prognostic index (PI), was calculated for each patient. A total of 137 patients were entered into the study with 29 removed for patient/staff reasons. There were no differences in PI among the three groups at the 0.05 level (ANOVA). The distribution of risk factors for DVT including increased age, body size, hemoglobin (Hb), and colorectal procedures were distributed evenly among the groups. Additional factors such as diabetes, COPD, PVD, immobilization, and cancer were also evenly distributed among the groups. The PI predicted a 20% incidence of DVT. For Groups 1 (n = 25), 2 (n = 38), and 3 (n = 45) no DVTs were detected over the 30 days of study. During the study period, 8 DVTs were detected by duplex evaluation in general surgical patients not in the study (1.5%). In conclusion, in a prospective randomized study using sequential pneumatic compression devices, subcutaneous heparin or no prophylaxis in matched general surgical patients at moderate to high risk for thromboembolism, no DVTs occurred for up to 30 days. Furthermore, neither a PI nor other factors associated with DVT accurately predicted the incidence of DVT in this patient population.

Adult

5-Fluorouracil and cisplatin therapy after palliative surgical resection of squamous cell carcinoma of the esophagus. A multicenter randomized trial. French Associations for Surgical Research.

BACKGROUND: The curative rate of surgical resection of squamous cell carcinoma of the esophagus is low. Reports on the efficacy of preoperative and postoperative chemotherapy are conflicting or have included limited disease or radical surgery alone. OBJECTIVE: The authors' objective was to study the results of chemotherapy on the duration and quality of survival in patients who have undergone palliative surgical resection for esophageal squamous cell carcinoma. PATIENTS AND METHODS: Of 124 patients with histologically proven esophageal squamous cell carcinoma situated more than 5 cm from the upper end of the esophagus, 4 patients were withdrawn for failure to comply with the protocol. The remaining 120 patients, 116 males and 4 females (mean age, 57 +/- 9 years), were randomly assigned to either a control group who were to receive no chemotherapy (68 patients) or to a group who were to be treated with chemotherapy (52 patients). Patients were subdivided into two strata as follows: (1) stratum I, complete resection of the tumor with lymph node involvement (62 patients) and (2) stratum ii, incomplete resection leaving macroscopic tumor tissue in situ or with metastases. Noninclusion criteria were histologically proven tracheobronchial involvement, esotracheal fistula, major alteration of general health status (Karnofsky score <50), cerebral or extensive (>30% of parenchyma) hepatic metastasis, peritoneal carcinomatosis, associated or previously treated upper airway cancer, or, conversely, complete resection of tumor without lymph node involvement. Chemotherapy was given in 5-day courses, every 28 days, with a maximum of 8 courses. Cisplatin was administered either as a single dose of 100 mg/m2 at the beginning of the course or as 20 mg/m2/day for 5 days given over 3 hours. 5- Fluorouracil (5-FU) (100 mg/m2/day) was infused over 24 hours for 5 days. The duration of treatment ranged from 6 to 8 months. The main aim was to establish median survival and actuarial survival curves. The subsidiary aim was to evaluate quality of survival as judged by complications due to treatment and the duration of autonomous oral feeding, that is, without palliative endoscopic treatment. No difference in survival was noted between the two groups, overall (median, 14 months), or between the strata. Conversely, significantly more patients in the treated group had hematologic, neurologic, and renal complications compared with the control group. Four patients died of complications of chemotherapy. The duration of autonomous oral alimentation was exactly the same in both groups (median, 12 + months). CONCLUSION: The results of this study suggest that 5-FU and cisplatin are not useful for patients with squamous cell carcinoma of the esophagus who have not undergone curative resection.

Actuarial Analysis

Identification and characterization of additional flagellin genes from Vibrio anguillarum.

Previously, the flagellar filament of Vibrio anguillarum was suggested to consist of flagellin A and three additional flagellin proteins, FlaB, -C, and -D. This study identifies the genes encoding FlaB, -C, and -D and a possible fifth flagellin gene that may encode FlaE. The flagellin genes map at two separate DNA loci and are most similar to the four polar flagellin genes of Vibrio parahaemolyticus, also located at two DNA loci. The genetic organization of these two loci is conserved between both organisms. For each gene, in-frame deletions of the entire gene, the 5' end, and the 3' end were made. Mutant analysis showed that each mutation, except those in flaE, caused a loss of flagellin from the filament. However, no obvious structural loss in the filament, as determined by electron microscopy, and only slight decreases in motility were seen. Virulence analysis indicated that all but two of the mutations gave a wild-type phenotype. The 5'-end deletions of flaD and flaE decreased virulence significantly (>10(4)-fold) of infections via both the intraperitoneal and immersion routes. These results indicate that, like FlaA, FlaD and FlaE may also be involved in virulence.

Amino Acid Sequence

[Monitoring of multiple trauma in an emergency hospital unit].

In the monitoring of multiple trauma patients in the emergency hospital setting the use of monitors should be graduated. However, the use and interpretation of data from these monitors is becoming increasingly complex and can lead to errors and responses which may not be adopted. Clinical nomination and observation have their limits and the anaesthetist is faced with the added difficulties of interpretation of data from monitors and is pitfalls. The management of the patient is based on this human-machine relationship, which provides the basis for the therapeutic attitude and the treatment which ensues. Basic monitoring comprises a pulse oximeter, a capnograph, an ECG and a blood pressure monitor, 52% of incidents are detected by these instruments; 27% by SpO2, 24% by capnography. The pertinence is 82% for the oximeter when used alone and 55% for the capnography alone, although when the two are used together this increases to 88%. If the blood pressure monitor is added the pertinence increases to 93%, and to 95% if the FiO2 is monitored. The use of monitors of levels of haemoglobin or haematocrit must take into account the important variations in volaemia. The displayed values have a poor predictive value. The second level of monitoring comprises the use of a pulmonary artery catheter. The errors in measurement and interpretation are reviewed and finally, we consider the possible use of FOE transoesophageal echocardiography in the multiple trauma patient.

Blood Pressure Determination

The uncertain response in the bottlenosed dolphin (Tursiops truncatus).

Humans respond adaptively to uncertainty by escaping or seeking additional information. To foster a comparative study of uncertainty processes, we asked whether humans and a bottlenosed dolphin (Tursiops truncatus) would use similarly a psychophysical uncertain response. Human observers and the dolphin were given 2 primary discrimination responses and a way to escape chosen trials into easier ones. Humans escaped sparingly from the most difficult trials near threshold that left them demonstrably uncertain of the stimulus. The dolphin performed nearly identically. The behavior of both species is considered from the perspectives of signal detection theory and optimality theory, and its appropriate interpretation is discussed. Human and dolphin uncertain responses seem to be interesting cognitive analogs and may depend on cognitive or controlled decisional mechanisms. The capacity to monitor ongoing cognition, and use uncertainty appropriately, would be a valuable adaptation for animal minds. This recommends uncertainty processes as an important but neglected area for future comparative research.

Animals

Sevoflurane elimination kinetics in children.

We compared the rates of elimination of sevoflurane and halothane in 29 children, aged between one and seven years, undergoing ambulatory anaesthesia. Analgesia was provided by fentanyl and muscle relaxation by atracurium. Anaesthesia was maintained by inhalation of one MAC of either sevoflurane or halothane, based on an equipotent concentration of each agent for the age of the child. Following simultaneous discontinuation of N2O and the inhalational agent, the equation describing N2O washout was identical in the presence of halothane and sevoflurane, showing that there was no effect of the volatile agent on the rate of N2O elimination. The elimination of sevoflurane and N2O give similar types of equations. Halothane elimination gives a logarithmic type of equation, showing a slower release, corresponding to residual tissue content.

Ambulatory Surgical Procedures

Evaluation of tabletop materials for autocontouring in CT treatment planning.

Computerized tomography (CT) treatment planning has been proven to be essential in precision radiotherapy. Typically CT planning requires a large number of CT scans (between 3 and 50 slices) to be entered into the treatment planning system. A significant amount of time in the planning process is devoted to outlining internal structures, organs, and the external patient contour in each CT slice. In principle, external contours could be generated easily using autocontouring routines; however, in reality it does not always provide a satisfactory contour due to the limitations of the CT tabletop having nearly the same CT number as that of the body structure. A solution to this problem is to create a large CT number gradient interface between the patient and CT tabletop by inserting a thin sheet of low CT number material. The optimum material for a tabletop was investigated from a range of low-density and low atomic number media. Various materials were studied by placing them underneath an unsliced humanoid phantom. A portion of the phantom abdomen was imaged and analyzed on a Picker Premier IQ CT scanner. Results indicate that the tabletop should be made of the material that has a CT number at least 10 times lower than the tissue in contact with the table. A simple and cost-effective method of avoiding failures in autocontouring is to place a thin sheet of low-density material such as cardboard or foam board on the tabletop. Such an insert creates a large CT gradient resulting in a significant improvement in the accuracy of the edge detection algorithm used for autocontouring. Detailed analysis is presented.

Algorithms

[Prehospital thrombolysis in the acute phase of myocardial infarction. Apropos of cases handled by the mobile intensive care unit,Argenteuil (Val-d'Oise) from 1988 to 1991].

We have studied prehospital thrombolytic therapy in acute myocardial infarction administered by the mobile intensive care unit of the Argenteuil hospital (Val d'Oise), between 1988 and 1991, after having detailed the protocol used. Our results confirm the effectiveness of thrombolysis, showing a rapid improvement of pain and ST segment in 50% of cases. There is a significant saving of time between pain and thrombolysis when the treatment is started during the prehospital phase. At present, in accordance with Isis 3 study results, Streptokinase is the drug of choice with rtPA being reserved for cases with contraindications for Streptokinase.

Adult

Post-herniorrhaphy urinary retention: a randomized prospective study.

Urinary retention is a known complication of inguinal herniorrhaphy. Bladder distension due to vigorous fluid administration is believed to contribute to this problem. Our hypothesis is that fluid restriction will lower the incidence of urinary retention, post-herniorrhaphy. From January 1989 through March 1991, 113 male patients entered the study. Sixty patients (Group I) received unlimited iv fluids (1294 +/- 58 ml) and 9 patients (15%) developed urinary retention. Fifty-three patients (Group II) received 500 ml or less by protocol (485 +/- 2 ml) and 5 of these patients developed retention (9%). Thus, fluid restriction lowered the incidence of urinary retention post-herniorrhaphy but the difference did not reach statistical significance. In addition age over 60 years approached significance as a risk factor for postoperative urinary retention.

Aged

Antigenic cross-reactions among immunoglobulin of diverse vertebrates (elasmobranchs to man) detected using xenoantisera.

1. Antisera raised in rabbits and goats against intact immunoglobulins or their constituent light and heavy chains from man, mouse and the galapagos shark (Carcharhinus galapagenesis) were tested for their reactivity with immunoglobulins of elasmobranchs, other lower vertebrates and eutherian and prototherian mammals. 2. Xenoantisera directed against human heavy chain isotypes allowed the serological identification of IgM and IgG immunoglobulins in the echidna (Tachyglossus aculeatus), a monotreme which is one of the most primitive species of extant mammals. 3. The antisera to heavy chains reacted to varying degrees with purified immunoglobulins of non-mammalian species, including the chicken, teleost fish and elasmobranchs in a fashion that was specific for immunoglobulins, but was not related to defined human isotypic markers. 4. The reactions of some antisera seem to skip species known to possess homologous immunoglobulins. 5. Antisera directed against isotypic markers of human kappa and lambda light chains reacted with shark light chains in a manner that was specific for light chain determinants but was not isotype-related. 6. Antisera directed against heavy chains of either sharks or mammals reacted with heavy chains, but not with light chains of diverse species. 7. A rabbit antiserum specific for shark light chain reacted with human and murine monoclonal lambda chains and with two synthetic peptides corresponding to human V lambda Fr3 and Fr4 sequences. 8. These results establish that a variety of antigenic markers including conformational and linear determinants can be shared among immunoglobulins of vertebrates species that had an ancestral divergence more than 400 million years ago.

Amino Acid Sequence

Hemodynamic and catecholamine response to isoflurane versus droperidol in complement to fentanyl anaesthesia.

Droperidol (0.03 mg.kg-1 to 0.25 mg.kg-1) with fentanyl has been reported to be less efficient than volatile agents in the prevention of haemodynamic responses to surgery. The aim of this study was to investigate the use of high-dose droperidol in complement to fentanyl in comparison with isoflurane and fentanyl anaesthesia. Thirty patients undergoing laryngectomy were studied. Systolic blood pressure (SBP), heart rate (HR) and plasma catecholamines were analysed both during anaesthesia and during recovery. During surgery, SBP epinephrine (E) levels did not change in either group. HR was slightly lower during droperidol fentanyl anaesthesia. Norepinephrine (NE) levels were significantly higher in the droperidol group than in the isoflurane group (P less than 0.05). During recovery, in both groups, SBP increased by 20% whereas E levels increased by 65%. NE levels increased post-operatively in both groups, but this rise was significantly higher in the droperidol group (P less than 0.01). It is concluded that the two techniques contribute to the haemodynamic stability during surgery, but do not prevent haemodynamic instability during recovery.

Anesthesia, General

Carbon dioxide monitoring during high frequency jet ventilation for direct laryngoscopy.

To improve ventilation monitoring during direct laryngoscopy, we have developed a high frequency jet ventilator which allows the aspiration of tracheal gas for carbon dioxide analysis (PtCO2) through the injector after stopping the ventilator. In 41 patients undergoing direct laryngoscopy, PaCO2 and PtCO2 were measured simultaneously during high frequency jet ventilation under general anaesthesia. PtCO2 and PaCO2 correlated significantly (r = 0.88), but PtCO2 underestimated PaCO2 by 0.84 (SD 0.72) kPa. The arterial to tracheal PCO2 difference was influenced by airway obstruction.

Anesthesia, General

Failure to find Ca2(+)-dependent proteinase (calpain) activity in a plant species, Elodea densa.

Five and nine-tenth kg of Elodea densa (Anacharis), a common aquarium plant, was extracted, and the extract was subjected to column chromatographic procedures that successfully purify the two Ca2(+)-dependent proteinases (calpains) and their protein inhibitor (calpastatin) from a variety of animal tissues. Although these procedures purified a protein having 55- and 16-kDa polypeptides, neither this protein nor any of the other chromatographic fractions contained detectable proteinase or calpastatin activity. Moreover, the purified 55- and 16-kDa polypeptides did not react on immunoblots with polyclonal antibodies that were monospecific for the calpains or calpastatin. We conclude that Elodea densa contains no calpain nor calpastatin at the level of 4 micrograms per g plant protein (1 part per 250,000), which was the sensitivity of our assay.

Actins