Vomiting after alfentanil anesthesia.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Patel.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
No study has elucidated the minimum time taken for oxygen delivery to reach steady-state levels after an increase in positive end-expiratory pressure (PEEP). We therefore investigated ten ventilated patients who received a total of 27 increments in PEEP of 5 cm H2O. Cardiorespiratory parameters were measured at baseline, at 1 min, and thereafter at 5-min intervals until 2 consecutive measurements of oxygen delivery were constant. Cardiac output was measured continuously using an esophageal Doppler transducer. The PEEP was increased to a maximum of 20 cm H2O or until oxygen delivery fell by 15 percent. Increases in PEEP were always associated with increases in oxygen saturation. Cardiac output decreased in the majority of cases, the greatest falls occurring in the first minute after an increase in PEEP, and with higher levels of PEEP. No significant changes in oxygen delivery occurred after 15 min. We therefore recommend that 15 min be allowed to elapse after an increase in PEEP before oxygen delivery is reassessed.
Reliability of the maximal inspiratory pressure (Pimax) was examined by measuring Pimax once a week for 4 weeks in 91 patients with chronic obstructive pulmonary disease using an aneroid pressure gauge. Five Pimax trials were conducted at each test. From the first to the fourth test, the Pimax increased by a mean of 9 cm H2O (SD = 10). From the third to the fourth test, Pimax increased by a mean of 2 cm H2O and performance appeared to be plateauing. The test-retest reliability coefficient was r = 0.97 for Pimax measured at the third and fourth test session. The 95 percent confidence interval for the absolute difference in Pimax at the third and fourth test was 3 to 5 cm H2O. We conclude that performance of Pimax improves with practice in naive COPD patients and Pimax is reliable when measured with an aneroid gauge by experienced data collectors if patients are given sufficient practice.
OBJECTIVE: To determine the age- and sex-specific prevalence of diabetes and to examine associations between related anthropometric and metabolic abnormalities in an Aboriginal community in central Australia with a long history of acculturation. RESEARCH DESIGN AND METHODS: We used a cross-sectional survey of 353 adults > 15 yr of age (87% response rate) and measured the following parameters: weight, height, circumferences of waist and hips; glucose, insulin, cholesterol, triglyceride, and high-density lipoprotein cholesterol in fasting plasma; and plasma glucose and insulin 2 h after 75 g oral glucose. RESULTS: The prevalence of diabetes was 29.6% in survey participants > 35 yr of age and 5.3% in those < 35 yr of age. Impaired glucose tolerance also occurred with higher frequency in those > 35 yr of age (14.8 vs. 4.7%). Of those > 35 yr of age, 75% of the women and 51% of the men were overweight or obese, with a body mass index > or = 25 kg/m2. A large insulin response to oral glucose was evident, with the upper tertile of the 2-h insulin response six times higher than the lower tertile (113 +/- 43 vs. 19 +/- 8 mU/L). Hyperinsulinemia showed a strong, positive association with impaired glucose tolerance, body mass index, waist-to-hip ratio, cholesterol, and triglyceride levels and a negative association with high-density lipoprotein cholesterol levels. Cholesterol levels were on average 0.5 mM higher in men than in women. Deteriorations in carbohydrate and lipid metabolism occurred before 40 yr of age: diabetes, body mass index, waist-to-hip ratio, and fasting triglycerides and cholesterol concentrations peaked and high-density lipoprotein cholesterol concentrations reached their nadir at the end of the fourth decade. CONCLUSIONS: These data suggest that any intervention programs developed to prevent or reduce diabetes prevalence in this population should be targeted at adolescents and young adults.
From November 1990 to June 1991 33 acute cases of melioidosis occurred in the Northern Territory, Australia; 25 cases were reported in the capital city, Darwin. We carried out an epidemiological investigation to exclude a common source outbreak, describe the risk factors for disease, and develop and institute appropriate control measures. We compared population based attack rates among various risk groups using logistic regression, and the demographic, medical and behavioral risk factors for melioidosis by a matched case-control study. Environmental Health Officers collected soil, surface water and cooling tower water specimens for Pseudomonas pseudomallei culture. The crude attack rate of melioidosis during the outbreak was 52 per 100,000. Age, gender, race, diabetes and alcohol abuse were independent risk factors for disease. The relative risk of disease in diabetic patients was 12.9 (95% CI 5.1-32.7; p < 0.001) and 6.7 in alcoholic patients (95% CI 2.9-15.2; p < 0.001). We found no significant difference between cases and controls in matched pair analysis for any of several exposure factors studied. We isolated Pseudomonas pseudomallei from 4% of soil samples and 9% of surface water samples. Our study confirms the importance of host factors in the development of melioidosis, and attempts to quantify the risk of disease during the Darwin epidemic. Pseudomonas pseudomallei is widespread in the soil of urban Darwin.
Explore the source record for details and available documents.
Twelve cases of endodermal sinus tumor were reviewed. There were 10 females and 2 males with a median age at presentation of 3 years. The primary site was sacrococcygeal in 4 patients, vaginal in 3, retroperitoneal in 2, and testicular, ovarian and left chest wall in one each. The diagnosis rested on histopathological examination and elevation of serum alfa feto protein levels (median 46,200 ng/ml). Two patients had Stage I disease, 9 had Stage III and one had Stage IV disease. Patients were managed by surgery and chemotherapy (BVP regime). All patients on BVP (even those lost at later stages), had achieved clinical remission with the first cycle of treatment.
Cold-reactive antibodies may cause peripheral ischaemia, occasionally proceeding to gangrene on exposure to cold. A 46-year-old male with syphilis, presented with an unusual combination of both paroxysmal cold haemoglobinuria and cold agglutinin disease, resulting in peripheral gangrene and requiring bilateral below knee amputations.
Murine CTL have seven serine proteases, known as granzymes, in their lytic granules. Despite considerable effort, convincing evidence that these enzymes play an obligatory role in the lytic process has not been presented. To investigate the function of one of these proteases, granzyme A (GA), we utilized an antisense expression vector to lower the level of the enzyme in the cells. An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1. Transfectants were selected based on resistance to hygromycin B, and a number of stable lines were developed. One of the antisense lines had greatly reduced levels of GA mRNA, when compared to the parental cells or to control lines transfected with the vector lacking the antisense DNA. The message levels for two other CTL granule proteins, granzyme B and perforin, were unaffected by the antisense vector. The amount of GA, as measured by enzymatic activity, was 3- to 10-fold lower in the transfectant. Most significantly, this line also consistently showed 50 to 70% lower ability to lyse nucleated target cells and to degrade their DNA. Furthermore, it exhibited 90 to 95% lower lytic activity to anti-CD3-coated SRBC. Conjugate formation with target cells, however, was normal. These data provide strong evidence that GA plays an important role in the cytolytic cycle, and that the quantity of enzyme is a limiting factor in these cytolytic cells.
A diuretic peptide (Periplaneta-DP) has been isolated from extracts of whole heads of the cockroach, Periplaneta americana. The purified peptide increases cyclic AMP production and the rate of fluid secretion by isolated Malpighian tubules in vitro. In the fluid secretion assay, the response to native Periplaneta-DP is comparable to that obtained with crude extracts of cockroach corpora cardiaca, and the EC50 lies between 10(-8) and 10(-9) M. The primary structure of Periplaneta-DP was established as a 46-residue amidated peptide: T G S G P S L S I V N P L D V L R Q R L L L E I A R R R M R Q S Q D Q I Q A N R E I L Q T I-NH2. Periplaneta-DP is a further member of the recently established family of CRF-related insect diuretic peptides.
1. 2-(N'-Acetyl-D-phenylalanyl)hydroxyethyl 2'-pyridyl disulphide (compound IV) (m.p. 59 degrees C; [alpha]D20 -6.6 degrees (c 1.2 in methanol)) was synthesized. 2. The results of a study of the pH-dependence of the second-order rate constant (k) for its reaction with the catalytic-site thiol group (Cys-25) of papain (EC 3.4.22.2) together with analogous kinetic data for the reactions of related time-dependent inhibitors, notably the L-enantiomer of compound (IV) (compound III) and the L- and D-enantiomers of 2-(N'-acetylphenylalanylamino)ethyl 2'-pyridyl disulphide (compounds I and II respectively), were used to assess the contributions of the (P1)-NH ... O = C < (Asp-158) and (P2) > C = O ... H-N-(Gly-66) hydrogen bonds and enantiomeric P2-S2 hydrophobic contacts in two manifestations of dynamic molecular recognition in papain-ligand association: (a) signalling to the catalytic-site region to provide for a (His-159)-IM(+)-H-assisted transition state and (b) the dependence of P2-S2 stereoselectivity on hydrogen-bonding interactions outside the S2 subsite. The analysis involved determination of the reactivities of individual ionization states of the reactions (pH-independent rate constants, k) and associated macroscopic pKa values and difference kinetic specificity energies (delta delta GKS = -RT1n(k1/k2), where k1 is the pH-independent second-order rate constant for reaction with one inhibitor and k2 is the analogous rate constant in the same ionization state for reaction with another inhibitor so that, when the structural change provides that k2 > k1, delta delta GKS is positive. 3. The kinetic data further illuminate the nature of the interdependence of binding interactions in papain first noted by Kowlessur, Topham, Thomas, O'Driscoll, Templeton & Brocklehurst [(1989) Biochem. J. 258, 755-764] in the S2 subsite, S1-S2 intersubsite and catalytic-site regions. Of particular note is the apparent dependence of the binding of the N-Ac-D-Phe moiety on the binding of the leaving group to (His-159)-Im+H and the fact that the resulting rate enhancement is more effective when (P1)-N-H is absent than when it is present. This result revealed by kinetic analysis goes beyond the conclusion suggested by model building that it is possible to make all of the binding contacts in complexes involving the D-enantiomers [(II) and (IV)] as in those involving the L-enantiomers [(I) and (III)].(ABSTRACT TRUNCATED AT 400 WORDS)
We have previously reported that lipopolysaccharide (LPS) binding protein (LBP) opsonizes endotoxin (LPS) for recognition by CD14 on phagocytes. Here we show that normal human plasma contains high titers of an activity that also binds LPS (Re, 595) and mediates recognition by CD14. Opsonization of LPS-coated particles with plasma enables the particles to be bound by phagocytes. Further, opsonization with plasma also enables subnanogram-per-milliliter concentrations of LPS to induce dramatic alterations in the function of leukocyte integrins on polymorphonuclear leukocytes and to induce secretion of tumor necrosis factor by monocytes, suggesting that opsonization by factors in plasma may be important in responses of cells to endotoxin. The opsonic activity in plasma appears distinct from LBP since it is not blocked by neutralizing antibodies against LBP. Surprisingly, the opsonic activity of plasma is not present in a single protein species, but at least two species must be combined to observe activity. Further, the opsonic activity of plasma for LPS is blocked by addition of protease inhibitors, suggesting that proteolytic activity or activities are required for opsonization. These properties are suggestive of the action of a protease cascade, but opsonic activity of plasma is not affected by blockade or depletion of either the complement or clotting cascades. We propose the name "septin" to describe this novel LPS-opsonizing activity in plasma.
L-Glutamate and L-cystine appeared to compete for transport via a mediated Na(+)-independent transport process in 1- and 2-cell conceptuses. Not only did these substances competitively inhibit each others' uptake by conceptuses, but their Ki values for inhibition were about equal to their Km values for transport in 1-cell conceptuses. Moreover, the transport process interacted strongly with L-amino acids that had 3-6 atoms in a chain between their negatively charged groups, whereas it interacted weakly or not at all with amino acids that did not have these characteristics or that were N-methylated. Transport of anionic amino acids was not altered greatly by pH in the range 4.5-8.0, but transport of L-cystine was much faster at higher pH values. The slower cystine transport at lower pH values was due primarily to protonation of its second amino group. A small increase in the degree of deprotonation of cystine's carboxyl groups also probably contributed slightly to its faster transport at higher pH values. By all of these criteria, the transport process in conceptuses appears to be a form of amino acid transport system xc-. System xc- activity was several-fold higher in 1- than in 2-cell conceptuses. Similarly, L-glutamate uptake by unfertilized eggs was relatively rapid, whereas it was much slower in immature, fully-grown oocytes. System xc- activity in 1-cell conceptuses also appeared to increase in response to the oxidative stress of culture, whereas no such increase was observed for 2-cell conceptuses. We suggest that this transient increase in the activity of system xc- activity during development of 2-cell conceptuses from immature, fully-grown oocytes could help protect unfertilized and fertilized eggs from oxidative stresses in situ.
1. Values of the kinetic specificity constant, kcat./Km, for the hydrolysis of N-acetyl-L-phenylalanylglycine 4-nitroanilide (I) and of its D-enantiomer (II) catalysed by ficin (EC 3.4.22.3) and by actinidin (EC 3.4.22.14) at pH 6.0, I 0.1 mol/l, 8.3% (v/v) NN-dimethylformamide and 25 degrees C were determined by using initial-rate data with [S] much less than Km and weighted nonlinear regression analysis as: for ficin, (kcat./Km)L = 271 +/- 6 M-1.s-1, (kcat./Km)D = 2.9 +/- 0.1 M-1.s-1, and for actinidin (kcat./Km)L = 13.3 +/- 0.7 M-1.s-1, (kcat/Km)D = 0.34 +/- 0.01 M-1.s-1.2. These data and analogous values for the corresponding reactions catalysed by papain (EC 3.4.22.2), (kcat./Km)L = 2064 +/- 31 M-1.s-1, (kcat./Km)D = 5.5 +/- 0.1 M-1.s-1, demonstrate marked variation in stereochemical selectivity for substrates (I) and (II) among the three cysteine proteinases with the following values for the index of stereochemical selectivity Iss = (kcat./Km)L/(kcat./Km)D: for papain, 375; for ficin 93; for actinidin 39. 3. Model building suggests ways in which, for the papain-catalysed reactions, binding interactions involving the extended acyl groups of the substrates may need to change as the reaction proceeds from adsorptive complex (ES) to tetrahedral intermediate (THI) before its rate-determining, general acid-catalysed collapse to acylenzyme intermediate. In particular, satisfactory alignment in the catalytic site at the THI stage of the acylation process appears to demand rotation of the substrate moiety about its long axis. 4. The different consequences of this rotation for the L- and D-enantiomers suggest that for closely related systems the greater the extent of this rotational adjustment the greater would be the value of Iss.5. For the actinidin-substrate combinations, model building suggests that even at the ES complex stage of catalysis it is not possible to approach optimized P2-S2 contacts and the three hydrogen-bonding interactions deduced for papain-ligand complexes in the absence of significant movement of protein conformation. Possible binding modes in which some of the interactions deduced for papain are relaxed are discussed. Consideration of postulated binding modes in the various transition states is shown to account for the order of reactivity reflected in values kcat./Km for the four reactions involving papain (Pap) and actinidin (Act) with the L- and D-enantiomeric substrates: Pap-L much greater than Act-L greater than Pap-D much greater than Act-D.(ABSTRACT TRUNCATED AT 400 WORDS)
Explore the source record for details and available documents.
The arterial grafts currently in use are classified into five basic categories; 10 different commercially available prostheses were chosen to represent these categories. The Vascutek and Bionit are made from knitted Dacron and have medium porosity, requiring preclotting by the surgeon. The DeBakey Soft Woven and Plasma TFE grafts are made from woven Dacron and have low porosity, not requiring preclotting under most circumstances. Also studied were woven and knitted grafts with leakage resistance referred to as "impervious" Dacron grafts: the Vascutek Gelseal, the Bard Albumin Coated DeBakey Vasculour II, the Microvel with Hemashield, and the albumin saturated, autoclaved DeBakey Soft Woven graft. Gore-Tex and Impra are expanded polytetrafluoroethylene grafts which do not require preclotting. For each type, five grafts 6 cm long and 8 mm in diameter were implanted in the descending thoracic aorta of healthy adult dogs for 16 weeks. The physical characteristics, biocompatibility, and healing patterns varied according to the structure and treatment of the grafts. Pretreatment with biomaterials during manufacture is quite effective in preventing transinterstices blood loss during implantation, but results in altered physical qualities, increased thrombogenicity and delayed healing in comparison to the effects of preclotting with autogenous blood at the time of implantation.
Longitudinal elasticities of whole human blood clot, whole canine blood clot, Factor XIII cross-linked fibrin, glutaraldehyde-fixed human albumin, and formaldehyde-fixed collagen, gelatin and collagen/gelatin were determined and normalized to human whole blood clot. Matrices of a knitted Dacron graft were then impregnated with albumin, collagen, and collagen/gelatin and their longitudinal elasticities were determined and normalized to a preclotted graft. Comparisons were also made for the longitudinal elasticities of a virgin graft, a manipulated control for a preclotted graft, and a manipulated control for the matrix-impregnated grafts. Flexibilities were then calculated based on the weights and elasticities of these grafts and normalized to the flexibility of the preclotted graft. Fibrin had twice and 39 times more longitudinal elasticity than human blood clot and collagen, respectively. The preclotted graft has longitudinal elastic properties similar to a virgin graft, and is 2.8, 2, and 1.4 times more elastic than the albumin, collagen and collagen/gelatin grafts, respectively. The preclotted graft was 2.5, 2, and 1.4 times more flexible than the albumin, collagen and collagen/gelatin grafts, respectively.