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Biomedical subjects

C R MacKenzie

Publications and source records attributed to C R MacKenzie.

At least 73 records · Page 4Linked to original sources
PubMed1991

Risk for postoperative congestive heart failure.

To identify predictors of postoperative congestive heart failure (CHF), a high-risk population, mainly hypertensive and diabetic patients undergoing elective general operations, was studied. Of the 254 patients, 6 per cent had postoperative CHF. Among patients with preoperative cardiac disease (that is, previous myocardial infarction, valvular disease or CHF), 17 per cent had postoperative CHF; in contrast with less than 1 per cent of those without cardiac disease (p less than 0.001). Patients with diabetes were also at high risk (12 versus 2 per cent, p less than 0.005), particularly those with cardiac disease. Patients who had equal to or greater than 40 millimeters of mercury increases or decreases intraoperatively in mean arterial pressure in relation to preoperative baseline had increased postoperative failure rates (p less than 0.02). Of note, postoperative failure rates were highest among patients with less than 500 milliliters per hour of net intake (input and output) (p less than 0.03). Risk for postoperative CHF was restricted to patients with preoperative symptomatic cardiac disease and was especially high if patients also had diabetes. Intraoperative fluctuations in mean arterial pressure increased the probability of postoperative failure, while the intraoperative administration of higher net volumes of fluid was associated with decreased risk.

Aged↗
PubMed1990

Synthesis and expression in Escherichia coli of DNA encoding the murine lambda 1 chain of a monoclonal antibody specific for Salmonella serotype B O-antigen.

A 658 bp DNA sequence corresponding to the murine lambda 1 chain of a monoclonal antibody, Se155-4, specific for the Salmonella serotype B O-antigen, was designed using Escherichia coli preferred codons and chemically synthesized by ligation of synthetic fragments into a linearized plasmid followed by transformation into E. coli. A synthetic signal peptide (ompA) was fused to express the L chain as a free polypeptide into the periplasm of E. coli cells. After isolation and purification, heterologous recombination of the E. coli L chain with mouse H chain gave an active antigen-binding protein. The activity was 15-20% when compared to protein created by an equivalent association of isolated natural mouse L and H chains as measured by a direct EIA assay. In inhibition experiments with the polysaccharide antigen, the two proteins showed identical titration curves and 50% inhibition points, indicating comparable KA values.

Amino Acid Sequence↗
PubMed1990

Preoperative characteristics predicting intraoperative hypotension and hypertension among hypertensives and diabetics undergoing noncardiac surgery.

We prospectively studied patients with hypertension and diabetes undergoing elective noncardiac surgery with general anesthesia to test the hypothesis that patients at high risk for prognostically significant intraoperative hemodynamic instability could be identified by their preoperative characteristics. Specifically we hypothesized that patients with a low functional capacity, decreased plasma volume, or significant cardiac comorbidity would be at high risk for intraoperative hypotension and those with a history of severe hypertension would be at risk for intraoperative hypertension. Patients who had a preoperative mean arterial pressure (MAP) greater than or equal to 110, a walking distance of less than 400 m, or a plasma volume less than 3000 cc were at increased risk of intraoperative hypotension (i.e., more than 1 hour of greater than or equal to 20 mmHg decreases in the MAP). Hypotension was also more common among patients having intra-abdominal or vascular surgery, and among those who had operations longer than 2 hours. Patients older than 70 years or with a decreased plasma volume were at increased risk of having more than 15 minutes of intraoperative elevations of greater than or equal to 20 mmHg over the preoperative MAP in combination with intraoperative hypotension; this was also more common when surgery lasted more than 2 hours. Patients who had intraoperative hypotension tended to have an immediate decrease in MAP at the onset of anesthesia and were often purposefully maintained at MAPs less than their usual level during surgery with fentanyl and neuromuscular blocking agents. Patients who had intraoperative hyper/hypotension tended to have repeated elevations in MAP above their preoperative levels during the course of surgery, and such elevations precipitated interventions with neuromuscular blocking agents and/or fentanyl. Neither pattern was more common among patients who developed net intraoperative negative fluid balances. Both hypotension and hyper/hypotension were associated with increased renal and cardiac complications after operation. Patients with cardiac disease, especially diabetics, and those with negative fluid balances also had increased complications. Preoperative characteristics influence the susceptibility to intraoperative hypotension and hypertension, which are related to postoperative complications.

Aged↗
PubMed1990

Intraoperative blood pressure. What patterns identify patients at risk for postoperative complications?

While monitoring blood pressure is a routine part of intraoperative management, several methods have been proposed to characterize intraoperative hemodynamic patterns as predictors of postoperative complications. In this prospective study of a high-risk population of hypertensive and diabetic patients undergoing elective noncardiac surgery, one objective was to compare different approaches to the assessment of intraoperative hemodynamic patterns to identify those patterns most likely to be associated with postoperative complications. Twenty-one per cent of the 254 patients sustained cardiac or renal complications after operation. Patients with more than 1 hour of greater than or equal to 20-mmHg decreases in mean arterial pressure (MAP) or patients with less than 1 hour of greater than or equal to 20-mmHg decreases and more than 15 minutes of greater than or equal to 20-mmHg increases were at highest risk for postoperative complications. Together these two patterns had a 46% sensitivity rate and a 70% specificity rate in predicting postoperative complications. Using 20% change in intraoperative MAP produced results nearly identical to 20-mmHg changes. When the duration of 20-mmHg changes was accounted for, changes of a greater magnitude (e.g., 40 mmHg) were not significant independent predictors of complications. The use of the mean difference from preoperative MAP was misleading because patients who experienced both high and low MAPs tended to have nearly normal mean MAPs, but high complication rates. The absolute magnitude of intraoperative MAPs, regardless of the preoperative levels, also was evaluated. The overall mean intraoperative MAP was not a significant predictor of complications. Specific intraoperative MAPs (e.g., less than 70 mmHg and more than 120 mmHg) also were evaluated. While neither was a significant predictor, there was a trend for increased complications among patients whose MAPs decreased to less than 70 mmHg. Intraoperative blood pressure should be analyzed in relation to the patient's preoperative blood pressure. Prolonged changes of more than 20 mmHg or 20% in relation to preoperative levels were significantly related to complications.

Blood Pressure↗
PubMed1990

Purification and properties of an acetylxylan esterase from Fibrobacter succinogenes S85.

An acetylxylan esterase (EC 3.1.1.6) was purified to apparent homogeneity from the nonsedimentable extracellular culture fluid of Fibrobacter succinogenes S85 grown on cellulose. This enzyme had an apparent molecular mass of 55 kDa and an isoelectric point of 4.0. The temperature and pH optima were 45 degrees C and 7.0, respectively. The apparent Km and Vmax were 2.7 mM and 9,100 U/mg, respectively, for the hydrolysis of alpha-naphthyl acetate. The enzyme cleaved acetyl residues from birchwood acetylxylan but did not hydrolyze carboxymethylcellulose, larchwood xylan, ferulic acid-arabinose-xylose polymer, p-nitrophenyl-alpha-L-arab-inofuranoside, or longer-chain naphthyl fatty acid esters. The esterase enzyme may play a role in enhancing hemicellulose degradation by F. succinogenes, thereby allowing it greater access to cellulose present in forage cell walls.

Animals↗
PubMed1989

Identification of three distinct Clostridium thermocellum xylanase genes by molecular cloning.

Three genes coding for xylanase synthesis in Clostridium thermocellum were cloned and expressed in Escherichia coli. Genomic DNA from Clostridium thermocellum was digested to completion with HindIII, BamHI, and SalI. The fragments were ligated into the corresponding sites of pUC19 and transformed into Escherichia coli. Two of the genes encoded for xylanases which depolymerized xylans but were unable to extensively convert these substrates to reducing sugar. The third gene encoded for an enzyme that extensively hydrolyzed xylan. The insert containing the latter gene was subjected to extensive mapping and was found to encode for a xylanase with a molecular weight of approximately 25,000. The protein product of the cloned gene was obtained in a relatively pure form by heat treatment, ion exchange and gel permeation steps. The enzyme was quite stable to high temperatures with a half-life of 24 h at 70 degrees C.

Cloning, Molecular↗
PubMed1989

The post-operative electrocardiogram and creatine kinase: implications for diagnosis of myocardial infarction after non-cardiac surgery.

The objective of this study was to evaluate different approaches to the diagnosis of post-operative myocardial infarction. A total of 232 patients, mostly hypertensive and/or diabetic patients, who were undergoing elective non-cardiac surgery were evaluated pre-operatively. They were followed serially from the day of operation to discharge or the sixth post-operative day with daily clinical evaluations, electrocardiograms, creatine kinase and creatine kinase isoenzymes. In total 22% (51/232) of the patients had post-operative ECG changes in two or more leads. Only 1% developed new Q waves; most of the changes involved changes in the T or ST segments. Seventy percent of patients who had changes in their electrocardiogram were completely asymptomatic. The highest risk of ECG changes or symptoms occurred on the day of operation and the first post-operative day; evidence of post-operative infarction was infrequent after the second post-operative day. Creatine kinase levels rose an average of 250-300 IU on the first and second post-operative day (also the peak time for post-operative ECG changes), reducing its utility as an adjunct to the diagnosis of post-operative infarctions. Importantly, 52% (12/23) of the patients who had greater than or equal to 5% MB isoenzyme had neither ECG changes nor symptoms; the diagnosis of a myocardial infarction should not be made in these patients. In summary, most patients who experience ischemia or infarction post-operatively are asymptomatic. Symptoms should not be required for the diagnosis of post-operative infarction. Seemingly minor differences in criteria can produce major discrepancies in post-operative myocardial infarction rates (from 1 to 9%). The development of a final set of criteria will require further study but the diagnosis of post-operative infarction should probably be based on ECG changes, their duration and consistency, and the association of a positive MB fraction.

Aged↗
PubMed1989

Postoperative changes in serum creatinine. When do they occur and how much is important?

The objective of this study was to evaluate the use of the serum creatinine in following postoperative renal function. In this prospective study of 278 patients (mainly hypertensives and diabetics) undergoing noncardiac surgery, the serum creatinines were followed from the first through the sixth postoperative day. Creatinine clearances were evaluated before operation and on the fourth to fifth postoperative day. During the first six days after the operation, 23% (65 of 278 patients) had an increase of serum creatinine greater than or equal to 20%. Such increases were sustained for greater than or equal to 48 hours in 12% of the patients (32 of 278), and half of these patients had not returned to their initial level of renal function by the time of discharge. Patients who sustained such a deterioration were at risk for nonoliguric renal failure if they had a subsequent insult (i.e., hypotension, reoperation, angiography, aminoglycosides). Such increases occurred early in the postoperative period--on the first or second postoperative day. As judged by the creatinine clearances, postoperative increases of greater than or equal to 20% in the serum creatinine identified most patients whose clearance fell more than 50%, although the serum creatinine did not accurately reflect changes in creatinine clearance among those patients who had undergone an amputation. It is concluded that the serum creatinine is useful in monitoring postoperative renal function. Of those patients who had postoperative increases in serum creatinine sustained for greater than or equal to 48 hours, as many as one third had evidence of impairment in renal function at the time of discharge.

Acute Kidney Injury↗
PubMed1989

The preoperative and intraoperative hemodynamic predictors of postoperative myocardial infarction or ischemia in patients undergoing noncardiac surgery.

Among hypertensive and diabetic patients undergoing elective noncardiac surgery, preoperative status and intraoperative changes in mean arterial pressure (MAP) were evaluated as predictors of postoperative ischemic complications. Of 254 patients evaluated before operation and monitored during operation, 30 (12%) had postoperative cardiac death, ischemia, or infarction. Twenty-four per cent of patients with a previous myocardial infarction or cardiomegaly had an ischemic postoperative cardiac complication. Only 7% of those without either of these conditions sustained an ischemic complication. No other preoperative characteristics, including the presence of angina, predicted ischemic cardiac risk. Nineteen per cent of patients who had 20 mm Hg or more intraoperative decreases in MAP lasting 60 minutes or more had ischemic cardiac complications. Patients who had more than 20 mm Hg decreases in MAP lasting 5 to 59 minutes and more than 20 mm Hg increases lasting 15 minutes or more also had increased complications (p less than 0.03). Changes in pulse were not independent predictors of complications and the use of the rate-pressure product did not improve prediction based on MAP alone. In conclusion patients with a previous infarction or radiographic cardiomegaly are at high risk for postoperative ischemic complications. Prolonged intraoperative increases or decreases of 20 mm or more in MAP also resulted in a significant increase in these potentially life-threatening surgical complications.

Adult↗
PubMed1989

Identification of two distinct Bacillus circulans xylanases by molecular cloning of the genes and expression in Escherichia coli.

Two genes coding for xylanase synthesis in Bacillus circulans were cloned and expressed in Escherichia coli. After digestion of genomic DNA from Bacillus circulans with EcoRI and PstI, the fragments were ligated into the corresponding sites of pUC19 and transformed into Escherichia coli. Restriction enzyme mapping of the two inserts coding for xylanase activity indicated distinctly different nucleotide sequences. Cross-hybridization assays confirmed the absence of sequence homology between the two genes. In vitro transcription-translation assays indicated that the cloned genes encoded for proteins with molecular weights of 22,000 and 59,000. The gene products displayed different substrate specificities. The 22,000-dalton enzyme readily hybrolyzed aspeen, larchwood, and oat spelt xylans, whereas the second was unable to extensively depolymerize oat spelt xylan and resulted in very limited reducing sugar release from any of the xylan substrates tested. Both of the xylanases had isoelectric points of approximately 9.0.

Bacillus↗
PubMed1989

Hyperexpression of a Bacillus circulans xylanase gene in Escherichia coli and characterization of the gene product.

A 4.0-kilobase (kb) fragment of Bacillus circulans genomic DNA inserted into pUC19 and encoding endoxylanase activity was subjected to a series of subclonings. A 1.0-kb HindIII-HincII subfragment was found to code for xylanase activity. Maximum expression levels were observed with a subclone that contained an additional 0.3-kb sequence upstream from the coding region. Enhancer sequences in the upstream region are thought to be responsible for these high expression levels. Southern hybridization analyses revealed that the cloned gene hybridized with genomic DNA from Bacillus subtilis and Bacillus polymyxa. Xylanase activity expressed by Escherichia coli harboring the cloned gene was located primarily in the intracellular fraction. Levels of up to 7 U/ml or 35 mg/liter were obtained. The protein product was purified by ion exchange and gel permeation chromatography. The xylanase had a molecular weight of 20,500 and an isoelectric point of 9.0.

Bacillus↗
PubMed1989

Postoperative renal dysfunction can be predicted.

The two prior hypotheses of the study were that, among a high risk population of patients who were hypertensive, who had diabetes and who underwent elective general surgical treatment, the duration of intraoperative hypotension and hypertension (greater than 20 millimeters of mercury above or below the preoperative base line) and intraoperative administration of less than 300 milliliters per hour of saline solution containing fluids would identify patients at higher risk for postoperative renal dysfunction. Among those who had an intraoperative mean arterial pressure (MAP) that fell more than 20 millimeters of mercury below the base line, 15 per cent of those with fall of MAP lasting for greater than or equal to 60 minutes had postoperative renal dysfunction, whereas those with drops in pressure lasting for less than 60 minutes did not sustain increased postoperative renal dysfunction. Patients who had intraoperative MAP rise to greater than 20 millimeters of mercury above the preoperative base line value for greater than 30 minutes also had twice the rate of postoperative renal dysfunction. Fifteen per cent of the patients who received less than 300 milliliters per hour of isotonic saline-like fluids had postoperative renal dysfunction, significantly more than the 8 per cent of those who received greater than or equal to 300 milliliters per hour. Two intraoperative events also significantly increased postoperative renal dysfunction rates: cardiac arrest and the drainage of massive ascites. Patients with decompensated congestive heart failure at admission to the hospital had significantly increased postoperative renal dysfunction; these patients and probably should not undergo an operation unless it is an emergency. All of the patients, regardless of the magnitude of the operation and of its projected length or type of anesthesia, should be given greater than 300 milliliters per hour of isotonic saline-like solutions.

Aged↗
PubMed1988

Trade-offs between hospital charges and patient outcomes.

The increasing cost of health care has focused attention on the trade-offs between health care expenditures and patient outcomes. In this study, hospital charges were contrasted with the health status at 1 year of follow-up of 549 patients admitted to a university hospital medical service. The findings related to short-term outcomes were consistent with those of other investigators: large expenditures were associated with patients who died in the hospital, especially those whose death was unexpected. Both 1-year survival and hospital charges were found to correlate with physician estimates of illness severity and prognosis at the time of admission. Patients considered not ill with a favorable prognosis had a mortality rate at 1 year of 3%, comprised 7% of the cohort and generated 2% of total charges. In contrast, patients considered severely ill with an unfavorable prognosis had a mortality rate of 65%, comprised 19% of the cohort and generated 30% of total charges. Nevertheless, 46% of the survivors in this latter group were considered to be functional and only mildly ill at 1 year of follow-up. The imprecision of clinical judgements at the time of admission in predicting long-term outcome argues for aggressive management of acutely hospitalized patients when there is any doubt about their prognosis.

Fees and Charges↗
PubMed1988

Surveillance for postoperative myocardial infarction after noncardiac operations.

Patients with postoperative myocardial infarction are frequently asymptomatic. Several follow-up strategies have been used to detect infarction or ischemia in asymptomatic patients. Different investigators have used quite different criteria to define patients at high risk. This study was done to evaluate these different approaches to selecting patients who should be monitored with electrocardiograms (ECG) or enzymes, or both, postoperatively, as well as different strategies for the timing of follow-up evaluation. A total of 232 patients, mostly hypertensive or diabetic, were evaluated before undergoing elective operations and were observed serially from the day of the operation until discharge or the sixth postoperative day with daily clinical evaluations, ECG and creatine kinase isoenzymes. Several follow-up strategies used in recent studies were evaluated for sensitivity and specificity in identifying the patient who had postoperative infarctions or ischemia. The most sensitive strategies would obtain ECG in asymptomatic patients on the day of the operation and the first two postoperative days. Several criteria for defining a high risk population were evaluated, including type of operation, age, history of cardiac disease, Goldman's cardiac risk classification and the results of the preoperative ECG. Monitoring of patients with an abnormal preoperative ECG would have identified 88 per cent of the patients with postoperative myocardial infarction and 63 per cent of the patients with definite ischemia. Goldman's risk class identified patients with a normal ECG who were at higher risk for postoperative ischemia.

Adult↗
PubMed1988

Assessment of perioperative risk in the patient with diabetes mellitus.

To define the preoperative clinical characteristics that identify patients with diabetes mellitus at increased risk for postoperative complications, and inception cohort of diabetic patients undergoing surgical treatment was examined. Serious cardiac morbidity and death were predicted by the presence of pre-existing cardiac disease, specifically, congestive heart failure and valvular heart disease. Patients at increased risk for non-cardiac complications (infection, renal insufficiency and cerebral ischemic events) included 24 per cent of those patients with diabetic end-organ disease (retinopathy, neuropathy and nephropathy), 29 per cent of those with congestive heart failure or valvular heart disease and 35 per cent of those with peripheral vascular disease and infection. In patients who did not have such pre-existing conditions, serious noncardiac complications were rare (4 per cent). Neither the severity of the disease nor the degree of perioperative glucose control were associated with increased postoperative morbidity or mortality. We conclude that, among patients with diabetes mellitus who are undergoing surgical procedures, postoperative complications can be predicted by the presence of readily identifiable preoperative clinical characteristics.

Adult↗
PubMed1987

Morbidity during hospitalization: can we predict it?

Physicians use the concept of stability to estimate the likelihood that a patient will deteriorate during a hospitalization. To determine whether physicians can accurately predict a patient's risk of morbidity, 603 patients admitted to the medical service during a one month period were rated prospectively as to how stable they were. Overall, 15% of patients had deterioration of already compromised systems, while 17% had new complications, such as sepsis. Eight percent of patients had both. Twelve percent of stable patients experienced morbidity; 39% of the somewhat unstable and 61% of the most unstable. When all of the demographic and clinical variables were taken into account including the reason for admission and comorbid diseases, the residents' estimates of the patient's stability was the most significant predictor of morbidity (p less than 0.001). The judgment that a patient was stable had an 87% negative predictive accuracy, while the judgment unstable had a 46% positive predictive accuracy.

Aged↗
PubMed1987

A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.

The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.

Actuarial Analysis↗