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C R MacKenzie

Publications and source records attributed to C R MacKenzie.

At least 91 records · Page 5Linked to original sources

Why predictive indexes perform less well in validation studies. Is it magic or methods?

When prognostic indexes have been tested in a second population, they have often performed less well. Since this is believed to be inevitable, methodologic differences that may explain the discrepancies have been overlooked. Data from a prospective study of 232 patients undergoing noncardiac surgery were used to examine the effect of methodologic differences in assembly of population, postoperative surveillance, and the criteria for cardiac complications on the performance of Goldman's cardiac risk index. Our prospective population was used to simulate the methods used in Goldman's study and in three other studies using the risk index to demonstrate the potential impact of differences in population, surveillance, and outcome criteria for cardiac complications. If Goldman's detection and outcome criteria were employed and only the eligibility criteria used for assembly of the populations differed, the overall complication rates would be between 5.2% and 6.9%; and the complication rates for the different Goldman classes were similar. When both different detection strategies and different outcome criteria were used, however, important discrepancies in cardiac complication rates emerged. For example, complication rates in class 2 varied from 2% to 23%. In conclusion, important discrepancies in performance of prognostic indexes may arise from differences in surveillance strategies and definitions of outcome. With sufficient attention to methodologic consistency, the performance of predictive indexes may not inevitably deteriorate in subsequent studies.

Adult↗

Resuscitation: how do we decide? A prospective study of physicians' preferences and the clinical course of hospitalized patients.

Physicians have to address the question of the measures to be employed in the event that a patient's condition deteriorates after admission to the hospital. To identify the information that physicians use in making such decisions, all 604 patients admitted to the medical service during a one-month period were studied. The patient's age and residents' estimates of the patient's long-term prognosis and ability to function were the three primary factors that correlated with intervention preferences. When illness severity, the reason for admission, comorbidity, and poor function were taken into account, mortality and morbidity rates did not differ between patients for whom full vs not-full intervention was favored. Apart from differential rates of admission to critical care units, there were no important differences in the care, course, or mortality of patients for whom less than full intervention was initially favored. Suggestions that physicians should discuss resuscitation with all or most patients who may die are unrealistic. A more prudent strategy is to discuss the issue with patients whose hospital course is marked by a steady deterioration.

Age Factors↗

Standards for the use of ordinal scales in clinical trials.

Ordinal scales are frequently used in clinical trials to quantify outcomes which are non-dimensional. They may be regarded as either single state or transition measures based on whether they assess the outcome at a single point in time or directly examine change which has occurred between two points in time. Each has unique structural and operating characteristics, so that different methodological standards for their construction and utilisation are required. All trials employing ordinal scales published in three leading journals between 1980 and 1984 were examined. For both types of scales the individual ranks must be clearly defined, mutually exclusive, and ordered in a hierarchical progression. Further, both types must be able to detect equally both improvement and deterioration. For this to be ensured with the single state scales the population under study must not be clustered at one extreme of the scale at entry into the trial. With the transition scales internal symmetry must be achieved. Strategies for determining the comparisons to be performed should include emphasis on within patient analysis for crossover trials. Concordance between scale scores and the other measures of outcome employed in the trial must be evaluated. Frequent violations were uncovered in the studies reviewed, and it is hoped that the simple rules outlined will prove useful in the planning and evaluation of future trials.

Classification↗

Cellodextrin utilization and beta-glucosidase production by Bacteroides polypragmatus.

Bacteroides polypragmatus, a mesophilic obligate anaerobe, was shown to simultaneously ferment glucose and cellobiose giving ethanol as a major metabolic end-product. A mixture of higher cellodextrins was also utilized. The bacterium produced a beta-glucosidase with a pI value of 4.2 and a molecular weight of approximately 100,000 daltons. The enzyme was intracellular and functioned optimally at pH 7. The Km values obtained with p-nitrophenyl-beta-D-glucoside and cellobiose as substrates were 0.73 mM and 100 mM, respectively. The enzyme was quite stable at elevated temperatures; in the presence of 10% glycerol (v/v), it had a half-life of 4 h at 55 degrees C. It was also stable during long-term storage at either 4 degrees C or -20 degrees C, provided that 10% (v/v) glycerol was added to preparations maintained at -20 degrees C.

Bacteroides↗

Fermentation of xylose and hemicellulose hydrolysates by an ethanol-adapted culture of Bacteroides polypragmatus.

Bacteroides polypragmatus type strain GP4 was adapted to grow in the presence of 3.5% (w/v) ethanol by successive transfers into 1% (w/v) D-xylose media supplemented with increasing concentrations of ethanol. The maximum specific growth rate of the ethanol-adapted culture (mu = 0.30 h-1) was not affected by up to 2% (w/v) ethanol but that of the non-adapted strain declined by about 50%. The growth rate of both cultures was limited by nutrient(s) contained in yeast extract. The ethanol yield of the adapted culture (1.01 mol/mol xylose) was higher than that (0.80 mol/mol xylose) of the non-adapted strain. The adapted culture retained the ability to simultaneously ferment pentose and hexose sugars, and moreover it was not inhibited by xylose concentrations of 7-9% (w/v). This culture also readily fermented hemicellulose hydrolysates obtained by mild acid hydrolysis of either hydrogen fluoride treated or steam exploded Aspen wood. The ethanol yield from the fermentation of the hydrolysates was comparable to that obtained from xylose.

Bacteroides↗

Can the Sickness Impact Profile measure change? An example of scale assessment.

The Sickness Impact Profile is a well known measure of functional status which has been validated as a measure of differences in function between patients, but not as a measure of within-patient change. To evaluate its performance as a measure of change, the Sickness Impact Profile was compared to a transition index that directly assesses intra-patient differences in maximal physical and emotional function. With the index, patients rate themselves as much better, slightly better, the same, slightly worse or much worse as compared to a previous assessment. When compared to the corresponding index ratings, Sickness Impact Profile subscale score changes for a rating of worse were of greater magnitude than those for a rating of better. The inherent variability of the Sickness Impact Profile score was estimated using the standard deviation of the score change for the index rating "the same". For patients to be regarded as changed they had to lie outside the probability limits of this score change. Defined in this way, only patients who stated they were worse on the index were detected. Receiver operator characteristic curves were constructed and also demonstrated that deteriorations in function were more accurately detected. Using different score cutoffs, the best true positive rate (71%) was obtained using a one point change on the psychosocial subscale. This was accompanied by a 39% false positive rate. No score value appeared sufficiently accurate to be useful. Its apparent inability to detect improvements and deteriorations equally, and the wide standard deviations for a given change in function, may limit the use of the Sickness Impact Profile for following individuals over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Assessing illness severity: does clinical judgment work?

Accurate classification of clinical severity is important for interpreting casemix in clinical studies and for stratifying patients for clinical trials. To evaluate whether clinical judgment might be an effective method of estimating severity, all 604 patients admitted to the medical service in a one month period were rated at the time of admission by the responsible resident as to how sick they were. Within the 13 comorbid disease groups, and within the 15 basic categories of reason for admission, the physicians' severity ratings were the most significant predictor of in-hospital mortality. Death rates rose from 0% in those rated as not ill, to 2% in the mildly ill, to 6% in the moderately ill, to 23% in the severely ill, and to 58% in those rated as moribund (p less than 0.001). Sickness ratings also predicted time to death: mildly ill patients died after prolonged hospitalizations, while the moribund died shortly after admission. The patients' age, sex, race, the number of comorbid diseases or problems did not predict mortality. Patients with serious comorbidity (metastases, AIDS, or cirrhosis) had a higher mortality rate than other patients (p less than 0.001); however, the severity ratings predicted outcomes within this group (p less than 0.001) as well as among those without such serious comorbidity (p less than 0.001). Patients who were admitted with acute neurologic (p less than 0.05) or acute cardiovascular (p less than 0.01) events did have an independently worse prognosis. In conclusion, physicians' estimates or sickness provided an accurate estimate of illness severity, with mortality rates that essentially tripled from one stratum to the next. Clinical judgment may suffice to classify the clinical severity of patients at the time of enrollment in prospective trials and can provide a useful method of controlling for casemix.

Acute Disease↗

Cognitive impairment. Can it predict the course of hospitalized patients?

All patients admitted to three medical services at the New York Hospital during a one-month period were screened with Folstein's Mini-Mental State Examination. The prevalence of cognitive impairment was 19.8% (23 of 116). Cognitively "impaired" patients, ie, those with a Folstein score less than 24, were older, sicker, and less physiologically stable than the cognitively "intact." The in-hospital mortality (17 versus 5%) and morbidity (39 versus 18%) rates were higher for the cognitively "impaired" patients; these differences could be explained by the greater severity of illness, instability, and comorbidity found in these patients. Cognitively "impaired" patients were particularly susceptible to respiratory complications. Cognitively "impaired" patients had longer lengths of hospital stay, spent more time in hospital awaiting placement, and were more likely to be discharged to a nursing home or require home assistance than their cognitively "intact" counterparts. Three-month mortality rates were also higher for the cognitively "impaired" patients (30 versus 15%). These findings suggest that cognitive impairment on admission may be regarded as a marker for patients with poorer prognoses.

Aged↗

A patient-specific measure of change in maximal function.

We designed a short, patient-specific index that measures changes in maximal physical, mental, and emotional function. A baseline component, given at the initial interview, documents the patients' usual activities that require the most physical exertion and mental effort, as well as the patients' ability to cope with stress. A transition component assesses the subsequent change from these patient-specific norms. The index was evaluated in two separate studies involving medical and surgical patients. In the first study, the index was administered twice to 40 patients. Reliability was excellent for all three aspects of function. The transition index had a high degree of internal consistency. In a second study of 43 hospitalized patients, the validity of the index was assessed by comparing its performance with the Sickness Impact Profile; high correlations were found. In addition, the overall patterns of change differed in the expected directions in the medical and surgical groups. This index is unique in its ability to measure change directly, is interpretable in individual patients, and could be easily applied in clinical practice and research.

Activities of Daily Living↗

Reversibility of cognitive impairment in medical inpatients.

To determine outcomes of patients admitted to the hospital with global cognitive impairment and to identify factors that might predict improvement, we screened all medical ward admissions over a one-month period with Folstein's Mini-Mental State Examination. Of 115 patients, 23 (20%) scored less than 24, indicating that they were cognitively impaired. Nineteen patients survived to discharge and were followed up for three months; three additional patients died in this period. Nine (47%) of the 19 patients significantly improved their Mini-Mental State scores. Five (26%) of the 19 improved to normal. They scored better on the initial Mini-Mental State Examination and lower (less dementia) on Blessed's Dementia Rating Scale. Age, severity and stability of medical illness, presence of neurologic abnormalities, clinical course, extensiveness of medical evaluation, and psychiatric criteria for delirium did not predict improvement.

Adult↗

Purification and characterization of an exoglucanase from Streptomyces flavogriseus.

Streptomyces flavogriseus, a mesophilic actinomycete, produces high levels of extracellular enzymes capable of hydrolyzing cellulose and xylan. One such enzyme, an exoglucanase, has been purified to molecular homogeneity by a sequence involving DEAE Bio-Gel A chromatography, gel permeation chromatography on Bio-Gel P-60, preparative isoelectric focusing, and concanavalin A affinity chromatography. This purification sequence disclosed the presence of several distinct endoglucanase and xylanase fractions. Homogeneity of the purified enzyme was demonstrated by analytical isoelectric focusing and sodium dodecyl sulphate--polyacrylamide gel electrophoresis. The purified enzyme had a molecular weight of approximately 45 000 and an isoelectric point of 4.15. The enzyme demonstrated negligible activity with carboxymethylcellulose as the substrate. It was able to extensively hydrolyse acid-swollen cellulose; the main product of enzyme action was cellobiose.

Chromatography, Gel↗

Ampicillin resistance in Neisseria denitrificans: studies on ampicillin-sensitive enzymes.

The beta-lactam sensitivities of enzymes involved in peptidoglycan synthesis were examined in two strains of Neisseria denitrificans having widely disparate degrees of ampicillin sensitivity. One strain of n. denitrificans was 400 times more resistant to ampicillin than the other; the former is known to have altered penicillin-binding proteins. No differences in the levels of sensitivities of total peptidoglycan synthesis as measured by the incorporation of glutamate into peptidoglycan, or of D-alanine carboxypeptidase, were observed between the two strains. However, the rate of glutamate incorporation into peptidoglycan by logarithmic growth phase cells was somewhat less for the ampicillin-resistant cells than for the parent cells.

Ampicillin↗

Antibiotic resistance in Neisseria denitrificans.

An ampicillin-resistant strain of Neisseria denitrificans was produced by serial passage of the organisms in media containing increased concentrations of antibiotic. The 400-fold increase in resistance obtained was a relatively stable characteristic. Ampicillin resistance in this organism was apparently related to a loss or modification of the penicillin-binding proteins associated with the cytoplasmic membranes. Membranes isolated from the ampicillin-resistant strain bound significantly less radioactive penicillin than those isolated from the parent strain and revealed one major and three minor penicillin-binding proteins. All four penicillin-binding proteins were present in reduced amounts or had a decreased capacity for penicillin binding in the ampicillin-resistant cells. The increased resistance did not involve enzymic degradation of the antibiotic or a general reduction in the permeability of the outer layers of the cell. No difference in the amount of peptidoglycan present in the parent and ampicillin-resistant cells or in the gross chemical structure of the peptidoglycans of the two strains was observed.

Ampicillin↗

The syndrome of pneumococcemia, disseminated intravascular coagulation and asplenia.

A 58-year-old man who survived an episode of fulminant pneumococcal septicemia with disseminated intravascular coagulation had undergone splenectomy 23 years previously. In the literature there are 25 reported cases of fulminant septicemia and disseminated intravascular coagulation associated with asplenia in adults (excluding cases in which corticosteroid or immunosuppressive therapy was given). The pneumococcus was responsible for all of these cases as well. The mortality in this series was more than 90%, and death occurred within 24 hours of presentation at hospital in almost 70% of the fatal cases and was associated with high-density bacteremia and adrenal hemorrhage. Gram-staining of the buffy coat of the peripheral blood or the exudate from purpuric skin lesions was carried out in only 6 of the 26 cases but yielded positive results in all but 1. It is concluded that a diagnosis of septicemia in asplenic adults can be established within a short time of presentation on the basis of statistical probability and the results of Gram-staining of the peripheral blood and exudate from the skin lesions. Prevention appears to be the cornerstone of management because of the variable interval from splenectomy to the onset of the syndrome and the high mortality.

Blood Platelet Disorders↗

Glycogen metabolism in the genus Neisseria: synthesis from sucrose by amylosucrase.

Eight strains (seven species) of Neisseria were found to possess intracellular amylosucrases capable of synthesizing glycogen directly from sucrose. All eight systems were stimulated by primer glycogen, possessed similar kinetic parameters, and were competitively inhibited to similar degrees by fructose. The enzymes bound tightly to their polysaccharide products but these complexes could be readily dissociated by polyacrylamide gel electrophoresis. Some of the enzyme-product complexes appeared to be virutally free of contaminating proteins.

Binding, Competitive↗

Surcrose uptake by Neisseria denitrificans.

Neisseria dentrificans possesses an inducible sucrose-uptake system. Sucrose is transported as the free sugar and is rapidly converted into polymerized material. Uptake is inhibited by glucose, cyanide, uncouplers of oxidative phosphorylation, and sulfydryl reagents. Glutamate serves as an energy source for uptake. The importance of this phenomenon in the oral environment is discussed.

Cyanides↗

Structure of the D-glucans produced by Neisseria perflava.

A chemical and enzymic study of the cellular glucan of Neisseria perflava and of the glucan produced from sucrose by a cell-free extract of N. perflava showed from optical rotation, 13C nuclear magnetic resonance, methylation analysis, and alpha- and beta-amylase hydrolysis studies that the glucans had glycogen-like structures. These structures were composed of chains of 1-4-alpha-D-glucopyranosyl units with branch points of 4-O- and 6-O-disubstituted D-glucopyranose units. While the backbone structures of the two glucans were similar, the release of maltose by the action of beta-amylase indicated that the 1-4 linked nonreducing side chains of the cell-free enzymically synthesized glucan were longer (approximately seven units) than those present in the cellular glucan (approximately two to three units), a result in agreement with methylation analyses.

Cell-Free System↗