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Biomedical subjects

D A Lacher

Publications and source records attributed to D A Lacher.

At least 19 recordsLinked to original sources
PubMed1997

Immunohistochemical assessment of proliferation markers and altered gene expression in archival specimens of ovarian epithelial tumors.

Recently reported morphologic and molecular genetic evidence suggests that some ovarian carcinomas arise from their benign and low malignant potential (LMP) counterparts. In order to help reach a better understanding of ovarian tumorigenesis, we studied a wide range of gene products involved in cellular growth regulation in archival material obtained from three groups of tumors with graduated malignant potential. Immunohistochemical staining was performed for Ki-67, proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), HER-2/neu-encoded receptor protein, p53 gene product, and multidrug resistance gene product (P-glycoprotein). The expression of EGFR, HER-2/neu-encoded receptor protein, and mutant p53 product was significantly lower in LMP tumors than in carcinomas (p < 0.05). HER-2/neu immunopositivity was more prevalent in adenocarcinomas than in LMP tumors, and the proportion of HER-2/neu-positive adenocarcinomas increased with the progression of the disease. The staining differences between LMP tumors and adenocarcinomas with antibodies against Ki-67, PCNA, and P-glycoprotein were not statistically significant. Immunohistochemical detection of EGFR, HER-2/neu, and p53 in ovarian epithelial tumor is relevant to ovarian tumorigenesis. It could serve as a powerful tool for the pursuit of retrospective studies focused on these important biologic markers.

Adenocarcinoma↗
PubMed1992

The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia.

An abnormal chest roentgenogram is essential for the diagnosis of ventilator-associated pneumonia. The diagnostic accuracy of various roentgenographic signs of pneumonia has not been assessed previously in the portable anteroposterior roentgenograms obtained in ventilated patients. Seven roentgenographic signs (air bronchograms, alveolar infiltrates, silhouette sign, cavities, fissure abutment, atelectasis, and asymmetric infiltrates superimposed on diffuse bilateral infiltrates) were evaluated for their accuracy in predicting pneumonia alone, in combination with other signs, or in combination with clinical parameters. The last roentgenogram prior to autopsy of 69 ventilated patients was interpreted by three reviewers and the above signs were correlated with autopsy evidence of pneumonia. Pneumonia was present in 24 (35 percent) of the 69 autopsies. No roentgenographic sign had a diagnostic efficiency of greater than 68 percent. By stepwise logistic regression, the presence of air bronchograms was the only roentgenographic sign that correlated with pneumonia in the total group, correctly predicting 64 percent of pneumonias. In patients without adult respiratory distress syndrome (ARDS), the presence of air bronchograms or alveolar infiltrates correlated with pneumonia, while in patients with ARDS, no roentgenographic sign and only the clinical parameter of purulent sputum correlated with pneumonia. Only a minority (7/22) of worsening alveolar infiltrates in all groups were due to pneumonia and were often confused with ARDS. Alveolar hemorrhage occurred with a surprising frequency (38 percent of autopsies), including 13/45 (29 percent) patients without pneumonia. Alveolar hemorrhage was associated with 29 percent of multiple air bronchograms and 30 percent of bilateral alveolar infiltrates in patients without pneumonia. We conclude that in intubated patients with diffuse bilateral roentgenographic infiltrates, no roentgenographic sign correlates well with pneumonia. No clinical parameter added to the accuracy of either an alveolar infiltrate or an air bronchogram in patients without diffuse infiltrates. Pulmonary hemorrhage and/or infarction are frequent autopsy findings in intubated patients and may be confused radiologically with pneumonia.

Autopsy↗
PubMed1991

Comparison of nonparametric recursive partitioning to parametric discriminant analyses in laboratory differentiation of hypercalcemia.

Recursive partitioning analysis was compared to logistic, linear and quadratic discriminant analyses in the ability to differentiate hypercalcemic patients with primary hyperparathyroidism from those with malignancy. Stepwise discriminant analysis identified serum albumin as the best single discriminant test. Albumin decision values optimally separating the two hypercalcemic groups were 39.46, 38.54, and 32.25 g/l for the logistic, linear and quadratic discriminant methods, respectively. Recursive partitioning analysis identified carboxy-terminus parathyroid hormone (PTH) as the best discriminant test with an optimal decision value of 8.2 mequiv/l. The discrepancy between the selection of PTH by recursive partitioning analysis and albumin by discriminant techniques was attributed to the nonnormal distribution of PTH. Recursive partitioning analysis using PTH classified 85.4% of the patients correctly. Logistic, linear and quadratic methods, using albumin as the predictor variable, correctly classified 79.6%, 78.6%, and 79.6% of patients, respectively.

Diagnosis, Differential↗
PubMed1990

Relationship between delta checks for selected chemistry tests.

The correlation between delta differences for 20 serum chemistry tests was calculated for 2400 samples from 288 patients. There were 12 pairs of chemistry tests for which correlation coefficients of the delta checks exceeded 0.25; aspartate aminotransferase and alanine aminotransferase had the highest Pearson correlation coefficient, 0.915. The highest negative, indirect, correlation was between the delta checks of bicarbonate and chloride (-0.219). The relationship between delta differences may be used as a quality-control technique to detect analytical errors.

Blood Chemical Analysis↗
PubMed1989

Morphometric evaluation of the renal arterial system of Dahl salt-sensitive and salt-resistant rats on a high salt diet. II. Interlobular arteries and intralobular arterioles.

The progression of small vessel renal vascular disease was studied in inbred Dahl salt-sensitive (SS/Jr) and salt-resistant rats with acute hypertension induced by a high salt diet. Corrected cross-sectional areas of wall (WAC) and lumen were measured by planimetry and histologic staining for fibrin, hyalin deposition, and elastic lamellae was performed. In SS/Jr rats on the high salt diet, the hallmarks of malignant hypertension (fibrinoid necrosis, hyperplastic and necrotizing arteritis) appeared by week 2 and were intensified after 4 weeks on the high salt diet. Renal vascular lesions from SS/Jr rats were characterized by: hyperplasia and/or hypertrophy of medial smooth muscle cells; intimal proliferation; fibrin, basophilic mucoid, and hyalin deposition within the the subendothelial space and media; variable adventitial fibrosis; and accumulation of mononuclear inflammatory cells in the adventitia and media. Interlobular arteries from both rat strains exhibited significantly increased cross-sectional areas over time for all measured parameters. Intralobular arterioles from both rat strains exhibited significantly increased cross-sectional areas over time for all measured parameters except lumen from SS/Jr rats. For SS/Jr rats, increased WAC from both arterial divisions correlated positively with systolic blood pressure, but not body weight. In salt-resistant rats, increased WAC from both arterial divisions correlated positively with body weight, but not systolic blood pressure. We concluded that the rapid increase in WAC from SS/Jr rats could not be attributed solely to the normal growth of the rat. With the development of acute hypertension in the SS/Jr rat, these results demonstrate the potential usefulness of this model to investigate the pathogenesis of similar renal vascular alterations which are observed in man.

Analysis of Variance↗
PubMed1988

Comparison of discriminant analysis procedures in laboratory differentiation of hypercalcemia.

Logistic, linear, and quadratic discriminant analyses were compared in their ability to differentiate hypercalcemic patients with primary hyperparathyroidism from those with malignancy. Linear and quadratic discriminant analyses were performed by use of both untransformed and logarithmically transformed data. Application of principal components analysis with varimax rotation was helpful in revealing the underlying relationships between variables. All discriminant methods identified serum albumin as the best single discriminating test, with the log-quadratic discriminant analysis classifying 81% of patients correctly. The combination of albumin, carboxy-terminal parathyroid hormone, and chloride improved classification accuracy (92% by use of log-quadratic discriminant analysis). Logistic discriminant analysis, using all 20 variables, gave a classification accuracy of 100%. Quadratic discriminant analysis gave better classification than linear discriminant analysis, and both methods performed better when log-transformed data were used. Logistic discriminant analysis followed by discrimination procedures using log-transformed data yielded the highest classification accuracy and reliability of the methods used.

Humans↗
PubMed1988

Rate and delta checks compared for selected chemistry tests.

We compared delta and "rate" check methods for 12 selected chemistry tests. Rate checks were determined by dividing delta checks by inter-specimen interval time. The delta and rate check methods were based on differences and percent change of untransformed and absolute value-transformed values. The distribution of delta differences was not symmetrical for calcium, alkaline phosphatase, aspartate aminotransferase, or phosphorus, which led to different check limits between untransformed and absolute value-transformed methods. The dispersion of rate checks was large. The interval time between two consecutive tests was multimodal, which probably reflected adherence to fixed testing protocols.

Alkaline Phosphatase↗
PubMed1988

Discriminant analysis of laboratory tests in patients admitted to a coronary care unit.

Discriminant analysis of chemistry and hematology laboratory test results was used to classify patients with and without myocardial infarction in a coronary care unit. We studied 64 patients with myocardial infarction and 70 patients without infarction, using logistic regression, linear and quadratic discriminant analyses on untransformed and logarithmically transformed data. Serum aspartate aminotransferase (AST, EC 2.6.1.1), the best single discriminating test, classified 73% of patients correctly. Quadratic discriminant analysis on log-transformed data had a 98.5% classification accuracy when all variables were used in the discriminant function and had the highest classification accuracy and precision. All of the discriminant methods had acceptable cross-validation.

Adult↗
PubMed1987

Predictive value derived from likelihood ratios: a superior technic to interpret quantitative laboratory results.

The predictive value of a quantitative test value calculated from a likelihood ratio is compared with the predictive value of a positive result for computer-simulated laboratory data. A significant loss of information about the magnitude of a quantitative test value occurs when calculating the predictive value of a positive result. This is because of the selection of an arbitrary critical value that classifies the quantitative result as positive or negative. The likelihood ratio (the probability of having disease divided by the probability of not having disease for a given test result) and the prevalence of disease is used to calculate predictive values. Logistic regression is used to predict the likelihood ratio of a test value.

Clinical Laboratory Techniques↗
PubMed1987

Morphometric evaluation of the renal arterial system of Dahl salt-sensitive and salt-resistant rats on a high salt diet. I. Interlobar and arcuate arteries.

Structural changes in intrarenal arteries of inbred Dahl salt-sensitive and salt-resistant rats with acute hypertension were studied morphometrically. After a week on a normal salt diet (1% NaCl), animals were placed on a high salt diet (8% NaCl) for 4 weeks. Systolic blood pressure (BP) and body weights (BW) were recorded, and six salt-sensitive and six salt-resistant animals were sacrificed weekly for a total of five sampling periods. Corrected cross-sectional (C/S) areas of adventitia, media (MAC), intima, wall (WAC), and lumen (LAC) were measured by planimetry. Although significant increases (p less than 0.01) in both BW and systolic BP were observed over time in both strains, salt-sensitive rats became hypertensive (systolic BP greater than 150 mm Hg) by week 2 on a high salt diet, while salt-resistant rats remained normotensive. In interlobar arteries, significant increases over time were observed for the WAC, MAC, and LAC in salt-resistant rats and in the WAC, adventitia, MAC, and LAC for salt-sensitive rats. Significant increases over time were observed for the WAC, adventitia, MAC, and LAC in arcuate arteries from salt-sensitive rats only. Increased C/S areas observed over time in both strains were observed by week 3 on the high salt diet, after the elevated systolic BP. Analysis of covariance indicated that increased C/S areas observed over time in salt-sensitive rats paralleled elevated systolic BP but did not follow an increase in BW. On the other hand, in salt-resistant rats, increased C/S areas observed over time correlated with BW but not systolic BP. The documented rapid development of vascular changes in salt-sensitive rats in conjunction with the development of acute hypertension demonstrates the potential usefulness of this model for investigating the pathogenesis of hypertensive renal vascular alterations.

Animals↗
PubMed1986

Mechanisms of chloroform and carbon tetrachloride toxicity in primary cultured mouse hepatocytes.

Mechanisms of chloroform (CHCl3) and carbon tetrachloride (CCl4) toxicity to primary cultured male B6C3F1 mouse hepatocytes were investigated. The cytotoxicity of both CHCl3 and CCl4 was dose- and duration-dependent. Maximal hepatocyte toxicity, as determined by lactate dehydrogenase leakage into the culture medium, occurred with the highest concentrations of CHCl3 (5 mM) and CCl4 (2.5 mM) used and with the longest duration of treatment (20 hr). CCl4 was approximately 16 times more toxic than CHCl3 to the hepatocytes. The toxicity of these compounds was decreased by adding the mixed function oxidase system (MFOS) inhibitor, SKF-525A (25 microM) to the cultures. The addition of diethyl maleate (0.25 mM), which depletes intracellular glutathione (GSH)-potentiated CHCl3 and CCl4 toxicity. The toxicity of CHCl3 and CCl4 could also be decreased by adding the antioxidants N,N'-diphenyl-p-phenylenediamine (DPPD) (25 microM), alpha-tocopherol acetate (Vitamin E) (0.1 mM), or superoxide dismutase (SOD) (100 U/mL) to the cultures. These results suggest that: in mouse hepatocytes, both CHCl3 and CCl4 are metabolized to toxic components by the MFOS; GSH plays a role in detoxifying those metabolites; free radicals are produced during the metabolism of CHCl3 and CCl4; and free radicals may be important mediators of the toxicity of these two halomethanes.

Animals↗
PubMed1986

How computers are used in pathology education.

How are computers being used to teach pathology? Of 129 major medical teaching institutions surveyed, 63 institutions responded and 37 were using computers in pathology education. Applications include examination, instruction and consultation, case simulation, and course evaluation.

Computer-Assisted Instruction↗
PubMed1986

Determination of amylase activity in serum by using a wheat germ inhibitor with the Du Pont aca.

A rapid procedure for determining salivary- and pancreatic-type amylase (EC 3.2.1.1) in serum by incorporating a wheat germ inhibitor (from Triticum aestivum) was developed for the Du Pont aca IV analyzer. Under optimal assay conditions, activities of salivary and pancreatic amylase were inhibited by 93% and 19%, respectively. The 95% central reference interval for the percentage of inhibition of serum amylase was 38-84%. Patients with acute pancreatitis showed less than 26% inhibition of amylase after addition of the wheat germ extract, reflecting the prevalence of pancreatic-type amylase in this disorder.

Acute Disease↗