The correlation coefficient in the interpretation of laboratory data.
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Chemistry, Clinical↗
Biomedical subjects
H D Gruemer
Publications and source records attributed to H D Gruemer.
Clinical chemistry education in the United States.
Entrance into a clinical chemistry career in the US can be obtained through a variety of avenues, ranging from very formal to no formal training requirements. A frequent starting point is through a formal medical technology program at the baccalaureate level. Nonphysicians, interested in an advanced career, have also the option to choose their point of entrance through a formal graduate or postdoctoral program. The main source for obtaining a Master of Science or Doctoral degree with a major in the clinical laboratory sciences, is through Departments of Pathology. Physicians desiring to subspecialize in clinical chemistry can obtain some of the training through a residency program in Pathology. Clinical chemistry is an essential component of both the clinical pathology (CP) residency and the combined residencies in anatomic and clinical pathology (AP/CP). In addition, fellowships in clinical chemistry are available for graduates with doctorate degrees in the chemical and biological sciences as well as for physicians with laboratory experience.
Accreditation↗
The correlation coefficient in the interpretation of laboratory data.
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Chemistry, Clinical↗
Serum cortisol and cerebrospinal fluid beta-endorphins in status epilepticus. Their possible relation to prognosis.
OBJECTIVE: To determine if blood cortisol and cerebrospinal fluid beta-endorphin levels correlate with prognosis following status epilepticus. DESIGN: Twenty-seven adult patients with status epilepticus had blood cortisol and cerebrospinal fluid beta-endorphin levels measured within 12 hours after the cessation of clinical seizures. SETTING: Patients with status epilepticus as well as patients with non-status epilepticus seizures came from the Comprehensive Epilepsy Program at the Medical College of Virginia, Richmond. PATIENTS: Twenty-seven patients with status epilepticus. Control patients for the cortisol study were patients who had acute seizures who did not meet the criteria for status epilepticus. The cerebrospinal fluid control subjects were patients without neurologic symptoms undergoing spinal anesthesia. OUTCOME MEASURES: The clinical status of the patients 1 week after status epilepticus as well as the Glascow Outcome Score and the Glascow Coma Score 1 week after status epilepticus. RESULTS: The difference in blood cortisol levels in patients with status epilepticus with poor prognosis was significantly different from both patients with non-status epilepticus seizures (P < .001) and patients with status epilepticus with good prognosis (P < .01). Cerebrospinal fluid beta-endorphin levels were elevated in patients with status epilepticus patients vs control subjects (P < .05), but no significant difference was noted between the patients with status epilepticus with good and poor prognosis. CONCLUSIONS: Serum cortisol levels may provide a useful predictive indicator of prognosis in status epilepticus and cortisol level elevation may play a role in the pathophysiologic condition of status epilepticus.
Adult↗
Identification of a 58-kDa antigen with increased immunoreactivity in the cerebella of multiple sclerosis patients.
An increase in immunoreactivity associated with a 58-kDa antigen was found in a majority of MS cerebellar homogenates examined by Western blot analysis using antisera obtained by selective immunization of rabbits with autopsy cerebella. Two-dimensional immunoblotting demonstrated that the majority of the increased immunoreactivity observed in MS cerebella was associated with the highest apparent pI of three immunoreactive species at 58 kDa. Immuno-crossreaction with rat cerebellar homogenates demonstrated that the 58-kDa antigen was developmentally regulated, showing the greatest immunoreactivity at embryonic day 15. The 58-kDa cerebellar antigen may represent a membrane protein which is re-expressed as part of the onset of MS.
Animals↗
Relationship between CT attenuation changes and post-traumatic CSF-CKBB-activity after severe head injury in man.
In order to evaluate if it is practically possible to assess the volume of contused brain tissue from the CT pictures, a comparison has been carried out between the size of the cerebral contusion(s)--as estimated from the CT scans--and the post-traumatic CSF-CKBB activity, in a series of 29 patients with severe head injury. A clearance curve for the elimination of CKBB from the CSF was constructed. The relation between contusion volume and CSF-CKBB-activity was not statistically significant, while the relationships between contusion volume and outcome, and between CSF-CKBB, as estimated at 6 hours after from the clearance curve, and outcome, were.
Adolescent↗
Use of DNA probes in detecting carriers of Duchenne muscular dystrophy: selected case studies.
Detection of Duchenne muscular dystrophy carriers by genetic analysis is illustrated by four case studies. The technique is most useful in obligate families, in excluding carrier status in isolated cases, and in families in which the affected child demonstrates a molecular deletion. A major limitation of this technique is that the accuracy of carrier status in isolated (i.e., no family history) cases is limited by the probability that the affected child may represent a new mutation. To improve the carrier risk estimate generated by the DNA data, particularly in isolated cases, we suggest that measuring creatine kinase activities in the serum and performing the genetic analysis on the nonaffected males may be helpful.
Alleles↗
An automated procedure for measuring biotinidase activity in serum.
In this automated procedure for quantifying biotinidase activity in human serum, a manual colorimetric method that measures conversion of the enzyme's artificial substrate N-biotinyl p-aminobenzoate was modified for use with a Technicon AutoAnalyzer II. The intra-run replicate precision (CV) was 2.1% and the day-to-day CV was 4.6% for quality-control sera. Results were linearly related to biotinidase activity in serum over the complete range of clinically relevant values, 0.2 to 11.0 U/L. Moreover, results of the automated assay were not significantly different from those of the manual assay. Because the automated procedure is faster and more precise, we recommend it for population-based studies and some screening studies.
Amidohydrolases↗
The regional variability of enzymes in the brain: relevance to CSF enzyme determinations.
The assay of cerebrospinal fluid (CSF) enzymes has been suggested for assessing the extent of damage and patient prognosis in cases of brain injury. A potential difficulty associated with using CSF enzyme levels as predictors of outcome is the possibility that enzyme concentrations may vary substantially from one brain region to another. We have determined the concentrations of seven enzymes in seven brain regions in the rat and cat. Acid phosphatase (ACP), aspartate aminotransferase (AST), isocitrate dehydrogenase (ICDH), lactate dehydrogenase (LD), and malate dehydrogenase (MDH) show little regional variability in the rat and cat while creatine kinase (CK) and glutamate dehydrogenase (GDH) both exhibit considerable regional variability in both animals. Lack of correlation between CSF enzyme levels and prognosis may possibly be explained by the observed regional variability. The enzymes demonstrating more homogeneous concentrations throughout the brain may be better candidates for predicting patient outcome by determination of the CSF enzyme level.
Animals↗
Estimating the soluble enzyme activity in brain tissue.
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Animals↗
Systemic membrane defect and the inhibition of lymphocyte capping in Duchenne muscular dystrophy.
Eight reversible inhibitors were used to study decreases in lymphocyte capping in patients with Duchenne Muscular Dystrophy (DMD) when compared to controls. The inhibitors included hydrocortisone, chlorpromazine, calcium ionophore, Cytochalasin D, propranolol, dibucaine, fluoride and azide. All of these inhibitors disrupt cap formation. Mononuclear leukocytes from DMD patients and controls were isolated from whole blood, incubated with fluorescein-conjugated polyvalent antisera and inhibitor, induced to form caps, and the caps counted using a fluorescent microscope. Cell viabilities and morphology were assessed. After removal of inhibitor, the cells were recounted. All of the inhibitors significantly lowered capping in controls (p less than 0.001), but this effect was seen with only four out of the eight inhibitors in DMD patients. Dibucaine and azide were less inhibitory in patients (p less than 0.005, p greater than 0.05, and p greater than 0.05 respectively) while capping in patients was not inhibited by fluoride and hydrocortisone (p greater than 0.5). The lack of hydrocortisone inhibition suggests that the differences in capping between DMD patients and controls may lie within the membrane itself, rather than its associated components (i.e. cytoskeletal network), and that the defect occurs toward the beginning of the capping sequence.
Cell Membrane↗
Carrier detection in Duchenne muscular dystrophy: a review of current issues and approaches.
The clinical chemistry laboratory has traditionally played a passive role in the application of technology to diagnostic interpretation. Recent developments offer the clinical laboratorian a renewed potential to enter the patient care arena as a consultant. Our lack of understanding of the disease processes in the muscular dystrophies places emphasis on prevention through carrier detection. This review summarizes the clinical progress of the disease, our present understanding of the genetics that control the mode of inheritance of the disease, and the analytical approaches to carrier detection, including their advantages and limitations. Recent advances allow the examination of the genetic material itself instead of concentrating on the phenotypic expression of biochemical abnormalities.
Creatine Kinase↗
Flow characteristics of red cell containing fluids through pores. The effect of filter plugging, a mathematical model.
A mathematical model was developed that describes the effects of filter plugging on flow through 3 micron pore polycarbonate filters as a function of time, pressure, and cell concentration, both under stirring and nonstirring conditions. The mathematical constants for the model were derived from experimental data generated with a filtration apparatus, and were tested by using various concentrations of cells that are able to plug filter pores. A computer simulation program was written to test the model over a wide range of nonfilterable cell concentrations.
Blood Flow Velocity↗
Prognostic significance of ventricular CSF lactic acidosis in severe head injury.
Brain-tissue acidosis inferred by cerebrospinal fluid (CSF) lactic acidosis is considered to play an important role in the clinical course of severe head injury. Ventricular CSF lactate concentration was studied in 19 patients during the first 5 days after severe head injury. All patients were intubated, paralyzed, and artificially ventilated so that PaCO2 was kept at 33.2 +/- 5.0 mm Hg and PaO2 at 122 +/- 18 mm Hg (mean +/- standard deviation). The mean Glasgow Coma Scale score on admission was 5.73 +/- 2.42. The first CSF sample was drawn within 18 hours after head injury. Over the first 4 days postinjury, patients with a poor outcome had significantly higher ventricular CSF lactate levels than did those with moderate disabilities or a good outcome. Patients showing favorable outcome had a significant decrease in ventricular CSF lactate levels 48 hours after injury. This decrease was not observed in patients with a poor outcome. Increased ventricular CSF lactate concentration was also reliably associated with increased intracranial pressure (ICP). Ventricular CSF lactate levels did not correlate with the magnitude of intraventricular bleeding. Arterial and jugular venous blood lactate levels, although high after head injury, were usually lower than the levels in the ventricular CSF and reached a normal range by the 3rd day following head trauma. At that time, the ventricular CSF lactate concentration was still above normal in patients with a poor outcome but had decreased to normal in patients with moderate disabilities or a good outcome. Ventricular CSF pH did not generally correlate with the ventricular CSF lactate concentration in patients under controlled ventilation; however, in a few patients close to death or with ventricular infection, a correlation was noted. Ventricular CSF lactate levels were not related to cerebral blood flow. In this study, profiles of ventricular CSF lactate concentration are defined in relation to the patients' clinical course and outcome. High ventricular CSF lactate concentration is present within 18 hours after severe head injury. Its decrease to normal in the following 48 hours is a reliable sign of clinical improvement; however, ventricular CSF lactate levels that are persistently high or that increase over time indicate the patient's deterioration. Serial assessment of ventricular CSF for acid-base status and metabolites in head-injured patients with a ventricular catheter already placed for ICP monitoring is useful in the evaluation of prognosis and clinical course.
Acidosis, Lactic↗
CSF brain creatine kinase levels and lactic acidosis in severe head injury.
The posttraumatic creatine kinase-BB isoenzyme (CKBB) activity and lactate concentration in ventricular cerebrospinal fluid (CSF) have been studied in 29 patients with severe head injuries. The CKBB activity reaches its maximum a few hours after trauma, and has a monoexponential drop with a half-time of approximately 10 hours. Ventricular CSF lactate concentration continues to rise in patients with a poor outcome, and decreases only slowly and inconsistently in most of the other patients. Thus, increase of lactate in the ventricular CSF is not, like CKBB, a direct one-stage consequence of the trauma but is due to continuous production from a derangement of metabolism caused by the trauma. Since even higher ventricular CSF lactate levels can be survived when not caused by head injury, and since no significant pH changes were related to the ventricular CSF lactic acidosis in these artificially ventilated patients, it is concluded that ventricular CSF lactic acidosis is indicative of a severe, although not necessarily intractable, disturbance of brain function associated with intracellular lactate production and acidosis.
Acidosis, Lactic↗
Prediction of carrier status in Duchenne dystrophy by creatine kinase measurement.
Serum creatine kinase (CK) was measured in 515 healthy white women and 28 obligate carriers for Duchenne muscular dystrophy. There was substantial overlap between the control and carrier populations. To analyze the impact of the degree of overlap, the predictive value of a CK result was determined by (1) using sensitivity and specificity analysis, which assumes dichotomization into a positive or negative result based on a particular cut-off value; and (2) using likelihood ratio analysis, which evaluates an individual result based on the continuum observed for control and carrier populations. There was no clinically important difference whether an observed 57% or a hypothetical 33% overlap between control and carrier results was used. Because of the substantial overlap, the CK test utility is limited to those suspected carriers whose results fall above the healthy population interval. A low CK result does not provide sufficient assurance of noncarrier status.
Adult↗
Blind evaluation of lymphocyte capping in Duchenne muscular dystrophy.
Recently, Pickard et al reported decreased "capping" in lymphocytes from patients with Duchenne type muscular dystrophy (DMD) as well as female carriers of the DMD trait. To resolve subsequent debate about the reproducibility of this finding, we carried out a "blinded" collaborative study designed to eliminate the possibility of observer bias. Blood samples from DMD patients, their mothers, and controls were obtained and coded at Johns Hopkins and transported to the Medical College of Virginia, where lymphocyte capping was tested using FITC-labeled polyvalent anti-human immunoglobulin. Diminished capping in lymphocytes was found in 12 of 13 DMD patients (17 of 18 blood samples) and in 14 of 17 mothers of DMD patients (19 of 23 blood samples), as compared with 8 of 21 control subjects (8 of 22 blood samples). The results in both the patient and the carrier groups differed significantly from those in the control group, confirming previous observations of diminished lymphocyte capping in DMD. The findings provide support for the concept of a systemic defect associated with cell membranes in this disorder. The relatively high incidence of false positive results limits the usefulness of lymphocyte capping as a diagnostic test for carriers under the conditions of this study.
Female↗
Sampling from a skewed population distribution as exemplified by estimation of the creatine kinase upper reference limit.
Creatine kinase (EC 2.7.3.2) was measured in sera from 580 females, ages 1-77 years, and 550 males, ages 1-63 years. The distribution of results for male and female groups shows pronounced skewing toward higher values. The observed distribution of results could not be described by any of six mathematical formulas for skewed distributions, an indication of the unsuitability of such formulas to transform these data for parametric analysis. The range of 97.5 percentile estimates produced by six independent samples of 100, 200, and 400 observations randomly selected from a mathematical model defined by the adult female distribution showed progressive narrowing from the 150-380 U/L interval for the samples of 100 observations to 200-265 U/L for the samples of 400 observations; no further improvement was seen when 800 observations were used. The samples of 100 and 200 observations contained extreme value points that might appear as "outliers" but were shown to be valid members of the population distribution when larger sample sizes were collected.
Adolescent↗