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Biomedical subjects

J Michaelis

Publications and source records attributed to J Michaelis.

At least 19 recordsLinked to original sources
PubMed1992

Different effects of hypochlorous acid on human neutrophil metalloproteinases: activation of collagenase and inactivation of collagenase and gelatinase.

Human neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA) produce the reactive oxidant hypochlorous acid (HOCl) and release the matrix metalloproteinases collagenase and gelatinase from secretory granules. We have investigated the stoichiometry of activation and inactivation of the two metalloproteinases with HOCl. HOCl activated purified neutrophil procollagenase at ratios between 10 and 40 mol of HOCl/mol enzyme, but caused inactivation at higher ratios. Maximum activation was about the same as that achieved by p-aminophenyl-mercuric acetate. However, less than a third of the total collagenase released from PMA-stimulated neutrophils was activated by coreleased HOCl and most of the activity was destroyed after 1 h of stimulation. These results indicate that the HOCl/enzyme ratio must fall within a narrow range for activation to occur. In contrast to collagenase, purified progelatinase underwent negligible activation (2.5 +/- 1.2%) at HOCl/enzyme molar ratios less than 30 and was destroyed at higher ratios. Likewise no active gelatinase could be detected in supernatant from PMA-stimulated cells and almost all of the proenzyme was destroyed by HOCl after 60 min stimulation. Our results illustrate that only collagenase can be activated by HOCl in vitro and that gelatinase is much more sensitive to inactivation. Since a precise HOCl/enzyme ratio is required for collagenase activation it is doubtful whether effective enzyme regulation by HOCl could occur in vivo where various HOCl scavengers are present.

Electrophoresis, Polyacrylamide Gel↗
PubMed1992

Incidence of childhood malignancies in the vicinity of west German nuclear power plants.

The incidence of childhood malignancies in 20 areas surrounding major nuclear installations is compared with the incidence in matched control regions. The study is based on the registry of childhood malignancies in the Federal Republic of Germany and includes 1,610 cases which were diagnosed before 15 years of age from 1980 to 1990. The relative risk (RR) was 0.97 for all malignancies and 1.06 for acute leukemia in all regions within a 15 km radius of an installation. Increased RR was observed in subgroups for acute leukemia before five years of age and for lymphomas, especially in regions close to installations (less than 5 km) which started operation before 1970. Most of this increase was attributable to an unexpectedly low incidence in the control regions which could not be explained by analyzing possible confounding factors. Using the same control regions, a comparable and even more pronounced increase of RRs was observed in regions where nuclear power plants have been projected.

Adolescent↗
PubMed1992

Risk assessment of future myocardial infarction from automated serial ECG analysis.

From 1980 to 1990 a cohort of 7,542 employees took part in the MARISK study. This study was designed in order to explore the utility of computerized electrocardiographic (ECG) measurements for predicting future myocardial infarction. After an initial period of annual examinations, follow-up information was collected by mailed questionnaires and obtained from 89.3% of all study participants with a median follow-up time of more than 7 years. Eighty-three participants suffered from myocardial infarction during the course of the study. Multivariate logistic regression analysis revealed that automated ECG measurements contribute significant additional information to risk estimates obtained from classical risk factors. Serial ECG analysis yields stronger risk indicators than single measurements. Results are represented via receiver operating characteristic (ROC) curves and regression coefficients, which can be used in independent applications. The results of this study indicate that it is useful to include automated serial ECG analysis in cardiovascular screening programs. It still has to be evaluated whether successful preventive measures may be based on such screening programs.

Cohort Studies↗
PubMed1992

The 1989 Loma Prieta earthquake: impact on hospital patient care.

STUDY OBJECTIVE: To provide an overview of the Loma Prieta earthquake regarding patient care in affected hospitals. DESIGN: A retrospective review of medical records using International Classification of Disease, ninth revision (ICD-9) codes and a personal interview questionnaire. SETTING: Fifty-one hospitals in the six-county area most affected by the earthquake. TYPE OF PARTICIPANTS: Patients seeking care in emergency departments of study hospitals and supervising emergency physicians and ED nurses at the time of the earthquake. MEASUREMENTS: ED census data, complaint and diagnosis, disposition, and operative procedures for patients seen during the study period. MAIN RESULTS: Affected hospitals experienced a 15% increase in ED census during the study period. Minor trauma was the most common patient complaint. Open wound (870-897), contusion (920-924), and fracture (800-829) were the most common ICD-9 diagnostic categories. The percentage of patients presenting to EDs during the study period who were hospitalized increased slightly compared with baseline. Seventy-five percent of operative procedures were earthquake related; 63.7% of these were for fracture reduction. Physicians and nurses had somewhat conflicting opinions on adequacy of ED staffing. A small number of emergency physicians had difficulty in obtaining diagnostic tests on the night of the earthquake. Physicians noted no differences in diagnosis or treatment resulting from the earthquake. CONCLUSION: The Loma Prieta earthquake resulted in minimal negative impact on patient care in hospitals in the study area. The use of the ICD-9 classification deserves further consideration and study to improve the predictive value of disaster illness and injury reporting. The event has provided the stimulus for Bay Area hospitals to further improve plans for patient care during a disaster.

California↗
PubMed1992

Latent collagenase and gelatinase from human neutrophils and their activation.

Procollagenase M(r) 85,000 (SDS-PAGE) was purified from buffy coat to homogeneity and represents a stable single polypeptide chain forming the entire proenzyme. The procollagenase can be activated by various proteinases, e.g. trypsin, chymotrypsin, cathepsin G, kallikrein and stromelysin and by different mercurial compounds. Proteolytic conversion of the latent enzyme to the active form by chymotrypsin is accompanied by a molecular weight reduction to an apparent M(r) 64,000. This active enzyme lacks the first 79 N-terminal residues. Activation by trypsin leads to a latent intermediate of apparent M(r) 70,000, lacking 48 N-terminal residues. The active enzyme is therefore generated upon prolonged incubation with trypsin by further cleavage of 22 N-terminal residues. Another latent intermediate form with apparent M(r) 69,000 is generated from the proenzyme upon incubation with leukocyte elastase by N-terminal cleavage of 53 or 64 residues, respectively. However, latent collagenase cannot be activated by plasmin. Activation by different mercurial compounds finally results in the formation of active collagenase with apparent M(r) 64,000. In contrast to the proenzyme, active collagenase can autolyse to give active M(r) 57,000 and 45,000 intermediates and two M(r) 28,000 fragments. Purification of latent leukocyte gelatinase yields three final products with apparent M(r) 98,000, 125,000 and 220,000 (SDS-PAGE; non reduced). Upon reduction, only the M(r) 98,000 form can be detected. The latent gelatinase can be activated in a similar manner as collagenase. Proteolytic activation by trypsin leads after N-terminal cleavage to an active gelatinase with sequence homology to leukocyte collagenase.

Amino Acid Sequence↗
PubMed1992

Recommendations of the German Association for Medical Informatics, Biometry and Epidemiology for education and training in medical informatics.

In the fields of health care and medicine there is an immense demand for a systematic application of methods of information processing and for the use of computers. Obviously, to that end well-trained scientists and qualified personnel must be available. With the present recommendations on education and training in medical informatics the German Association for Medical Informatics, Biometry and Epidemiology (GMDS) proposes structure and contents of medical informatics curricula and courses. The recommendations describe a 2-dimensional educational framework with different education levels in one dimension and various types of educational needs and orientation in the other one. The recommendations comprise at the university level education as well specialized curricula covering the total spectrum of medical informatics as well as informatics curricula with medical informatics as integrated applied subject or subsidiary subject, respectively. Besides these informatics-oriented approaches medical-oriented programs of education in medical informatics are recommended, e.g., post-graduate education in medical informatics for physicians based on foundations in medical informatics as part of their initial training in medicine. At the level of polytechnical schools curricula of medical documentation and informatics and at the level of professional schools training in medical documentation are recommended. This report is a translation of its German original. Although considered by the GMDS as recommendations for the Federal Republic of Germany, the text may also contribute to the development of an international, especially European framework of training in medical informatics.

Germany↗
PubMed1991

Hydrochlorothiazide and verapamil in the treatment of hypertension. The Verapamil Versus Diuretic (VERDI) Trial Research Group.

The efficacy and tolerability of hydrochlorothiazide, sustained-release verapamil, and their combination was compared in patients with mild to moderate hypertension. The design was a multicenter, randomized, double-blind clinical trial with a single-blind placebo baseline period of 2 weeks. Three hundred sixty-nine patients with a diastolic blood pressure of 95-120 mm Hg were included. Treatment consisted of 12.5 mg of hydrochlorothiazide once daily, then 25 mg once daily, and finally 25 mg twice daily; the other group received verapamil at a dose of 120 mg once daily, then 240 mg once daily, and finally 240 mg twice daily. Patients not achieving target blood pressure (less than 90 mm Hg diastolic) were given the combination of hydrochlorothiazide and verapamil, that is, 25 and 240 mg once daily and twice daily. During all time points during the study patients receiving verapamil achieved target blood pressure more often than patients receiving hydrochlorothiazide (after 8 weeks, 57.7 and 42.7%; after 24 weeks, 46.8 and 26.4%; and after 48 weeks, 44.8 and 24.7%, respectively). Adding verapamil to hydrochlorothiazide was more effective in lowering blood pressure than adding hydrochlorothiazide to verapamil. The number of treatment withdrawals was essentially the same with the two drugs. Therefore, in the doses currently used in antihypertensive treatment, verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension.

Adult↗
PubMed1991

Elements of significance testing with equivalence problems.

The paper outlines an approach to the general methodological problem of equivalence assessment which is based on the classical theory of testing statistical hypotheses. Within this frame of reference it is natural to search for decision rules satisfying the same criteria of optimality which are customarily applied in deriving solutions to one- and two-sided testing problems. For three standard situations very frequently encountered in medical applications of statistics, a concise account of such an optimal test for equivalence is presented. It is pointed out that tests based on the well-known principle of confidence interval inclusion are valid in the sense of guaranteeing the prespecified level of significance, but tend to have an unnecessarily low efficiency.

Confidence Intervals↗
PubMed1990

Human neutrophil collagenase cleaves alpha 1-antitrypsin.

Inactivation of the plasma serine-proteinase inhibitor alpha 1-antitrypsin (alpha 1-AT) by neutrophil metalloproteinases has been reported [Vissers, George, Bathurst, Brennan & Winterbourn (1987) Fed. Proc. Fed. Am. Soc. Exp. Biol. 46, 1390a; (1988) J. Clin. Invest. 82, 706-711; Desrochers & Weiss (1988) J. Clin. Invest. 81, 1646-1650]. To identify the enzyme responsible, supernatant from neutrophils stimulated with phorbol 12-myristate 13-acetate was subjected to preparative SDS/PAGE, both with and without activation of latent metalloproteinases with HgCl2. The lanes were subsequently sliced into pieces, the slices incubated with equimolar amounts of type I collagen and alpha 1-AT in the presence of HgCl2, and the reaction products separated by SDS/PAGE. With the latent supernatant, the characteristic collagen-cleavage products and cleaved alpha 1-AT were present in the same slices, corresponding to an Mr of 80,000-85,000. On treatment with HgCl2 both degradative activities underwent the same molecular-mass shift to a position corresponding to Mr 60,000-65,000. Western blots of neutrophil supernatants, using a polyclonal antibody to purified collagenase, showed Mr values of 83,000 for the latent enzyme and 63,000 for the HgCl2-activated enzyme. Neutrophil collagenase was purified to homogeneity and shown also to exist in a second latent form with Mr 70,000. When activated to the Mr-63,000 form by HgCl2 and incubated with equimolar amounts of collagen and alpha 1-AT, collagenase cleaved alpha 1-AT at almost twice the rate at which collagen was cleaved. alpha 1-AT cleavage was inhibited by 1,10-phenanthroline and by high concentrations of collagen. That the purified collagenase did not contain a contaminant proteinase such as stromelysin was indicated by inability of the preparation to cleave casein. Taken together these results lead us to conclude that neutrophil collagenase is capable of degrading alpha 1-AT. Neutrophil gelatinase also cleaved alpha 1-AT, but cleavage was slow when compared with its activity against gelatin.

Caseins↗
PubMed1990

[The importance of preoperative chemotherapy and radiotherapy in 373 children with Wilms' tumor].

Between 1980 and 1988, in a prospective study of 373 children with Wilms' tumour throughout the Federal Republic of Germany, the results of various pre- and postoperative treatment schedules were analysed. There were 184 boys and 189 girls, mean age 3 11/12 (0-27) years. One third each was in group I, II or III-V, respectively. In 52% of cases the tumour volume, measured by ultrasound, was more than 400 ml. 218 of the children were called protocol patients, the remaining 155 served as observation patients, because the latter had histological variants or there had been marked treatment deviations. The stage-adapted treatment always included operation, in 30% of children after pre-operative chemo- or radiotherapy. Radiotherapy was given in selected patients in stage II and always to those in stages III, IV or V. Chemotherapy consisted of Actinomycin D and vincristine, adriamycin was added for stages III-V and cyclophosphamide or ifosfamide for histologically highly malignant variants. Of the 218 protocol patients 196 (90%) were alive without recurrence, after a mean observation time of more than 7 years. Radiotherapy was given to only 105 of the 218 protocol patients. The prognosis of the 155 observation patients differed according to the histology: those with clear-cell type had a better prognosis than previously reported. Among the total group of 373 patients 305 (81.8%) have remained without recurrence after more than 6 years.

Adolescent↗
PubMed1990

The activation of human neutrophil gelatinase.

To study the mechanisms of activation of human neutrophil gelatinase, the enzyme has been purified using a combination of chromatography on a DEAE-Sephacel and a gelatin-peptide-Sepharose column. On reducing SDS-polyacrylamide-gel electrophoresis the purified gelatinase ran as a single band of about 94,000 Da, and had a specific activity of 5624.4 units/mg of enzyme protein. When latent gelatinase was treated with trypsin, cathepsin G, neutrophil elastase, HgCl2 or urea, its activity was enhanced and the enzyme was processed and converted into species of the lower molecular mass. Upon activation, the protein band of 94,000 Da of reduced latent gelatinase underwent a decrease of about 6,000-12,000 Da. Formation of the species of lower molecular mass during urea activation could be blocked by the addition of EDTA.

Chromatography, Affinity↗
PubMed1990

Use of information from clinical trials for an integrated cancer registry.

The registry of childhood malignancies in the F.R.G. is a combination of a population-based and hospital-based cancer registry. A large amount of the collected data originates from multicenter clinical trials which are integrated into the documentation system of the cancer registry. The paper describes the information flow and the system of data storage which consists of a central database on a departmental system at the registry and of several coordinated peripheral databases on microcomputers at the trial centers. Practical experience shows an increased availability and validity of the data in the registry since the implementation of the system. Aspects of data integrity and security are discussed. Although the system was designed according to specific demands of the registry, it may serve as a model for similar tasks of cooperative documentation and information exchange.

Child↗
PubMed1990

Reference standards for software evaluation.

The field of automated ECG analysis was one of the earliest topics in Medical Informatics and may be regarded as a model both for computer-assisted medical diagnosis and for evaluating medical diagnostic programs. The CSE project has set reference standards of two kinds: In a broad sense, a standard how to perform a comprehensive evaluation study, in a narrow sense, standards as specific references for evaluating computer ECG programs. The evaluation methodology used within the CSE project is described as a basis for presentation of results which are published elsewhere in this issue.

Diagnosis, Computer-Assisted↗
PubMed1990

Evaluation of ECG interpretation results obtained by computer and cardiologists.

In an international project investigators from 25 institutes are trying to establish a common reference library and evaluation methods for testing the diagnostic performance of various ECG computer programs and of cardiologists, based on ECG-independent clinical information. A first set of 500 validated ECGs was collected and analyzed by fifteen different computer programs and nine cardiologists, seven of who analysed the ECG and five the VCG. A coding scheme was used to map individual diagnostic statements onto a common set. Combined program and referee results were obtained by weighted averaging. Preliminary results indicate that the classification accuracy of several programs can still be improved. However, it was also apparent that the results of the best 12-lead ECG computer programs proved to be almost as accurate as the best of seven cardiologists in classifying seven main disease categories, i.e., normal, left, right and biventricular hypertrophy, anterior, inferior and combined myocardial infarction. Evaluation of rhythm statements and conduction disturbances was not included in the study. The data collection is still being pursued in order to reach over 1,000 cases. In this way a common diagnostic database is being established for comparative testing of diagnostic computer programs. This should lead to consumer protection and improve the accuracy and reliability of computerized electrocardiography.

Cardiovascular Diseases↗
PubMed1989

Verapamil versus hydrochlorothiazide in the treatment of hypertension: results of long term double blind comparative trial. Verapamil versus Diuretic (VERDI) Trial Research Group.

OBJECTIVE: To compare the efficacy and tolerability of hydrochlorothiazide, sustained release verapamil, and their combination in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial of 48 weeks' duration with a double blind comparison of hydrochlorothiazide and verapamil followed by an open trial of combined treatment for patients not achieving the target diastolic blood pressure (less than 90 mm Hg) during treatment with a single drug. SETTING: Outpatient departments in 10 clinics and 10 private practices of general practitioners or internists. PATIENTS: 369 Hypertensive patients with a diastolic blood pressure of 95-120 mm Hg during a placebo run in period of two weeks. INTERVENTIONS: Initial treatment consisted of 12.5 mg hydrochlorothiazide (n = 187) or 120 mg sustained release verapamil (n = 182) once daily (regimen I). If the target diastolic blood pressure of less than 90 mm Hg was not achieved within four weeks doses were increased to 25 mg hydrochlorothiazide or 240 mg verapamil once (regimen II) and twice daily (regimen III). Patients not achieving target blood pressure were given the combination of hydrochlorothiazide and verapamil--that is, 25 and 240 mg once (regimen IV) and twice daily (regimen V). MAIN OUTCOME MEASURE: Blood pressure determined with a device permitting automatic repeated measurements with printouts. RESULTS: After eight weeks of treatment with a single drug 76 out of 178 (43%) and 101 out of 175 (58%) patients achieved the target blood pressure with hydrochlorothiazide and verapamil, respectively. During follow up until 48 weeks patients treated with verapamil reached the target blood pressure more often and at lower doses and were less likely to switch to combination treatment than patients randomised to hydrochlorothiazide treatment. Adding verapamil to hydrochlorothiazide was more effective than the addition of hydrochlorothiazide to verapamil. At the end of the study 42 out of 169 (25%) and 73 out of 163 (45%) patients initially randomised to hydrochlorothiazide and verapamil, respectively, were at target blood pressure without combination treatment. After adding verapamil to hydrochlorothiazide or hydrochlorothiazide to verapamil an additional 58 (34%) and 29 (18%) patients reached the target blood pressure, respectively. Altogether 92 out of 332 (28%) patients failed to achieve target blood pressure with regimen V. There were four, 10, seven, and seven withdrawals due to possible adverse effects to treatment with hydrochlorothiazide, verapamil, combining verapamil with hydrochlorothiazide, and combining hydrochlorothiazide with verapamil, respectively. CONCLUSIONS: In doses currently used in antihypertensive treatment verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension, whereas withdrawal rates caused by side effects possibly related to treatment were similar.

Adult↗