Do normal leucocyte count and C-reactive protein on admission to hospital exclude a life-threatening attack of acute pancreatitis?

BACKGROUND AND AIMS: The early severity assessment of an attack of acute pancreatitis is clinically of utmost importance. The aim of the present work was to study the role of leucocyte count and C-reactive protein (CRP) measurements on admission to hospital in assessing the severity of an attack of acute pancreatitis. In particular, patients with a life-threatening attack of acute pancreatitis but a normal leucocyte count and CRP level were sought. MATERIAL AND METHODS: A total of 1050 attacks of acute pancreatitis were treated at Turku University Central Hospital during the years 1995-1999. Leucocyte count and C-reactive protein (CRP) value were determined on admission to hospital. There were 58 life-threatening attacks of acute pancreatitis (group A). Fifty-eight consecutive mild attacks served as controls (group B). The number of patients with both values normal, only leucocyte count raised, only CRP level raised and both values raised were calculated in the groups A and B. RESULTS: Both leucocyte count and CRP level were significantly (P < 0.001 in both comparisons) higher on admission to hospital in patients with a life-threatening disease (group A) than in those with a mild disease (group B). Group A contained no patients with both values in the normal range. In group B, one fifth of the patients had both values normal. CONCLUSION: It is very unlikely that acute pancreatitis proves to be a life-threatening one when both the leucocyte count and CRP are normal on admission to hospital. In the present 1050 acute pancreatitis there were no patients with life-threatening disease but normal laboratory values on admission.

Frequency and clinical outcome of potentially harmful drug metabolic interactions in patients hospitalized on internal and pulmonary medicine wards: focus on warfarin and cisapride.

Drug metabolic interactions present potential risks in patient care, but their frequency and relative importance as a clinical problem remains unclear. To assess the frequency and clinical outcome of potentially harmful drug metabolic interactions in hospitalized patients, the authors performed a survey of the medication data of patients treated on internal and pulmonary medicine wards in a university hospital. The database was searched for concomitantly administered drug pairs that would, according to Hansten and Horn's drug interaction database, carry a high risk for a clinically harmful metabolic drug interaction. Coadministrations involving warfarin or cisapride were subjected to further analysis regarding clinical outcome. A total of 142 patients were exposed to 150 interactions with potentially harmful clinical outcome, resulting in a frequency of 0.9% (95% CI 0.7% to 1.0%). Inhibition of warfarin metabolism by metronidazole produced significant overanticoagulation as evidenced by elevated international normalized ratio values, whereas inducers (rifampicin and phenobarbital) of warfarin metabolism significantly reduced the efficacy of warfarin. One case of minor bleeding and one case of clavicular vein thrombosis were detected as possible consequences of disturbed anticoagulation. The coadministration of cisapride and erythromycin significantly prolonged the corrected QT (QTc) interval and was associated with clinical symptoms of cardiac arrhythmias. Coadministration of cisapride with fluconazole or miconazole was not associated with prolongation of the QTc interval or cardiac sequelae. Evaluations of patient materials are needed to assess the clinical relevance of metabolic drug interactions.

Reminders of drug effects on laboratory test results.

Drug effects on laboratory test results are difficult to take into account without an online decision support system. In this study, drug effects on hormone test results were coded using a drug-laboratory effect (DLE) code. The criteria that trigger the reminders were defined. To issue reminders, it was necessary to write a computer program linking the DLE knowledge base with databases containing individual patient medication and laboratory test results. During the first 10 months, 11% of the results from hormone samples were accompanied by one or more DLE reminders. The most common drugs to trigger reminders were glucocorticoids, furosemide, and metoclopramide. Physicians facing the reminders completed a questionnaire on the usefulness of the reminders. All respondents considered them useful. In addition, DLE reminders had caused 74% of respondents to refrain from additional, usually performed examinations. In conclusion, drug effects on laboratory tests should always be considered when interpreting laboratory results. An online reminder system is useful in displaying potential drug effects alongside test results.

A fertile-aged woman with right lower abdominal pain but unelevated leukocyte count and C-reactive protein. Acute appendicitis is very unlikely.

BACKGROUND AND AIMS: An uninflamed appendix at appendectomy represents a misdiagnosis. In fertile-aged women, the diagnostic accuracy in acute appendicitis is usually lower than 60%. We studied the role of preoperative leukocyte count and C-reactive protein (CRP) measurements in the diagnosis of acute appendicitis in fertile-aged women with a clinical suspicion of acute appendicitis. In particular, what is the clinical value of unelevated leukocyte count and CRP in excluding acute appendicitis in these patients? METHODS: We calculated the mean leukocyte count and CRP values in (1) 100 consecutive fertile-aged women operated on for a clinical suspicion of acute appendicitis but with an uninflamed appendix found at appendectomy, and (2) 100 consecutive fertile-aged women operated on for a clinical suspicion of acute appendicitis and acute appendicitis found at appendectomy. The percentages of patients with (1) both values unelevated, (2) only leukocyte count elevated, (3) only CRP value elevated, or (4) both values elevated were calculated within the groups A (uninflamed appendix) and B (acute appendicitis). RESULTS: The mean leukocyte value was significantly (P<0.001) higher in patients with acute appendicitis (13.7x10(9)/l) than in those with an uninflamed appendix (10.6x10(9)/l). Similarly, the mean CRP value was significantly (P<0.05) higher in patients with acute appendicitis (42 mg/l) than in those with an uninflamed appendix(29 mg/l). Taken together, 24 patients were operated on for a clinical suspicion of acute appendicitis, although preoperative leukocyte count and CRP values were unelevated. An uninflamed appendix was found in all these patients at appendectomy. CONCLUSION: Although clinical symptoms and signs indicated acute appendicitis, unelevated leukocyte count and CRP values excluded it, with a 100% predictive value in the current study of fertile-aged women. In our patients, 24% (24 of 100) of unnecessary appendectomies could have been avoided by trusting in this finding.

Spectral analysis of heart rate variability as a quantitative measure of parasympatholytic effect--integrated pharmacokinetics and pharmacodynamics of three anticholinergic drugs.

The time course and concentration-effect relationship of parasympatholytic effects of three anticholinergic drugs were investigated using spectral analysis of heart rate (HR) variability. Single intravenous (i.v.) doses of atropine (10 microg/kg), glycopyrrolate (5 microg/kg), scopolamine (5 microg/kg), and placebo were given to eight healthy volunteers in a double-blind, randomized cross-over study. Electrocardiogram (ECG) was recorded at baseline and 2.5, 5, 10, 20, and 30 minutes, and 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration, while the subjects breathed at a fixed 0.25 Hz frequency. The powers of two frequency bands (low frequency [LF] = 0.07-0.15 Hz and high frequency [HF] = 0.15-0.40 Hz) were calculated using stationary time series of R-R intervals (RRI) free from ectopic beats. To perform pharmacokinetic-pharmacodynamic (PK-PD) modeling, venous plasma drug concentrations were measured. Atropine and glycopyrrolate, and, to a lesser extent, scopolamine induced decreases in HF power and increases in LF/HF ratio of HR variability, indicating parasympatholytic activity and corresponding changes in sympathovagal balance. Maximal average decreases in HF power were 99%, 94%, and 82%, respectively, but in two scopolamine subjects, a parasympathomimetic effect was dominant. Interindividual variability was least for the Hayano index of HF power (square root (RRI HF-power)/RRI*100), and profound and consistent decreases were seen after atropine and glycopyrrolate. Pharmacokinetics were best fitted to a two-compartment open model, and effect compartment link modeling using the Hayano index was performed with the atropine and glycopyrrolate data. The best description of the PK-PD relationship for both drugs was achieved using the sigmoidal Emax model. Mean (+/-SD) EC50, sigmoidicity factor (gamma), and equilibration rate constant (k(e0)) estimates were 1.35 (+/-0.27) ng/mL, 6.07 (+/-1.98) and 11.0 (+/-5.28) l/h for atropine and 1.35 (+/-0.49) ng/mL, 4.34 (+/-1.55) and 2.26 (+/-0.81) l/h for glycopyrrolate. Spectral analysis of HR variability appears to be a powerful tool in monitoring parasympatholytic drug activity. A sigmoidal Emax model with an extremely steep concentration-response relationship was revealed for atropine and glycopyrrolate. The effects of scopolamine were more incongruous.

Leucocyte count and C-reactive protein in the diagnosis of acute appendicitis.

BACKGROUND: The aim of the present work was to study the preoperative leucocyte counts and C-reactive protein (CRP) values in three groups of patients operated on for a clinical suspicion of acute appendicitis with different findings at appendicectomy: an uninflamed appendix, uncomplicated acute appendicitis or complicated acute appendicitis. In particular, patients with acute appendicitis but a normal leucocyte count and CRP level were sought. METHODS: In this retrospective study, the mean preoperative leucocyte count and CRP value in 100 consecutive patients with an uninflamed appendix (group A), in 100 consecutive patients with uncomplicated acute appendicitis (group B) and in 100 consecutive patients with complicated acute appendicitis (group C) were calculated. The numbers of patients with (1) both values normal, (2) only leucocyte count raised, (3) only CRP level raised and (4) both values raised were calculated in each of the three groups. RESULTS: The increase in leucocyte count was an early marker of appendiceal inflammation, whereas the CRP value increased markedly only after appendiceal perforation or abscess formation. Group A (uninflamed appendix) contained 24 patients in whom both values were normal. Neither group B (uncomplicated acute appendicitis) nor group C (complicated acute appendicitis) contained any patient with both values in the normal range. CONCLUSION: Acute appendicitis is very unlikely when both the leucocyte count and CRP value are normal.

Preanalytical and analytical factors affecting laboratory results.

The results of laboratory tests have a substantial role in the diagnostics of diseases. However, laboratory results do not always correspond with the patient's clinical status. They may be unexpected and surprising. On the other hand, an abnormal laboratory result may be accepted as such and interpreted as a sign of a disease. However, an abnormal result may result from several factors other than disease. Conventionally, these interfering factors have been divided into preanalytical and analytical factors and furthermore into factors acting in vivo and in vitro. The list of these factors is long and laborious to bear in mind. In this review we focus on the factors which, in practice, most often affect laboratory results in healthy individuals and which explain an unexpected result.

Response of serum total renin to ramipril and metoprolol in hypertensive patients.

Renin-angiotensin system has long been thought to be a classic endocrine negative feedback system in the pathophysiology of hypertension. Furthermore, angiotensin II formation was believed to be regulated by renin secreted from the kidneys. In contrast to these considerations is the identification of local angiotensin II production in other tissues than pulmonary vasculature. Prorenin, the molecular precursor of renin, has been assumed to be involved in local angiotensin II production because of its renin-like activity. Prorenin has also been found to be secreted from extrarenal sources, although a major part of it is derived from the kidneys. Increased concentration of total renin in serum has been proposed to be useful in identifying patients with active proliferative retinopathy in insulin-dependent diabetic patients. Renin-angiotensin system is strongly affected by angiotensin-converting enzyme (ACE) inhibitors and therefore the interfering effect of ACE inhibitor medication on total renin concentration should be known in order to interpret serum total renin concentrations. Nine hypertensive outpatients, all men, treated at the department of internal medicine in Turku University Central Hospital, received randomly 5 mg of ramipril or 95 mg of metoprolol once a day for 4 weeks. Ramipril significantly increased the mean value of total renin (191.9 ng/l vs 312.0 ng/l, p < 0.01), but the metoprolol-induced increase in the concentration of serum total renin was insignificant. We conclude that the negative feedback mechanism in regulating renin and prorenin secretion was inhibited by ACE inhibitor ramipril but beta 1-selective adrenoceptor antagonist metoprolol did not significantly change total renin concentration in serum.

Effects of ramipril on the hormone concentrations in serum of hypertensive patients.

The effects of the angiotensin-converting enzyme inhibitor ramipril on thirteen endocrinological tests were evaluated. These tests comprised serum follitropin, lutropin, prolactin, thyrotropin, free thyroxine, total thyroxine, free triiodothyronine, parathyrin, cortisol, testosterone, sex hormone binding globulin, androstenedione and dehydroepiandrosterone sulphate. Eleven hypertensive outpatients, 9 men and 2 women, treated at the department of internal medicine in Turku University Central Hospital, received 5 mg of ramipril once a day for the study period of four weeks. The above mentioned endocrinological tests were performed before and at the end of the ramipril treatment. Ramipril decreased the value of free thyroxine statistically significantly, p = 0.011, from the mean value of 17.1 pmol/l to the mean value of 16.0 pmol/l when measured with Amerlex-MAB* free thyroxine kit. The mean within-subject difference was -1.10 pmol/l with a 95% confidence interval of -1.87 - -0.33 pmol/l. With the AutoDELFIA free thyroxine kit and with the reference method dialysis+RIA no effect was detected. Other endocrinological tests examined were not affected by ramipril. Since the decreasing effect of ramipril on free thyroxine was detected only with Amerlex-MAB* but neither with AutoDELFIA nor with dialysis+RIA, the effect was concluded to be analytical. The underlying mechanism and the component ultimately interfering with the analysis is unknown.

A medication database--a tool for detecting drug interactions in hospital.

OBJECTIVE: Drug interactions may lead to life-threatening injuries. More often, however, they lead to slow recovery, induce slight symptoms or result only in potential injury. Therefore, clinicians are not always aware of using potentially interacting drug combinations. An on-line alarming system of potential drug interactions was developed in Turku University Central Hospital. In the present study, we utilised the system to find out the incidence and nature of potential drug interactions occurring in a representative hospital patient population. METHODS: Computerised anatomical therapeutic chemical (ATC)-coded patient medication data of 2547 patients, treated in two internal medicine wards, were combined with an ATC-coded rule base of drug interactions. All potential drug interactions in the study population were searched for. RESULTS: A total of 326 potentially serious drug interactions were detected in the study population. The number of patients in this group was 173, i.e. 6.8% of all patients had one or several drug combinations which might have led to serious clinical consequences. Concomitant use of calcium and fluoroquinolones (decreased absorption) was the most common mistake (66 prescriptions). CONCLUSIONS: Potentially inappropriate drug combinations seem to occur frequently. Structured and coded medication data can be utilised efficiently to detect potential drug interactions in hospital. Computerised online monitoring and automatic alarming of potentially hazardous drug combinations might help clinicians to prescribe more safely, but further development of the system is needed to avoid unnecessary alarms.

Computerized monitoring of potentially interfering medication in thyroid function diagnostics.

OBJECTIVE: Many drugs are known to affect the results of laboratory tests. This may cause problems in the interpretation of clinical laboratory data and lead to wrong diagnoses, unnecessary further tests and additional costs. A computerized monitoring system of potential drug effects on laboratory tests was developed in Turku University Central Hospital. In the present study the incidence and nature of potentially interfering drug effects in thyroid function diagnostics was examined in order to ease the clinical implementation of the system. METHODS: Computerized medication data of 754 hospital in-patients whose thyroid function was tested were combined with a knowledge base of drug effects on laboratory tests. All medications that potentially affected the levels of serum thyrotropin or free thyroxin in study patients were detected. RESULTS: 40% (292 of 735) of the patients tested for thyrotropin and 32% (107 of 333) of the patients tested for free thyroxin received potentially interfering medication during the tests. The most common potentially interfering medication was acetylsalicylic acid, but the daily dose was usually low, 100 mg. CONCLUSIONS: The coincidence of potentially interfering medication and thyroid function tests was substantial. On-line hints of drug effects on thyroid function tests might offer valuable decision support to clinicians, but further development of the system is needed to regulate the prevalence of warnings into a clinically optimal level.

Linking patient medication data with laboratory information system.

Dozens of new drugs are taken into clinical use each year. Even if the clinicians were able to learn the most important therapeutic effects of the drugs they prescribe, they would still be unable to remember all of their minor effects. After storing patient related medication data on computerized patient records it is possible to build decision support modules which automatically remind of possible drug influences on laboratory tests and cause alarms or alerts of drug interactions. Medication profiles coded using the Anatomical Therapeutic Chemical-code (ATC-code) constitutes a valuable part of an Electronic Patient Record (EPR). In this paper, we describe the benefits of our system. By building links to commercially available drug and laboratory databases we can automatically inform clinicians on clinically relevant drug influences on laboratory test results.

Development of beta-lactamase-mediated resistance to penicillin in middle-ear isolates of Moraxella catarrhalis in Finnish children, 1978-1993.

The frequency of beta-lactamase production was analyzed in a study of 1,452 strains of Moraxella catarrhalis and 2,738 strains of Haemophilus influenzae isolated from middle-ear fluid of children < 6 years of age at Tampere University Hospital in Tampere, Finland, between 1978 and 1993. In addition, 401 isolates of M. catarrhalis from similar samples collected in different parts of Finland in 1988-1990 were tested for beta-lactamase production; minimal inhibitory concentrations of ampicillin, cefaclor, cephalothin, erythromycin, tetracycline, and trimethoprim-sulfamethoxazole for these strains were determined. These data were compared with figures for the annual consumption of beta-lactam antimicrobials in the community in 1978-1993. A bimodal increase in the proportion of strains of M. catarrhalis producing beta-lactamase was detected: from 0 to 60% in 1978-1983 and from 60% to 80% in 1988-1990. Concurrently with the second increase, the consumption of cephalosporins increased substantially in the community. The frequency of beta-lactamase-producing strains of H. influenzae did not increase between 1978 and 1993.

Using computerized individual medication data to detect drug effects on clinical laboratory tests.

In clinical practice, thousands of drugs are used daily. Clinicians know the therapeutic effects of drugs but other minor drug effects are often ignored either because of inadequate knowledge of these effects or simply because of the limited memory capacity of a human being. This problem can be solved by using a computerized information system, which includes medication data of individual patients as well as information about non-therapeutic drug-effects. One of these non-therapeutic confusing drug effects is the influence of drugs on laboratory tests; a problem that should be taken into account in clinical practice and diagnostics. Other complicating drug effects include drug interactions and patient related adverse drug reactions. In a computerized information system, it is possible to build decision support modules that automatically give alarms or alerts of important drug effects other than therapeutic effects. If these warnings concern laboratory tests they are checked by a laboratory physician and only those with clinical significance are sent to clinicians. Warnings of drug interactions and adverse drug reactions are immediately evaluated by the physician responsible for the treatment. By means of the computerized information system, it is also possible to get better information of current medication practice which in turn gives better chances to agree on common guidelines and enables better quality assurance.

Coding drug effects on laboratory tests for health care information systems.

Drugs interfere with laboratory diagnostics. This interference is not only confusing for clinicians but may lead to wrong diagnoses or treatments as well as unnecessary further tests. However, at the moment the drug-laboratory interferences are usually ignored in patient care because clinicians do not know or remember these properties of drugs. In Turku University Central Hospital we are now able to bring this information automatically available for clinicians by using a computerized system for linking individual patient medication data with laboratory information system. For this purpose, we are building a rule base containing the effects of drugs on laboratory tests. In order that the rule base would give the maximum benefit for all users, even other hospitals, the data included have to be classified and coded properly taking into account the various requirements and needs of all users. In this paper we introduce a coding scheme for classification and coding of drug effects on laboratory tests.

Basic urinalysis and urine culture: Finnish recommendations from the working group on clean midstream specimens.

A recommendation for basic urinalysis and urine culture is published as an attempt to improve the clinical value of urinary tests and to create a system that utilizes laboratory work as sensibly as possible. More clinical background information is needed when basic urinalysis and urine culture is performed in stages. Collection and storage of urine specimens are standardized in addition to used equipment and bacterial culture. Cytological supravital stain improves qualitative and quantitative findings of urine sediment cytology. A close cooperation between central hospital district is necessary and stressed for further bacterial cultures in more complicated microbiological findings.

Finnish recommendation for methods used in urinalysis: results for five-year period.

A recommendation concerning basic urine examinations and bacteriological cultures was published in 1983 in Finland including three clinical indication groups with different screening strategies. Close cooperation between laboratory experts and clinicians as well as much training in urine sediment cytology were essential before the new principle became widely accepted. Decreased workload in laboratories in clinically less significant cases was shown with the use of the full capacity and qualities of complete urinalysis when needed. Standardized test procedures combined with sediment staining improved the clinical efficiency of urine microscopy.

Class specific antibody response to gonococcal infection.

An enzyme immunoassay was used to determine IgM, IgG, and IgA antibodies to gonococcal pili in 68 patients with uncomplicated gonorrhoea, 35 women with pelvic inflammatory disease, and in 115 normal controls. A clear difference in response rate in all three antibody classes between patients with gonorrhoea and healthy controls was evident. Among women with gonorrhoea, the magnitude of antibody response was higher than among men with gonorrhoea, especially in the IgM class. No major differences were found in the overall distribution of serological findings between women with uncomplicated gonorrhoea and those with gonococcal pelvic inflammatory disease. Among this last group, however, high IgM antibody levels in acute phase sera were significantly associated with the isolation of Neisseria gonorrhoeae in the upper genital tract.