Fatal intoxication with a decalcifying agent containing formic acid.

A fatality caused by ingestion of a decalcifying agent containing formic acid is reported. Quantitative analysis of formic acid in the form of its methyl ester was performed in different body fluids and organ samples using head-space gas chromatography with flame ionization detection. The blood taken at the time of admission to hospital had a concentration of 370.3 microg/ml, which declined to 13.9 microg/ml after 6.5 h of haemodialysis. Post-mortem concentrations were 855.4 microg/ml (heart blood), 2,712 microg/ml (gastric contents), 1128 microg/ml (haemorrhagic fluid from abdominal cavity), 3,051 microg/ml (bile), 2,664 microg/ml (contents of small intestine), 442.7 microg/g (liver) and 542.3 microg/g (kidney). The most important morphological findings for differentiating between oral and respiratory ingestion were ulceration of the oropharynx and the oesophagus as well as extensive necrotic lesions in the stomach and the duodenum without perforation. Death was caused by massive acidosis, haemolysis, bleeding complications, hepatic and renal failure. Toxicological and morphological findings revealed that a considerable amount of formic acid had been ingested orally with a suicidal intention.

Age estimation: the state of the art in relation to the specific demands of forensic practise.

Age estimation in cadavers, human remains and living individuals may clarify issues with significant legal and social ramifications for individuals as well as for the community. In such cases methods for estimating age should fulfil the following specific demands: (1) they must have been presented to the scientific community, as a rule by publication in peer-reviewed journals, (2) clear information concerning accuracy of age estimation by the method should be available, (3) the methods need to be sufficiently accurate and (4) in cases of age estimation in living individuals principles of medical ethics and legal regulations have to be considered. We have identified and summarized the methods that essentially fulfil these specific demands. In childhood and adolescence morphological methods based on the radiological examination of dental and skeletal development are to be recommended. In adulthood, the accuracy of most morphological methods is much reduced. Here a biochemical method based on aspartic acid racemization in dentine provides the most accurate estimates of age, followed by special morphological dental and skeletal methods. The choice of method has to take account of the individual circumstances of each case. Most methods require either the consultation of specialised and trained scientists or an adequate calibration by the "user". Very few attempts have been made to find common standardisation, calibration and evaluation procedures or to develop means of quality assurance for methods of age estimation. Efforts in these directions are necessary to guarantee quality standards and adequate answers to the important legal and social issue of age estimation in forensic medicine.

Quality assurance in age estimation based on aspartic acid racemisation.

Estimates of the age of living and dead individuals, obtained in order to answer legal or social questions, require minimum quality standards in order to guarantee data quality. We present an outline strategy (with recommendations) for the attainment of quality assurance in age estimation based on aspartic acid racemisation. The strategy is based on a definition of minimum standards for laboratories, including documentation of procedures, methodology and levels of expertise, and the formulation of guidelines for intralaboratory and interlaboratory quality control.

Determination of paracetamol (acetaminophen) in different body fluids and organ samples after solid-phase extraction using HPLC and an immunological method.

A solid-phase extraction method routinely used for serum samples was improved and applied to the qualitative and quantitative determination of paracetamol in different body fluids, e.g. blood, urine, cerebrospinal fluid, synovial fluid, vitreous humor, and in tissue samples. A very simple method showed best results: Body fluids were mixed with phenacetine as internal standard and phosphate buffer (pH 6.8). Then protein was precipitated using acetonitrile. After strong centrifugation the supematant was transferred to a preconditioned Bakerbond C18-SPE-column. Elution with methanol without a prior washing step showed best recovery rates. The extracts were investigated using high-performance liquid chromatography with ultraviolet detection, a photometrical and an immunochemical method.

A review of the methodological aspects of aspartic acid racemization analysis for use in forensic science.

Accurate age determination of adult cadavers and human remains is a key requirement in forensic practice. The current morphological methods lack accuracy and precision, require specialist training and are costly. The use of aspartic acid racemization (AAR) in human dentine provides a simple, cost-effective solution and the method can achieve accuracies of +/- 3 years at best. Currently, there are differences in AAR methodology between laboratories which produce different results on the rate of racemization in teeth. These inconsistencies must be resolved if the technique is to be successfully applied to age determinations in forensic cases. This paper reviews the differences in protocol which have been used, discusses how each method will affect the results obtained from AAR analysis and gives recommendations for optimization of the methological protocol as a first step towards international standardization.

[Value of "medication screening" in therapy for chronic pain]. / Stellenwert des "Medikamenten-Screenings" in der Therapie chronischer Schmerzen.

INTRODUCTION: Drug therapy plays often an important role in the treatment of chronic pain. Former studies and also experiences of clinical practice have given evidence, that insufficient patient compliance is a widespread event. Therefore drug screening becomes a significant tool for quality assurance. In the following the methodical and practical aspects of drug screening are described and recommendations for its use in clinical practice are suggested. OBJECTIVE OF DRUG SCREENING: This tool can be used to check the intake of prescribed drugs, to detect hidden taken drugs, to decide whether side effects result of the prescribed medication or not and to support a withdrawal therapy. PRACTICAL BASICS AND INTERPRETATION OF THE FINDINGS: Drug screening presupposes an informed patient, who consents to the investigation. Otherwise confidence is risked and the handling with unexpected results is not possible any more. Testing of urine has the advantage of a non invasive procedure and makes use of the reservoir of the bladder. A close co-operation and good communication between therapist and laboratory prevents misinterpretations, which might result from inaccurate formulated questions or methodical limitations, for instance because of cross reacting substances or a too insensitive detection level for the respective drug. The finding must primary bee used to value the therapy and improve the compliance but can not prove the patient himself. CONCLUSIONS: Even if the value of drug screening is not prospectively investigated until now, clinical experiences reveals it is as powerful tool for monitoring effectiveness and side effects of pharmacotherapy of pain and also of patient compliance which the prescribed drug regimes.

Effects of nicotine gum on F waves in non-smokers.

The effects of chewing gum, containing 0 and 4 mg nicotine, on F waves were studied in healthy volunteers in a repeated measure design. F responses were recorded from the abductor pollicis brevis muscle following stimulation of the median nerve at the wrist. The persistence and various amplitude measures were analysed. Chewing a 4 mg nicotine gum, with a considerable rise in systemic nicotine (6.4-37.4 ng/ml), failed to produce significant effects on F wave parameters in relation to the placebo baseline. The analysis of different F wave amplitude ranges, however, revealed significant nicotine-induced changes: a dose-related decrease of F responses > or = 500 microV and an increase of F waves between 200-290 microV. This may be due to an activation of Renshaw cells in the spinal cord.

Identification of osteocalcin as a permanent aging constituent of the bone matrix: basis for an accurate age at death determination.

Age at death determination based on aspartic acid racemization in dentin has been applied successfully in forensic odontology for several years now. An age-dependent accumulation of D-aspartic acid has also recently been demonstrated in bone osteocalcin, one of the most abundant noncollagenous proteins of the organic bone matrix. Evaluation of these initial data on in vivo racemization of aspartic acid in bone osteocalcin was taken a step further. After purification of osteocalcin from 53 skull bone specimens, the extent of aspartic acid racemization in this peptide was determined. The D-aspartic acid content of purified bone osteocalcin exhibited a very close relationship to age at death. This confirmed identification of bone osteocalcin as a permanent, 'aging' peptide of the organic bone matrix. Its D-aspartic acid content may be used as a measure of its age and hence that of the entire organism. The new biochemical approach to determination of age at death by analyzing bone is complex and demanding from a methodologic point of view, but appears to be superior in precision and reproducibility to most other methods applicable to bone.

Screening and identification of sumatriptan and its main metabolite by means of thin-layer chromatography, ultraviolet spectroscopy and gas chromatography/mass spectrometry.

Sumatriptan (CAS 103628-46-2, 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide++ +), a substance for treatment of acute migraine attacks, and its main metabolite are investigated by thinlayer chromatography (TLC), ultraviolet spectroscopy, and gas chromatography/mass spectrometry (GC/MS). The resulting analytical data (correlated hRf-values, UV solvent spectra, remission spectra, GC retention indices, and electron impact (EI) mass spectra) including an extraction procedure and different derivatization methods are presented. Their applicability is described for urine analysis.

Age estimation in biopsy specimens of dentin.

Determination of age at death on the basis of aspartic acid racemization in dentin is one of the most reproducible and accurate methods. In Germany, age estimation by this method has so far generally not been applied to living persons, since the extraction of a tooth exclusively for age estimation when it is not medically indicated is regarded as ethically and legally problematic. The development of a biopsy technique applicable to dentin took place against this background. Testing the technique and analysis of dentinal biopsy specimens revealed that the biopsy technique is a low-risk procedure that causes only minor discomfort to the affected person. It is readily practicable and facilitates standardized specimen removal. The relationship between the extent of aspartic acid racemization in dentinal biopsy specimens and age is very close, facilitating age estimation. A prerequisite for accurate results is the performance of biopsies under strictly standardized conditions. If this is guaranteed, age determination on the basis of aspartic acid racemization in dentinal biopsy specimens appears to be superior in precision to most other methods in living persons and can be used for all age groups.

Estimation of age at death based on aspartic acid racemization in noncollagenous bone proteins.

Age at death determination based on the extent of aspartic acid racemization in dentin has been reported to be highly accurate and reproducible. To test the applicability of this method to human bone, aspartic acid racemization in noncollagenous proteins of bone was investigated. A close relationship was found between age at death and the extent of aspartic acid racemization in osteocalcin, the most abundant noncollagenous protein of the organic bone matrix. Our findings indicate that osteocalcin is a permanent, 'aging' constituent of the organic bone matrix whose D-aspartic acid content increases with age because of in vivo racemization. Thus, the extent of aspartic acid racemization in bone osteocalcin is a measure of the age of the peptide and hence of the entire organism. The relationship between age at death and the extent of aspartic acid racemization in purified bone osteocalcin appears to be close enough to serve as a basis for determination of age at death in forensic medicine.

Aspartic acid racemization in intervertebral discs as an aid to postmortem estimation of age at death.

We investigated whether measurement of aspartic acid racemization in intervertebral discs (IVD) could be used in the postmortem estimation of age at death. The extent of aspartic acid racemization in IVD tissues was found to increase with age. The rate of racemization turned out to be much higher in the nucleus pulposus than in the annulus fibrosus. The relation between age and the D-aspartic acid content in the anterior peripheral annulus fibrosus of IVD was close enough to allow postmortem estimation of age at death based on the extent of aspartic acid racemization in this tissue.

Postmortem estimation of age at death based on aspartic acid racemization in dentin: its applicability for root dentin.

The extent of aspartic acid racemization in total dentin and in dentin protein fractions from the roots of third molars was determined. In several cases coronal dentin was also investigated. The results of other authors, according to which the racemization of aspartic acid in root dentin apparently proceeds differently than in coronal dentin, could be confirmed. Consequently, the data published so far on age determination based on the extent of aspartic acid racemization in coronal dentin and the "entire dentin of longitudinal sections" cannot be applied to root dentin. In total root dentin and the acid soluble protein of root dentin, a close relationship was observed between the extent of aspartic acid racemization and age. Accordingly, estimation of age at death based on aspartic acid racemization in dentin is also possible for root dentin, apparently with good results. This is important particularly in those cases where a large portion of the coronal dentin is absent, for instance following dental treatment. In the investigation of root dentin, regression equations specific for root dentin must be employed in the estimation of age at death. Corresponding equations for third molars were calculated.

Measurement of digitalis-glycoside levels in ocular tissues: a way to improve postmortem diagnosis of lethal digitalis-glycoside poisoning? II. Digitoxin.

Postmortem digitoxin levels in the choroid-retina and vitreous humor of patients who had undergone digitoxin therapy (therapeutic group) and in one case of suicidal digitoxin poisoning were measured and compared with levels in femoral vein blood, myocardium, kidney and liver. The results were interpreted in light of the medical history of each patient. The digitoxin level in the choroid-retina of the single case of suicidal poisoning was far higher than the choroid-retinal levels in the therapeutic group. In the latter, variation in choroid-retinal levels was comparable to that in the other tissues. In cases where the choroid-retina of the right and left eyes were examined, digitoxin levels in both eyes were essentially equal. There was no indication of significant changes in choroid-retinal levels due to postmortem diffusion of digitoxin into the vitreous body. Based on these results, determination of digitoxin levels in the choroid-retina could contribute to improving postmortem diagnosis of lethal digitoxin poisoning.

Measurement of digitalis-glycoside levels in ocular tissues: a way to improve postmortem diagnosis of lethal digitalis-glycoside poisoning? I. Digoxin.

Prompted by animal studies reporting the accumulation of digitalis-glycosides in ocular tissues, we investigated whether measurement of digoxin levels in human ocular tissues can improve the postmortem diagnosis of lethal digoxin intoxication. Digoxin was measured in the vitreous humor and choroid-retina of patients who had received in-patient treatment with digoxin prior to death (therapeutic group) and in a single case of suicidal intoxication. The results were compared with the digoxin levels in the femoral vein blood, myocardium, kidney and liver, and evaluated in light of the medical history of each patient. In the therapeutic group the mean digoxin level was higher in the choroid-retina than in other tissues and body fluids. The range of variation in levels in the choroid-retina following therapeutic doses was comparable to that in the other tissues. An extremely high level of digoxin was present in the choroid-retina in the case of suicidal intoxication. In all cases, levels in the vitreous humor were very low compared to those in the choroid-retina. Hence, it is unlikely that significant distortion of choroid-retinal levels occurs due to postmortem diffusion of digoxin into the vitreous body. Our results indicate that measurement of digoxin levels in the choroid-retina can aid the postmortem diagnosis of lethal digoxin intoxication.

The extent of aspartic acid racemization in dentin: a possible method for a more accurate determination of age at death?

In the current study the objective was to find to what extent a reliable determination of age at death is made possible by establishing the degree of aspartic acid racemization in the dentin of teeth. The results of the investigation of 46 teeth are in agreement with the values found by other authors. The method presented makes a reproducible and accurate estimation of age possible. We intend to elaborate and improve this promising method for determination of age at death. The relevant points are presented here.