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Biomedical subjects

M Kleiber

Publications and source records attributed to M Kleiber.

At least 19 recordsLinked to original sources

High levels of C-reactive protein with low total cholesterol concentrations additively predict all-cause mortality in patients with coronary artery disease.

BACKGROUND: This study aimed to investigate independent and additive predictive effects of raised C-reactive protein (CRP) levels and decreased total cholesterol levels on mortality in patients with chronic coronary artery disease (CAD). Low total cholesterol (TC) levels are associated with worsened survival in chronic and acute diseases. Elevated CRP level is an important predictor of vascular events and mortality in patients with CAD. Potential inhibition of immune activation by circulating lipoproteins could be a link between cholesterol and inflammatory markers. MATERIALS AND METHODS: A group of 387 patients (median age 59 years) with CAD and with or without severe heart failure (HF) were followed for a median of 5.06 years. Serum total cholesterol and CRP concentrations were measured at enrollment. RESULTS: The relationship between lipoproteins, CRP and survival was explored. High CRP concentrations were in significant association with severity of HF and predicted worsened survival in patients with CAD (hazard ratio 5.214, 95% CI 1.762-15.427). The association between CRP levels and mortality was independent of potential confounding factors such as age, body-mass index, severity of HF, smoking habits, hypertension and TC levels. The prediction of mortality by low TC levels was significant (hazard ratio 2.932, 95% CI 1.021-8.422). Furthermore, patients with increased CRP and decreased TC (additive predictive effect) phenotype had 11.714-times higher risk (95% CI 2.619-52.385) of being nonsurvivors than patients with low CRP/high TC. CONCLUSIONS: High CRP levels and low TC concentrations are independent and additive predictors of mortality in patients with CAD. Our data indicate that joint analysis of circulating lipoproteins and inflammatory biomarkers may improve prediction of survival in patients with CAD.

Aged↗

DNA polymorphisms in the tyrosine hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight.

Sudden and unexpected death from myocardial infarction (MI) is one of the most commonly observed findings in forensic medicine. To investigate the biochemical and genetic background of this disease we investigated the genotypes for two polymorphisms associated with hypertension: TH01, a tetrameric microsatellite in the tyrosine hydroxylase gene and the single nucleotide polymorphism C825T in the GNB3 gene in 116 sudden deaths from MI (78 males, 38 females) and in a control group of 137 deaths from natural causes other than MI (52 males, 85 females). For TH01 no correlation with the prevalence of MI was found. For C825T, results were different. While for the male individuals allelic frequencies and genotype distributions were similar in both groups, T-homozygosity was significantly more common in female fatalities from MI than in the female control group (24% versus 7%; Relative Risk 2.29). Nevertheless, neither for TH01 nor for C825T an association with heart weight was found. Thus our results demonstrate that the C825T polymorphism may play a role in the development of myocardial infarctions, at least in females. They also demonstrate that the genetic component in complex diseases like MI may depend on the gender of the patients. As the influence of this polymorphism on arterial blood pressure appears to be relatively small, and G-proteins are involved in numerous intracellular signal cascades it can be speculated that T-homozygosity at this locus might influence the incidence or mortality of cardiovascular disease via hitherto unknown mechanisms.

Adult↗

Persisting fetal microchimerism does not interfere with forensic Y-chromosome typing.

Forensic Y-chromosome typing applies Y-chromosomal polymorphisms to the analysis of male/female mixed stains such as vaginal swabs in rape cases. The sensitivity of this approach exceeds that of cytological techniques combined with autosomal DNA typing. Y-chromosome typing is based on the assumption that Y-chromosomal DNA found in tissue or secretions of women must originate from a male individual, usually the perpetrator. Nevertheless, it was shown recently that fetal cells can migrate into the female body during pregnancy and can persist for decades ("persisting fetal microchimerism"). The body of a woman after a pregnancy with a male embryo can thus display a small fraction of fetal cells with Y-chromosomes. Using high sensitivity PCR protocols (reamplification with nested primers and up to 60 PCR cycles) fetal cells were previously identified in a number of maternal tissues including skin, blood, muscle and solid organs. It is, however, not clear at present, whether these cells can occur in vaginal secretions, and whether they are capable of producing false positive results in forensic Y-chromosome typing. To evaluate these questions, 66 blood samples of women with at least one son and nine vaginal swabs of women without sexual intercourse in the last 2 weeks were amplified for a stretch of the SRY gene. Eight thyroid gland tissues with already established male fetal microchimerism were used as positive control samples. Blood samples of 10 young girls without history of pregnancy were used as negative controls. Using a PCR with 10 ng of extracted DNA and 30 PCR cycles ("routine sensitivity assay") none of the samples yielded positive results. However, in a PCR with 200 ng of extracted DNA and 45 PCR cycles ("high sensibility assay"), 14% of the blood samples of mothers and 33% of the vaginal swabs amplified for SRY. Our results thus show that increasing the sensitivity of the PCR method and the amount of template DNA produce positive results while protocols used for routine Y-chromosomal typing with small amounts of DNA (approximately 10 ng of DNA) and with a limited number of PCR cycles (approximately 30) can clearly eliminate this peril.

Case-Control Studies↗

Assessment of shooting distance on the basis of bloodstain analysis and histological examinations.

A 28-year-old man was shot using a pump-gun. The main question to be resolved was whether the biological stain pattern on the suspect's trousers, and in particular the bloodstains, can provide evidence to assess the shooting distance between the suspect and the position of the victim's body. The biological stain pattern (i.e. bloodstains and brain tissue) showed backspatters from the shot entrance wound on the back of the head, while the victim was lying face down and the suspect was standing close behind his head.

Adult↗

Less is more--length reduction of STR amplicons using redesigned primers.

PCR primers closely flanking the repeat region were redesigned to reduce the amplicon length of the selected STRs down to approximately 100 bp for the shorter alleles (loci HumTH01, D10S2325, DYS19 and DYS391). Highly degraded DNA (e.g. formalin-fixed tissue) and very low amounts of DNA could be more successfully typed using the new redesigned primers compared to the established sequences generating longer amplicons.

Body Fluids↗

Evidence of fetal microchimerism in Hashimoto's thyroiditis.

Fetal microchimerism, the engraftment of fetal progenitor cells into maternal tissues, has been implicated in the etiology of autoimmune diseases. We used PCR analysis to determine whether microchimerism occurred in the thyroid glands of female patients suffering from Hashimoto's disease and thus may be involved in its etiology. PCR amplification was performed from thyroid gland specimens using primers unique to a Y-chromosomal sequence (SRY gene) and primers for a sequence that is Y/X-chromosomal homologous except for a 6-bp deletion in the X-chromosomal sequence (amelogenin). Microchimerism was detected in 8 of 17 Hashimoto patients, but in only 1 of 25 controls (nodular goiters). Both groups were of similar age and had comparable numbers of pregnancies and numbers of sons. All individuals with microchimerism had given birth to at least 1 son. Our results show that microchimerism is significantly more common in Hashimoto patients than in patients suffering from nodular goiter. We therefore suggest that microchimerism might play a role in the development of Hashimoto's disease, although we cannot completely eliminate the hypothesis that microchimerism is just an "innocent bystander" in a process triggered by other mechanisms.

Adult↗

Topology-induced spin frustrations at the Cr(001) surface studied by spin-polarized scanning tunneling spectroscopy

The magnetic structure of the Cr(001) surface was investigated by spin-polarized scanning tunneling spectroscopy by making use of the spin-polarized surface state located close to the Fermi level. Periodic alternations of the intensity of the surface state peak in local tunneling spectra measured above different ferromagnetic terraces separated by monatomic steps confirm the topological antiferromagnetic order of the Cr(001) surface. Screw dislocations cause topology-induced spin frustration, leading to the formation of domain walls with a width of about 120 nm.

Journal Article↗

D18S535, D1S1656 and D10S2325: three efficient short tandem repeats for forensic genetics.

Three short tandem repeat (STR) polymorphisms characterized by PCR product length < 175 bp were investigated. D18S535 and D1S1656 contained a 4 bp unit as basic repeat motif, D10S2325 a 5 bp unit. The heterozygosity rates were 0.76 (D18S535), 0.88 (D10S2325) and 0. 90 (D1S1656), leading to a combined discrimination power of 0.9999. In contrast to D10S2325 and D18S535, which showed a homogeneous repeat array without any variation in the repeat motifs, repeat length and sequence variation was found for D1S1656. Robust typing results could be observed for all three STRs using highly degraded DNA.

Alleles↗

German shepherd dog is suspected of sexually abusing a child.

A rare case of provoked anal penetration of an 11-year-old boy by a male German shepherd dog was confirmed by the results of morphological, serological and molecular genetic investigations. These results were of great importance to refute the suspicion on two adults. Some serious doubts remained in the version of the course of the event as presented by the boy. Some weeks later when confronted by a psychologist, the boy admitted having deliberately stimulated the dog manually and caused the animal to penetrate him.

Anal Canal↗

[Clinical significance of antiphospholipid autoantibodies in lupus erythematosus].

The authors have determined the prevalence of antibodies of cofactor dependent anticardiolipin and beta 2-glycoprotein I and lupus anticoagulant and the frequency of false positive VDRL test in systemic lupus erythematosus. The aim of this retrospective study was to assess the presence of these antibodies and symptoms of antiphospholipid syndrome. The serum samples were examined by modified ELISA method for detecting of cofactor dependent anticardiolipin. The antibodies to beta 2-glycoprotein I were examined by ELISA. The lupus anticoagulant and VDRL test were performed by routine laboratory method. The authors have found that 19 of 58 patients with systemic lupus erythematosus had cofactor dependent anticardiolipin, 10 patients had antibodies to beta 2-glycoprotein I and 4 patients had positive VDRL test. 5 of 34 plasma samples were lupus anticoagulant positive. 19 patients with systemic lupus erythematosus had 14 neuropsychiatric disorders, 9 cardiovascular diseases, 7 thrombocytopenia, 6 histories of recurrent abortion and fetal loss, 5 livedo reticularis and 3 thromboembolic events in all of them had detected antibodies to cofactor dependent anticardiolipin, while these complications were diagnosed in 39 anticardiolipin negative patients much more rarely. The results of this retrospective study suggest that significant association exists between the presence of cofactor dependent anticardiolipin and symptoms of antiphospholipid syndrome in systemic lupus erythematosus.

Antibodies, Antiphospholipid↗

Unusual explanation for the death of a car passenger.

After collision of a car with the left rearside against a steel mast the 19-year-old front seat passenger was found comatose on the seat. CT imaging showed a depression fracture parietal on the left with an intracerebral haemorrhage on the opposite side. The cause of the injury was unknown to the surgeons at the time of operation. Despite neurosurgical intervention the patient died 24 h after the accident. The post-mortem showed an additional depression fracture at the base of the skull in the right temporal region arousing suspicion of an impalement injury. Only inspection of the car by the forensic pathologists revealed the gas pressure telescopic shock absorber to be the cause of the head injury.

Accidents, Traffic↗

Non-lethal penetrating cardiac injury from a crossbow bolt.

Crossbow injuries to the thorax are nowadays uncommon. The type of arrowhead used determines not only the form of entrance wound but often the outcome of these injuries. We report the case of a 38-year-old man who attempted to commit suicide by firing a bolt from a sport crossbow into his heart. Although the bolt penetrated the mediastinum causing a deep intraseptal myocardial lesion and the pre-operative diagnostic procedure delayed the necessary operation, the patient survived.

Adult↗

Tetranucleotide STR system D8S1132: sequencing data and population genetic comparisons.

In the present investigation of the D8S1132 locus 31 selected alleles were sequenced. In total there were 9 distinguishable alleles found to increase in size by regular 4 bp increments from 134 to 170 bp with a repeat array following the pattern (TCTA)n TCA (TCTA)n. One-third of the sequenced alleles exhibited an altered repeat sequence TCTG TCTA at the 3' flanking region of the repeat array. A nomenclature for the designation of D8S1132 alleles is proposed on the basis of this sequence data and in accordance with the ISFH recommendations. The allele distribution of the D8S1132 locus has been investigated in three German populations (Halle-, Münster-, and Wiesbaden area) with frequencies ranging from 0.004 to 0.24. No deviation from Hardy-Weinberg equilibrium could be observed. The heterozygosity was 0.83 and the discrimination power 0.96 for the Halle population.

Alleles↗

DNA typing of epithelial cells after strangulation.

DNA typing was carried out on epithelial cells which were transferred from the hands of the suspect onto the neck of the victim. In an experimental study 16 suspect-victim combinations were investigated for estimating the typing success. Alternatively to an attack against the neck, the upper arm was used for "strangulation". PCR typing was carried out using the short tandem repeat systems (STRs) HumCD4, HumVWF31A (VWA) and Hum-FIBRA (FGA) and the success rate was > 70% for all 3 systems. In most of the cases mixed patterns containing the phenotype of the suspect and the victim were obtained. In a case where strangulation was the cause of death, epithelial cells could be removed from the neck of the victim. The DNA pattern of the suspect could be successfully amplified using four STRs, demonstrating the applicability of this approach for practical casework.

Adult↗

[Accidental coincidence in cause of death?].

Upon the discovery of two deceased persons in close proximity within a short period of time, a death by other than natural causes is first assumed, and only after the elimination of such a cause of death through police investigations as well as an autopsy can a death by natural causes be assumed. The existence of two different natural causes of death in close proximity within a short period of time is extremely rare. In the subject of our autopsy we made two such observations within a short period of time which are presented as casuistry.

Adult↗

Regulation of bipedal stance: dependency on "load" receptors.

According to recent observations, influence of body load has to be taken into account for the neuronal control of upright stance in addition to the systems known to be involved in this regulation (e.g. afferent input from vestibular canals, visual and muscle stretch receptors). The modulation of compensatory leg muscle electromyographic (EMG) responses observed during horizontal body posture indicates the existence of a receptor system which responds to loading of the body against the supporting platform. This receptor should be located within the extensor muscles because a compensatory EMG response and a loading effect on this response was only present following translational, but not rotational impulses. As the EMG responses were identical to those obtained during upright stance, it is argued that these load receptors activate postural reflexes. According to recent observations in the spinal cat, this afferent input probably arises from Golgi tendon organs and represents a newly discovered function of these receptors in the regulation of stance and gait.

Biomechanical Phenomena↗

[Use of rectal temperature-time of death nomograms at the scene of death].

The application of the rectal temperature time of death nomogram at the scene of death by 11 authors from 6 lego-medical institutes resulted in a standard deviation of the differences between nomographic and real death time of +/- 1.3 h in 46 cases (group I) with met requirements and clearly defined points of contact, nevertheless, including 9 cases with a more progressive cooling (0.5 greater than Q greater than or equal to 0.2). In cases with a real death time of more than 4h (N = 26) the standard deviation was +/- 1.0 hours corresponding to permissible variation of 95% of +/- 2.0 hours. Consequently, the permissible variation of 95% was much smaller than that suggested by the nomogram. The nomographic death time interval did not agree with the real one in 5 cases out of additional 30 cases with recognizably unsure points of contact (group II).

Body Temperature Regulation↗