Background Determination of the duration of malnutrition episodes in children or adults, especia... more Background Determination of the duration of malnutrition episodes in children or adults, especially to distinguish between acute and chronic malnutrition, is an important part of criminal law assessment. In a previous study a method to reliably detect starvation episodes by serial analysis of stable nitrogen and carbon isotopes in hair samples which can be non-invasively sampled was developed Sequential analysis of
Background Determination of the duration of malnutrition episodes in children or adults, especia... more Background Determination of the duration of malnutrition episodes in children or adults, especially to distinguish between acute and chronic malnutrition, is an important part of criminal law assessment. In a previous study a method to reliably detect starvation episodes by serial analysis of stable nitrogen and carbon isotopes in hair samples which can be non-invasively sampled was developed Sequential analysis of isotopic ratios of hair strands of all patients could be related to the respective body mass index (BMI) of each patient. Materials and Methods In this follow-up study a further seven patients and one control subject were recruited to validate this method. Results The hypothesis concerning a diachronic change in δ15N and δ13C during therapy was verified in this study. Conclusion In this study the application of stable isotopes with serial hair analysis in forensic studies with regard to malnutrition or starvation cases of children and adults has been verified. An unbiased biomarker to reliably determine the onset and duration of chronic or acute starvation in order to set a timeframe for each individual malnutrition neglect case has been established which is independent of age, race, geographical location and individual metabolism.
Stable strontium isotope ratios in archaeological finds have frequently been used to determine th... more Stable strontium isotope ratios in archaeological finds have frequently been used to determine their place of origin, in order to reconstruct migration and trade. Peat bogs offer favourable burial conditions for the preservation of organic remains such as woollen textiles and leather by a natural tanning process. However, these finds are impregnated by peat substances including contaminant strontium which is likely to mask the original (87)Sr/(86)Sr isotopic ratio of the specimens. In this paper, we present a pilot study analysing stable strontium isotopic ratios from Iron Age textile and leather finds from the Thorsberg peat bog, focusing on a sample processing method which permits the quantitative removal of contaminating strontium from the specimens.
During an excavation headed by the German Institute for Archaeology, Cairo, at the tombs of the n... more During an excavation headed by the German Institute for Archaeology, Cairo, at the tombs of the nobles in Thebes-West, Upper Egypt, three types of tissues from different mummies were sampled to compare 13 well known rehydration methods for mummified tissue with three newly developed methods. Furthermore, three fixatives were tested with each of the rehydration fluids. Meniscus (fibrocartilage), skin, and a placenta were used for this study. The rehydration and fixation procedures were uniform for all methods. The stains used were standard hematoxylin and eosin, elastica van Gieson, periodic acid-Schiff, and Grocott, and five commercially obtained immunohistochemical stains including pancytokeratin, vimentin, alpha-smooth-muscle-actin, basement membrane collagen type IV, and S-100 protein. The sections were examined by transmitted light microscopy. Our study showed that preservation of the tissue is dependent on the quality and effectiveness of the combination of the rehydration and fixation solutions, and that the quality of the histological and histochemical stains is dependent on the tissue quality. In addition, preservation of the antigens in the tissues is dependent on tissue quality, and fungal permeation had no influence on the tissue. Finally, the results are tissue specific. For placenta the best solution combination was Sandison and solution III (both fixed with formaldehyde) while results for skin were best with Ruffer I (using formaldehyde and Schaffer as fixatives), Grupe et al. (using formaldehyde as a fixative) and solution III (in combination with formaldehyde and Bouin fixatives). Ruffer II (using formaldehyde as a fixative) and solution III (in combination with Schaffer fixative) gave the best results for fibrocartilage.
SQ109, an asymmetrical diamine, is a novel anti-TB drug candidate. This first study in patients w... more SQ109, an asymmetrical diamine, is a novel anti-TB drug candidate. This first study in patients was done to determine safety, tolerability, pharmacokinetics and bacteriological effect of different doses of SQ109 alone and in combination with rifampicin when administered over 14 days. Smear-positive pulmonary TB patients were randomized into six groups of 15 to receive once-daily oral treatment with 75, 150 or 300 mg of SQ109, rifampicin (10 mg/kg body weight), rifampicin plus 150 mg of SQ109, or rifampicin plus 300 mg of SQ109 for 14 days. Patients were hospitalized for supervised treatment, regular clinical, biochemical and electrocardiographic safety assessments, pharmacokinetic profiling and daily overnight sputum collection. SQ109 was safe and generally well tolerated. Mild to moderate dose-dependent gastrointestinal complaints were the most frequent adverse events. No relevant QT prolongation was noted. Maximum SQ109 plasma concentrations were lower than MICs. Exposure to SQ109 (AUC0-24) increased by drug accumulation upon repeated administration in the SQ109 monotherapy groups. Co-administration of SQ109 150 mg with rifampicin resulted in decreasing SQ109 exposures from day 1 to day 14. A higher (300 mg) dose of SQ109 largely outweighed the evolving inductive effect of rifampicin. The daily fall in log cfu/mL of sputum (95% CI) was 0.093 (0.126-0.059) with rifampicin, 0.133 (0.166-0.100) with rifampicin plus 150 mg of SQ109 and 0.089 (0.121-0.057) with rifampicin plus 300 mg of SQ109. Treatments with SQ109 alone showed no significant activity. SQ109 alone or with rifampicin was safe over 14 days. Upon co-administration with rifampicin, 300 mg of SQ109 yielded a higher exposure than the 150 mg dose. SQ109 did not appear to be active alone or to enhance the activity of rifampicin during the 14 days of treatment.
Background Determination of the duration of malnutrition episodes in children or adults, especia... more Background Determination of the duration of malnutrition episodes in children or adults, especially to distinguish between acute and chronic malnutrition, is an important part of criminal law assessment. In a previous study a method to reliably detect starvation episodes by serial analysis of stable nitrogen and carbon isotopes in hair samples which can be non-invasively sampled was developed Sequential analysis of
Background Determination of the duration of malnutrition episodes in children or adults, especia... more Background Determination of the duration of malnutrition episodes in children or adults, especially to distinguish between acute and chronic malnutrition, is an important part of criminal law assessment. In a previous study a method to reliably detect starvation episodes by serial analysis of stable nitrogen and carbon isotopes in hair samples which can be non-invasively sampled was developed Sequential analysis of isotopic ratios of hair strands of all patients could be related to the respective body mass index (BMI) of each patient. Materials and Methods In this follow-up study a further seven patients and one control subject were recruited to validate this method. Results The hypothesis concerning a diachronic change in δ15N and δ13C during therapy was verified in this study. Conclusion In this study the application of stable isotopes with serial hair analysis in forensic studies with regard to malnutrition or starvation cases of children and adults has been verified. An unbiased biomarker to reliably determine the onset and duration of chronic or acute starvation in order to set a timeframe for each individual malnutrition neglect case has been established which is independent of age, race, geographical location and individual metabolism.
Stable strontium isotope ratios in archaeological finds have frequently been used to determine th... more Stable strontium isotope ratios in archaeological finds have frequently been used to determine their place of origin, in order to reconstruct migration and trade. Peat bogs offer favourable burial conditions for the preservation of organic remains such as woollen textiles and leather by a natural tanning process. However, these finds are impregnated by peat substances including contaminant strontium which is likely to mask the original (87)Sr/(86)Sr isotopic ratio of the specimens. In this paper, we present a pilot study analysing stable strontium isotopic ratios from Iron Age textile and leather finds from the Thorsberg peat bog, focusing on a sample processing method which permits the quantitative removal of contaminating strontium from the specimens.
During an excavation headed by the German Institute for Archaeology, Cairo, at the tombs of the n... more During an excavation headed by the German Institute for Archaeology, Cairo, at the tombs of the nobles in Thebes-West, Upper Egypt, three types of tissues from different mummies were sampled to compare 13 well known rehydration methods for mummified tissue with three newly developed methods. Furthermore, three fixatives were tested with each of the rehydration fluids. Meniscus (fibrocartilage), skin, and a placenta were used for this study. The rehydration and fixation procedures were uniform for all methods. The stains used were standard hematoxylin and eosin, elastica van Gieson, periodic acid-Schiff, and Grocott, and five commercially obtained immunohistochemical stains including pancytokeratin, vimentin, alpha-smooth-muscle-actin, basement membrane collagen type IV, and S-100 protein. The sections were examined by transmitted light microscopy. Our study showed that preservation of the tissue is dependent on the quality and effectiveness of the combination of the rehydration and fixation solutions, and that the quality of the histological and histochemical stains is dependent on the tissue quality. In addition, preservation of the antigens in the tissues is dependent on tissue quality, and fungal permeation had no influence on the tissue. Finally, the results are tissue specific. For placenta the best solution combination was Sandison and solution III (both fixed with formaldehyde) while results for skin were best with Ruffer I (using formaldehyde and Schaffer as fixatives), Grupe et al. (using formaldehyde as a fixative) and solution III (in combination with formaldehyde and Bouin fixatives). Ruffer II (using formaldehyde as a fixative) and solution III (in combination with Schaffer fixative) gave the best results for fibrocartilage.
SQ109, an asymmetrical diamine, is a novel anti-TB drug candidate. This first study in patients w... more SQ109, an asymmetrical diamine, is a novel anti-TB drug candidate. This first study in patients was done to determine safety, tolerability, pharmacokinetics and bacteriological effect of different doses of SQ109 alone and in combination with rifampicin when administered over 14 days. Smear-positive pulmonary TB patients were randomized into six groups of 15 to receive once-daily oral treatment with 75, 150 or 300 mg of SQ109, rifampicin (10 mg/kg body weight), rifampicin plus 150 mg of SQ109, or rifampicin plus 300 mg of SQ109 for 14 days. Patients were hospitalized for supervised treatment, regular clinical, biochemical and electrocardiographic safety assessments, pharmacokinetic profiling and daily overnight sputum collection. SQ109 was safe and generally well tolerated. Mild to moderate dose-dependent gastrointestinal complaints were the most frequent adverse events. No relevant QT prolongation was noted. Maximum SQ109 plasma concentrations were lower than MICs. Exposure to SQ109 (AUC0-24) increased by drug accumulation upon repeated administration in the SQ109 monotherapy groups. Co-administration of SQ109 150 mg with rifampicin resulted in decreasing SQ109 exposures from day 1 to day 14. A higher (300 mg) dose of SQ109 largely outweighed the evolving inductive effect of rifampicin. The daily fall in log cfu/mL of sputum (95% CI) was 0.093 (0.126-0.059) with rifampicin, 0.133 (0.166-0.100) with rifampicin plus 150 mg of SQ109 and 0.089 (0.121-0.057) with rifampicin plus 300 mg of SQ109. Treatments with SQ109 alone showed no significant activity. SQ109 alone or with rifampicin was safe over 14 days. Upon co-administration with rifampicin, 300 mg of SQ109 yielded a higher exposure than the 150 mg dose. SQ109 did not appear to be active alone or to enhance the activity of rifampicin during the 14 days of treatment.
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Papers by A. Mekota