Klaus Pueschel

Impaired gastric acidification negatively affects calcium homeostasis and bone mass.

Activation of osteoclasts and their acidification-dependent resorption of bone is thought to maintain proper serum calcium levels. Here we show that osteoclast dysfunction alone does not generally affect calcium homeostasis. Indeed, mice deficient in Src, encoding a tyrosine kinase critical for osteoclast activity, show signs of osteopetrosis, but without hypocalcemia or defects in bone mineralization. Mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells, have the expected defects in gastric acidification but also secondary hyperparathyroidism and osteoporosis and modest hypocalcemia. These results suggest that alterations in calcium homeostasis can be driven by defects in gastric acidification, especially given that calcium gluconate supplementation fully rescues the phenotype of the Cckbr-mutant mice. Finally, mice deficient in Tcirg1, encoding a subunit of the vacuolar proton pump specifically expressed in both osteoclasts and parietal cells, show hypocalcemia and osteopetrorickets. Although neither Src- nor Cckbr-deficient mice have this latter phenotype, the combined deficiency of both genes results in osteopetrorickets. Thus, we find that osteopetrosis and osteopetrorickets are distinct phenotypes, depending on the site or sites of defective acidification (pages 610–612).

Use of PCR–RFLP for differentiation of calliphorid larvae (Diptera, Calliphoridae) on human corpses

Blowfly larvae found on human corpses are important for the estimation of the postmortem interval (PMI) and other questions of forensic relevance. Some of these species are difficult to differentiate morphologically, therefore a molecular method was elaborated for species identification. Specific fragments of the COI and COII region of the mitochondrial DNA (mtDNA) were amplified followed by digestion with different restriction enzymes. Using a 1.3 kb fragment, identification of Lucilia sericata, Calliphora vicina and Calliphora vomitoria was possible by digestion with only one restriction enzyme using either DraI or HinfI. Furthermore, we sequenced 349 bp (a part of the COI and COII regions) from the same three species and found 34 nucleotide distinctions between C. vicina and L. sericata, 30 between C. vomitoria and L. sericata and 15 between the two Calliphora species. These results aid in quick identification of species used for estimation of PMI.

Age- and sex-related changes of humeral head microarchitecture: Histomorphometric analysis of 60 human specimens†

Fractures of the humeral head are frequent and will further increase due to demographic changes. Prior to operative fracture treatment, the regional differences of bone quality, especially of elderly people, have to be carefully considered to assure stable implant fixation. However, conclusive data concerning the variation of histomorphometric parameters are still lacking. Consequently, the purpose of this study was to analyze the age‐ and sex‐related changes in bone microarchitecture. For that reason, 60 proximal humeri were harvested from patients at autopsy. Twelve regions of interest (ROI) were defined for each centered coronar humeral head slice and the specimens were subjected to radiographic, histological, and histomorphometric analyses. We could demonstrate that in contrast to men, women over 60 years of age had a significant age‐related decrease in bone mass. The most prominent decrease was observed in the region of the greater tuberosity, which represents an osteoporotic fracture site. The most superior and medially located part of the centered coronar humeral head slice showed, independent from age and sex, the highest bone mass and can therefore be considered as the best location for subchondral screw placement. Taken together, our study revealed distinct sex‐related changes of the humeral head bone microarchitecture with aging, which should be considered in implant positioning.

Biomechanical Evaluation of 3 Stabilization Methods on Acromioclavicular Joint Dislocations

Background: Traumatic acromioclavicular (AC) joint dislocations can be addressed with several surgical stabilization techniques. The aim of this in vitro study was to evaluate biomechanical features of the native joint compared with 3 different stabilization methods: locking hook plate (HP), TightRope (TR), and bone anchor system (AS). Hypothesis: The HP provides higher stiffness than the anatomic reconstruction techniques. Study Design: Controlled laboratory study. Methods: A new biomechanical in vitro model of the AC joint was used to analyze joint stability after surgical repair (HP, TR, and AS). Eighteen cadaveric specimens were randomized for bone density and diameter in the midclavicle section. Joint stiffness was measured by applying an axial load and a defined physiological range of motion for internal and external rotations and upward and downward rotations. Data were recorded at 3 stages: for the native joint after dissecting the AC ligaments, directly after repair, and after axial cyclic loading (1000 cycles with 20 and 70 N at 1 Hz). To evaluate which implant mimics physiological joint properties best, axial stiffness of vertical stability was assessed in combination with rotation. Finally, static loading in the superior direction was applied until failure of the joints occurred. Results: Axial stiffness of the TR and AS groups was 2-fold higher than for the HP group and the native joint (67.1, 66.1, and 22.5 N/mm, respectively; P < .004). Decreased load-to-failure rates were recorded in the HP group compared with the TR and AS groups (248.9 ± 72.7, 832.0 ± 401.4, and 538.0 ± 166.1 N, respectively). The stiffness of the rotations was not significantly different between the treatment methods but was lower in horizontal and downward rotations compared with the native state. Thus, native AC ligaments contributed a significant share to joint stiffness. Conclusion: The TR and AS groups demonstrated higher vertical load capacity. Compared with the TR and AS, the HP demonstrated an axial stiffness closest to the native joint. For restoring physiological properties, reconstruction of the AC ligaments may be necessary. Clinical Relevance: The results show different biomechanical properties of the HP and anatomic reconstructions.

Cardiac injuries in car occupants in fatal motor vehicle collisions--an autopsy-based study.

Motor vehicle accidents contribute widely to population morbidity and mortality around the world, and cardiac injuries are a major factor determining outcome. Autopsy reports from 380 motor vehicle occupants who died in motor vehicle crashes in Adelaide, Australia, and Hamburg, Germany, over a 6-year period were reviewed, analysing the presence and type of cardiac injuries and their correlation with factors such as crash type, presence of seatbelt/airbag and vehicle speed as well as with the presence of other injuries which might predict the presence of cardiac injuries in a clinical setting. 21.1% had cardiac injuries identified macroscopically autopsy or histology. Cardiac injuries were the only cause of death or contributed to a fatal outcome in 76% of these cases. Sternal fractures and left-sided serial rib fractures were predictive of cardiac injury.

Microarchitecture of the Radial Head and Its Changes in Aging

Fractures of the radial head are common; however, it remains to be determined whether the radial head has to be considered as a typical location for fractures associated with osteoporosis. To investigate whether the human radial head shows structural changes during aging, we analyzed 30 left and 30 right human radial heads taken from 30 individuals. The specimens taken from the left side were analyzed by peripheral quantitative computed tomography (pQCT) and micro-CT. The specimens taken from the right elbow joint were analyzed by radiography and histomorphometry. In these specimens pQCT revealed a significant decrease of total and cortical bone mineral density (BMDto BMDco) with aging, regardless of sex. Histomorphometry revealed a significant reduction of cortical thickness (Ct.Th), bone volume per tissue volume (BV/TV), and trabecular thickness (Tb.Th) in male and female specimens. In this context, mean BV/TV and mean trabecular number (Tb.N) values were significantly lower and, accordingly, mean trabecular separation (Tb.Sp) was significantly higher in female samples. The presented study demonstrates that the radial head is a skeletal site where different age- and sex-related changes of the bone structure become manifest. These microarchitectural changes might contribute to the pathogenesis of radial head fractures, especially in aged female patients where trabecular parameters (BMDtr and Tb.Sp) change significantly for the worse compared to male patients.

Quantitative analysis of victim demographics and injury characteristics at a metropolitan Medico-Legal Center.

For the timeframe of February 1st, 2003 until December 31st, 2005, all forensic medical experts at the Medico-Legal Center of the Institute of Legal Medicine in Hamburg, Germany, completed a standardized questionnaire for every consenting surviving violence victim (n=2733) age 14 and older. Central to the quantitative analysis of the data collected was the extraction of specific injury characteristics from the sample population. A correlation was demonstrated between injury typologies and four possible perpetrator-victim constellations, each of which was subcategorized into sexual and non-sexual assaults.

Osteologische Virtopsie einer Moorleiche aus der frühen Eisenzeit (ca. 650 v. Chr.)

Wir freuen uns schon auf die Abbildungen zu Ihrem interesanten Fall! Prof. Dr. K. Püschel pueschel@uke.uni-hamburg.de Rechtsmedizin 2007 · 17:223–224 DOI 10.1007/s00194-007-0453-z Online publiziert: 23. Juni 2007

Phenotypic Diversity in Chondromyxoid Fibroma Reveals Differentiation Pattern of Tumor Mimicking Fetal Cartilage Canals Development : An Immunohistochemical Study

Chondromyxoid fibroma represents a rare benign cartilaginous tumor of young patients occurring in a subcortical metaphyseal location. The histogenesis of chondromyxoid fibroma has not yet been postulated, even though the conventional histology and recent immunohistochemical studies on phenotype of the mesenchymal cells and extracellular matrix components suggested its origin in immature cartilage. Therefore, we wished to compare the morphological pattern of immature cartilage tissue with chondromyxoid fibroma to investigate a possible developmental counterpart of chondromyxoid fibroma. Archival paraffin-embedded tissues from 4 fetal femora and 10 cases of chondromyxoid fibroma were analyzed simultaneously using histochemistry (safranin O) and established immunohistochemical antibodies (CD34, CD163, and smooth muscle actin). Vascularized cartilage canals growing into the fetal cartilage from the perichondrium displayed characteristic glomeruloid structures with central arterioles within the immature mesenchymal stroma and numerous superficial sinusoidal blood vessels accompanied by macrophage infiltration. Similarly, each case of chondromyxoid fibroma demonstrated admixture of two characteristic components: immature fibrous tissue of vascularized stroma with accumulation of macrophages in areas of superficial sinusoidal proliferation, and variable amounts of lobulated chondroid tissue. Based on the observed substantial morphological similarity between the cartilage canals and chondromyxoid fibroma, we suggest that the chondromyxoid fibroma represents a neoplasm originating from or mimicking the fetal cartilage canals within the immature cartilage.

Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy

Mutations in the SCN8A gene encoding the neuronal voltage-gated sodium channel Nav1.6 are known to be associated with epileptic encephalopathy type 13. We identified a novel de novo SCN8A mutation (p.Phe360Ala, c.1078_1079delTTinsGC, Exon 9) in a 6-year-old girl with epileptic encephalopathy accompanied by severe juvenile osteoporosis and multiple skeletal fractures, similar to three previous case reports. Skeletal assessment using dual energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) and serum analyses revealed a combined trabecular and cortical bone loss syndrome with elevated bone resorption. Likewise, when we analyzed the skeletal phenotype of 2week-old Scn8a-deficient mice we observed reduced trabecular and cortical bone mass, as well as increased osteoclast indices by histomorphometric quantification. Based on this cumulative evidence the patient was treated with neridronate (2mg/kg body weight administered every 3months), which fully prevented additional skeletal fractures for the next 25months. Taken together, our data provide evidence for a negative impact of SCN8A mutations on bone mass, which can be positively influenced by anti-resorptive treatment.