Postmortem computed tomography (PMCT) and autopsy in deadly gunshot wounds--a comparative study.

INTRODUCTION: Postmortem computed tomography (PMCT) data in gunshot-related death were evaluated by two reader groups and compared to the gold standard autopsy for the determination of forensic pathology criteria. MATERIALS AND METHODS: Reader group I consisted of two board-certified radiologists whereas one board-certified radiologist and one board-certified forensic pathologist formed group II. PMCT data of 51 gunshot-related deaths were evaluated for the forensic pathology criteria number of gun shots, localization of gunshot injury, caliber, and direction of the gunshot differentiating between entry and exit wound as well as associated injury to surrounding tissue. The results of both reader groups were compared to the each other and to autopsy findings considered as gold standard. RESULTS: Reader groups I and II and as gold standard the autopsy evaluation showed in general a good correlation between all results. The overall discrepancy rate was 12/51 (23.4%) cases for group I and 8/51 (15.6%) for group II. DISCUSSION: Ultimately, the designated reader is able to draw the following conclusion from the presented data. At first, physical autopsy is better than PMCT regarding the localization of most gunshot injuries. Second, PMCT presents with better results than physical autopsy in locating fragmented bullets/fragment clouds, and finally, PMCT results of two radiologists were equivalent to the results of one evaluating radiologist and one pathologist with the exception of caliber assessment. However, referring to the pure numbers, the slight but not significant difference in the overall discrepancy rate of both reader groups might indicate the advantage of combining expertise in evaluating imaging in cases of gunshot-related death.

[Classification of periprosthetic shoulder fractures]. / Klassifikation periprothetischer Schulterfrakturen.

The key targets in the treatment of periprosthetic humeral fractures (PHF) are the preservation of bone, successful bony consolidation and provision of a stable anchoring of the prosthesis with the major goal of restoring the shoulder-arm function. A substantial problem of periprosthetic shoulder fractures is the fact that treatment is determined not only by the fracture itself but also by the implanted prosthesis and its function. Consequently, the exact preoperative shoulder function and, in the case of an implanted anatomical prosthesis, the status and function of the rotator cuff need to be assessed in order to clarify the possibility of a secondarily occurring malfunction. Of equal importance in this context is the type of implanted prosthesis. The existing classification systems of Wright and Cofield, Campbell et al., Groh et al. and Worland et al. have several drawbacks from a shoulder surgeon's point of view, such as a missing reference to the great variability of the available prostheses and the lack of an evaluation of rotator cuff function. The presented 6­stage classification for the evaluation of periprosthetic fractures of the shoulder can be considered just as simple or complex to understand as the classification of the working group for osteosynthesis problems (AO, Arbeitsgemeinschaft für Osteosynthesefragen), depending on the viewpoint. From our point of view the classification presented here encompasses the essential points of the existing classification systems and also covers the otherwise missing points, which should be considered in the assessment of such periprosthetic fractures. The classification presented here should provide helpful assistance in the daily routine to find the most convenient form of therapy.

Dynamic in vitro analysis of tractile forces of the anterior cruciate ligament (ACL) transplant using patellar and semitendinosus muscle tendon: a cadaver study.

PURPOSE: The presented biomechanical study focused on the in vitro analysis of tractile forces working on the anterior cruciate ligament (ACL) and the ACL transplants, respectively, using a semitendinosus and/or patellar tendon during a passive flexion-extension movement (150-0°). MATERIAL AND METHODS: Overall, 15 fresh frozen human knee joint pairs were examined. At first during arthroscopy, the tibial insertion of the ACL was drilled using a special hollow drill. Thereby, a bone cylinder was exposed at which a dynamometer was attached to enable for direct registration of tractile forces on the ACL via the connection between ACL-dynamometer and computer. The ACL transplant was fixed at the femur using a so-called endo-button, whereas the dynamometer was attached to the tibial end of the ACL transplant. The dynamic part of the examination was performed using the knee kinemator device developed by Plitz and Wirth et al. using different preload. RESULTS: The curves of the tractile forces of the ACL were qualitatively homogeneous with only low force values in the middle flexion position, whereas during maximum flexion and extension the forces increased reaching a maximum in the 0° position. Also, in testing the ACL transplants a force decrease between 0 and 50° flexion was recognized with even greater forces resulting at the 150° position depending on the anterior position of the femoral drill channel for implanting the ACL transplant. The amount of pre-loading showed no influence on the form of the tractile force curve. However, by enhancing the preload to 70 N, the maximal force in the ACL transplant increased significantly. CONCLUSION: The tractile forces assessed within the ACL during passive flexion movements between 10 and 90° were not greater than the forces measured in the ACL transplants. Thus, the clinical consequence is that in the early postoperative phase passive mobilization might be performed in this motion range without putting the ACL transplant at risk for damage.

In vivo evaluation of the kinematics of the long head of the biceps tendon within the pulley: a 3 T MRI motion analysis.

INTRODUCTION: To evaluate the kinetic amplitude and direction of the long head of the biceps tendon (LHB) within the pulley and the proximal bicipital groove, we performed a 3T-magnetic resonance-throwing motion analysis. MATERIALS AND METHODS: This prospective study was performed on a 3T-MRI scanner. A T2-weighted-3D sequence in three specific positions of throwing motion of the dominant shoulder was performed under isometric 5 N loading conditions or without loading, respectively. Measurements were performed in high (140°) abduction/external rotation, medium (110°) abduction/external rotation and low (45°) adduction-flexion/internal rotation. Multiplanar rotational reconstructions along the LHB in the bicipital groove allowed for the localization of the LHB including the degree of motion in the three most proximal slices. RESULTS: 12 healthy volunteers (age 22­34 years) were enrolled. Adduction led to an anterior deviation of the LHB within the bicipital groove. Loading conditions in medium (110°) elevation/external rotation furthermore led to a significant anterior deviation of the LHB. Conclusion Our findings support the thesis that pulley lesions result from movements of the LHB especially in extreme positions during throwing/overhead activities. Load application in the medium (110°) elevation/external rotation position might enable a better evaluation of patients with dedicated pulley lesions. These results need further evaluation in larger study cohorts and in patients with dedicated rotator cuff lesions, which will be the focus of ongoing studies.

[Value of cross-sectional imaging in posttraumatic low grade infection]. / Wertigkeit der Schnittbildgebung bei posttraumatischem Low-Grade-Infekt.

Regarding imaging diagnostics in case of posttraumatic or postoperative chronic osteomyelitis, x-ray should be the first choice to obtain basic information of the affected bone. Because knowledge of the exact dimensions of the inflammatory changes is essential for adequate therapy planning, diagnostics via cross-sectional imaging is indicated in most cases. In order to adequately estimate the lesion's dimensions, magnetic resonance imaging (MRI) is the method of choice in these cases. Nuclear medicine examination techniques such as bone scintigraphy using specially marked granolocyte antibodies are alternatives to be considered for the evaluation of activated chronic osteomyelitis. CT exams are only rarely performed for the diagnosis of chronic osteomyelitis if a bone sequester can not be proven by either x-ray or MRI.

Detection of recurrent hernia and intraabdominal adhesions following incisional hernia repair: a functional cine MRI-study.

BACKGROUND: To non-invasively identify incisional hernia repair implanted synthetic meshes with MRI, and also focusing on the evaluation of postsurgical complications such as adhesions. METHODS: A total of 43 patients underwent either laparoscopic intraperitoneal onlay-mesh or open abdominal wall repair using preperitoneal layers. The patients were examined using a true-fast-imaging-with-steady-state-precession (trueFISP)-sequence in transverse/sagittal orientation with a section-by-section dynamic depiction of induced visceral slide. A 9-segment-abdominal-map was used to document the adhesion location/type. The MR-images were analysed regarding hernia relapse, layer-morphology, rectus-abdominis muscle-condition, and abdominal wall mobility. In 12 patients pre- and postsurgery-MRI was performed. RESULTS: Time range between surgery and examination was 6-36 months. In all laparoscopy-patients the meshes were identified. For open surgery the mesh was not visualized in 20, but was seen in 6 cases. A total of 11 cases showed a recurrent hernia. Seventy intraabdominal adhesions were detected. Fifteen patients had restricted mobility. 20 patients showed an rectus-abdominis-muscle-asymmetry. Comparing pre- and post-op-MRI, 6 out of 8 patients with open repair showed thick scar-plaques. Three patients with open repair had new adhesion-formations postoperatively. CONCLUSION: Functional cine MRI is suitable for follow-up studies in patients after hernia repair to detect and evaluate the implanted meshes. Typical complications like intestinal adhesions and abdominal wall dysmotility can be assessed as well.

[Sarcoidosis of lymph nodes in the submandibular compartment]. / Lymphknotensarkoidose der Submandibularisloge.

Sarcoidosis is a granulomatous systemic disease of unknown etiology. Besides the landmark pulmonary lesions, extrathoracic manifestations of the disease can also occur. We report the case of a 53-year-old woman with an obscure swelling of both submandibular compartments. The radiological and pathohistological evaluations confirmed the uncommon diagnosis of sarcoidosis of the submandibular compartment. The tumor in each compartment consisted of a huge lymph node conglomerate respectively displacing the submandibular gland. The major salivary glands and the thorax were not involved.

Stage-dependant management of septic arthritis of the shoulder in adults.

Diagnostic and therapeutic standards relating to septic conditions of the shoulder are rarely documented in the literature. For this study, patients suffering from septic shoulder arthritis were prospectively enrolled. Staging was based on the criteria of Gächter (Stutz et al., Knee Surg Sports Traumatol Arthrosc 8:270-274, 2000), and assessment of functional outcome was based on a self-assessed Constant score (Boehm et al., Unfallchirurg 107:397-402, 2004). Patients were separated into three groups according to the CEBI-classification reported by Pfeiffenberger and Meiss (Arch Orthop Trauma Surg 115:325-331, 1996). Forty-three patients were enrolled. Group I contained 21% of patients, while 23% were assigned to group II, and 56% to group III. Staphylococcus aureus was found in 71%. Eight patients were treated arthroscopically, and 35 received open surgery. None of the implants could be preserved. The mean self-assessed Constant score after 26 +/- 7 months was 74 +/- 9 points in group I, 63 +/- 14 points in group II, and 53 +/- 14 points in group III. Diagnostic work-up consisted of laboratory analysis including CRP and joint aspiration. Arthroscopic procedures can be effective when implemented early. With regard to implants and chronic symptoms, primary removal should be critically reconsidered.

Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice.

Intercellular channels of gap junctions are formed in vertebrates by the protein family of connexins and allow direct exchange of ions, metabolites and second messenger molecules between apposed cells (reviewed in [1-3]). In the mouse, connexin40 (Cx40) protein has been detected in endothelial cells of lung and heart and in certain heart muscle cells: atrial myocytes, cells of the atrial ventricular (AV) node and cells of the conductive myocardium, which conducts impulses from the AV node to ventricular myocyctes [3]. We have generated mice homozygous for targeted disruption of the Cx40 gene (Cx40-/-mice). The electrocardiograph (ECG) parameters of Cx40-/- mice were very prolonged compared to those of wild type (Cx40+/+) mice, indicating that Cx40-/- mice have lower atrial and ventricular conduction velocities. For 6 out of 31 Cx40-/- animals, different types of atrium-derived abnormalities in cardiac rhythm were recorded, whereas continuous sinus rhythm was observed for the 26 Cx40+/+ and 30 Cx40+/- mice tested. The expression levels of other connexins expressed in heart (Cx37, Cx43 and Cx45) were the same in Cx40-/- and Cx40+/+ mice. Our results demonstrate the function of Cx40 in the regulation and coordination of heart contraction and show that cardiac arrhythmogenesis can not only be caused by defects in the ion channels primarily involved in cellular excitation but also by defects in intercellular communication through gap junction channels. As the distribution of Cx40 protein is similar in mouse and human hearts, further functional analysis of Cx40 should yield relevant insights into arrhythmogenesis in human patients.

Apoptosis signaling in lymphocytes.

Lymphocyte apoptosis is essential for proper function of the immune system. Among other functions, it is responsible for the homeostasis of immune cells and plays a key role in the elimination of autoreactive lymphocytes. Recently, progress has been made in the identification of genes that regulate apoptosis. Studies characterizing the basic apoptosis signaling machinery have begun to reveal the molecular control of processes that modulate lymphocyte apoptosis.

The rad16 gene of Schizosaccharomyces pombe: a homolog of the RAD1 gene of Saccharomyces cerevisiae.

The rad10, rad16, rad20, and swi9 mutants of the fission yeast Schizosaccharomyces pombe, isolated by their radiation sensitivity or abnormal mating-type switching, have been shown previously to be allelic. We have cloned DNA correcting the UV sensitivity or mating-type switching phenotype of these mutants and shown that the correcting DNA is encompassed in a single open reading frame. The gene, which we will refer to as rad16, is approximately 3 kb in length, contains seven introns, and encodes a protein of 892 amino acids. It is not essential for viability of S. pombe. The predicted protein is the homolog of the Saccharomyces cerevisiae RAD1 protein, which is involved in an early step in excision-repair of UV damage from DNA. The approximately 30% sequence identity between the predicted proteins from the two yeasts is distributed throughout the protein. Two-hybrid experiments indicate a strong protein-protein interaction between the products of the rad16 and swi10 genes of S. pombe, which mirrors that reported for RAD1 and RAD10 in S. cerevisiae. We have identified the mutations in the four alleles of rad16. They mapped to the N-terminal (rad10), central (rad20), and C-terminal (rad16 and swi9) regions. The rad10 and rad20 mutations are in the splice donor sequences of introns 2 and 4, respectively. The plasmid correcting the UV sensitivity of the rad20 mutation was missing the sequence corresponding to the 335 N-terminal amino acids of the predicted protein. Neither smaller nor larger truncations were, however, able to correct its UV sensitivity.

Abnormal cardiac conduction and morphogenesis in connexin40 and connexin43 double-deficient mice.

Connexin40-deficient (Cx40(-/-)/Cx43(+/+)) and connexin43-heterozygous knockout mice (Cx40(+/+)/Cx43(+/-)) are viable but show cardiac conduction abnormalities. The ECGs of adult double heterozygous animals (Cx40(+/-)/Cx43(+/-)) suggest additive effects of Cx40 and Cx43 haploinsufficiency on ventricular, but not on atrial, conduction. We also observed additive effects of both connexins on cardiac morphogenesis. Approximately half of the Cx40(-/-)/Cx43(+/+) embryos died during the septation period, and an additional 16% died after birth. The majority of the latter mice had cardiac hypertrophy in conjunction with common atrioventricular junction or a ventricular septal defect. All Cx40(-/-)/Cx43(+/-) progeny exhibited cardiac malformations and died neonatally. The most frequent defect was common atrioventricular junction with abnormal atrioventricular connection, which was more severe than that seen in Cx40(-/-)/Cx43(+/+) mice. Furthermore, muscular ventricular septal defects, premature closure of the ductus arteriosus, and subcutaneous edema were noticed in these embryos. Cx40(+/-)/Cx43(-/-) embryos showed the same phenotype (ie, obstructed right ventricular outflow tract) as reported for Cx40(+/+)/Cx43(-/-) mice. These findings demonstrate that Cx43 haploinsufficiency aggravates the abnormalities observed in the Cx40(-/-) phenotype, whereas Cx40 haploinsufficiency does not worsen the Cx43(-/-) phenotype. We conclude that the gap-junctional proteins Cx40 and Cx43 contribute to morphogenesis of the heart in an isotype-specific manner.

Induction of apoptosis in 9-nitrocamptothecin-treated DU145 human prostate carcinoma cells correlates with de novo synthesis of CD95 and CD95 ligand and down-regulation of c-FLIP(short).

Stimulation of CD95 leads to oligomerization of this receptor and the recruitment of the Fas-associated death domain (FADD) and procaspase-8 to form the death-inducing signaling complex (DISC). Subsequent proteolytic activation of caspase-8 at the DISC leads to the activation of downstream caspases and execution of apoptosis. The anticancer drug 9-nitrocamptothecin (9NC) inhibits the nuclear enzyme topoisomerase I (Top1), an event followed by apoptosis of cancer cells. We investigated whether other mechanisms downstream of the DNA-Top1-9NC complexing step regulate the apoptotic ability of 9NC in DU145 cells. We demonstrate that induction of apoptosis in DU145 cells, upon exposure to 9NC, is associated with de novo expression of CD95 and CD95L, suggesting that 9NC-induced apoptosis is mediated by the CD95 system. In this line, we observed early activation of procaspase-3, -7, and -8, but not -1, -9, and -10. Moreover, 9NC treatment resulted in the dramatic down-regulation of c-FLIP(short) expression, but not that of c-FLIP(long) or FADD. Furthermore, incubation of DU145 cells with a neutralizing antibody (NOK-1) to CD95L or transient transfection of a c-FLIP(short) expression vector into DU145 cells partially abrogated 9NC-triggered apoptosis. We propose that 9NC triggers apoptosis by driving DU145 cells from a nonapoptotic status (c-FLIP(short)(high), CD95(low), CD95L(low)) toward a proapoptotic status (c-FLIP(short)(low), CD95(high), CD95L(high)). These findings indicate that in addition to a Top1-mediated effect, 9NC can additionally activate a CD95/CD95L-dependent apoptotic pathway.

Detection of blood aspiration in deadly head gunshots comparing postmortem computed tomography (PMCT) and autopsy.

BACKGROUND: The aim of our study was to analyze the reliability of postmortem computed tomography (PMCT) versus autopsy in detecting signs of blood aspiration in a distinct group of patients following deadly head, mouth or floor of mouth gunshot injuries. METHODS: In this study, in 41 cases PMCT was compared to autopsy reports, the gold standard of postmortem exams, regarding detection of blood aspiration. PMCT was evaluated for the presence and level of typical signs of blood aspiration in the major airways and lung using a semi-quantitative scale ranging from level 0 (no aspiration) to 3 (significant aspiration) also taking density values of the described potential aspiratory changes into account. RESULTS: Overall, in 29 (70.7%) of 41 enrolled cases PMCT and autopsy revealed the same level of aspiration. A difference of one level between PMCT and autopsy resulted for 5 (12.2%) of the remaining 12 cases. More than one level difference between both methods resulted for 7 cases (17.2%). Autopsy described no signs of aspiration in 10 cases, compared to 31 cases with reported blood aspiration. In contrast, PMCT revealed no signs of blood aspiration in 15 cases whereas 26 cases were rated as positive for signs of aspiration in the major airways. In 18 of these 26 cases considered positive for blood aspiration by autopsy and PMCT, clear signs of aspiration signs were also described bilaterally by both methods. CONCLUSIONS: The presented study provides evidence for the assumption that PMCT seems to be helpful in the detection of blood aspiration in cases of deadly head gunshots. In conclusion, it seems reasonable to suggest performing PMCT additionally to traditional postmortem exams in cases of suspected aspiration to rule out false-negative cases and to possibly allow for a more detailed and rather evidence based examination reconnoitering the cause of death. However, the adequate use of PMCT in this context needs further evaluation and the definition of an objective scale for aspiration detection on PMCT needs to be established in future studies.

Substrain and light regime effects on integrated anxiety-related behavioral z-scores in male C57BL/6 mice-Hypomagnesaemia has only a small effect on avoidance behavior.

Magnesium (Mg) has been described to possess an anxiolytic function, but a number of studies present inconsistent results on this matter. In this study the effect of Mg deficiency on anxiety-related behavior, brain and blood plasma Mg in young adult male C57BL/6JOlaHsd and C57BL/6NCrl mice was studied. The animals were put on a control or Mg deficient diet from day 0 and significant hypomagnesaemia was evident from day 12 onwards in the test animals. Housing and test conditions were under either conventional light regime (white light behavioral test conditions) or reverse light regime (red light behavioral test conditions). The animals were tested in three tests for unconditioned anxiety: the modified Hole Board (day 14), the light-dark test (day 21) and the elevated plus maze (day 28). Overall integrated behavioral z-scores were calculated over these three behavioral tests. Mg showed a structure dependent distribution at the level of the brain, that differed between C57BL/6 substrain and light regime (conventional versus reverse), respectively. Likewise, total brain Mg did differ between substrain and light regime, but was not affected by the diet. Animals on the Mg deficient diet housed under conventional light regime had a higher final (day 28) blood plasma corticosterone level as compared to controls. Animals housed under reverse light regime exhibited no diet effect of plasma corticosterone levels. The significant hypomagnesaemia at blood plasma level resulted in an effect of Mg deficiency on avoidance, but not overall anxiety-related behavior. Significant differences regarding avoidance behavior were found between the two substrains and light regimes, respectively.

Cooperative activity between HER oncogenes and the tumor suppressor IRF-1 results in apoptosis.

The tumor suppressor transcription factor IRF-1 inhibits cell growth. In this report we show that IRF-1 also induces apoptosis of highly transformed and tumorigenic cell lines. This activity of IRF-1 is demonstrated with cell lines expressing HER oncogenes and an activatable IRF-1 fusion protein. Growth of cell lines expressing inactive HER1 is inhibited on IRF-1 activation. In contrast, the same cells are killed by apoptosis when HER1 and IRF-1 are activated simultaneously. We identified promoters stimulated synergistically by IRF-1 and by activated HER1. To determine the signals causing transcriptional synergism and/or apoptosis we tried to modulate these effects by various dominant negative acting proteins. Dominant negative STAT5alpha abolished both induction of apoptosis and transcriptional synergy of IRF-1 and HER. Thus, these results provide new insights into the mechanism of oncogene-dependent apoptosis induced by the activation of a tumor suppressor.

IRF-1 induced cell growth inhibition and interferon induction requires the activity of the protein kinase PKR.

Expression of the tumor suppressor IRF-1 results in the inhibition of cell growth and transcriptional activation of the IFN-beta gene. IFN production is not responsible for the IRF-1 mediated cell growth inhibition. It is shown here that activation of the IRF-1 causes induction of PKR expression. PKR is a serine/threonine kinase with tumor suppressor activity. IRF-1 mediated cell growth inhibition and IFN induction correlates with PKR expression. A catalytically inactive dominant negative PKR mutant abolishes both activities of IRF-1. These data demonstrate that the tumor suppressor activity of IRF-1 is mediated, at least in part, by PKR.