The PERFORM-P (Principles of Evidence-based Reporting in FORensic Medicine-Pathology version).

INTRODUCTION: Most findings of forensic pathology examinations are presented as written reports. There are currently no internationally accepted recommendations for writing forensic pathology reports. Existing recommendations are also varied and reflect the differences in the scope and role of forensic medical services and local settings in which they are to be implemented. The legal fact-finder thus faces wide variation in the quality of forensic pathology reports, which poses a threat to the reliability of legal decision-making. To address this issue, the development of the "PERFORM-P (Principles of Evidence-based Reporting in FORensic Medicine-Pathology version)" was undertaken. The goal of the PERFORM-P is to provide common practice recommendations adaptable to local requirements to promote evidence-based practice (EBP) in forensic pathology. METHODS: An international consensus study was conducted in three phases by (1) developing a long-list of items to be considered in the reporting recommendations, (2) conducting a Delphi process (an iterative survey method to transform individual opinions into group consensus) with international forensic pathologists, and (3) designing the PERFORM-P prototype and its accompanying manual. RESULTS: With assistance from 106 forensic pathologists/forensic medical practitioners from 41 countries, the PERFORM-P was developed. The PERFORM-P consists of a list of 61 items to be included in a forensic pathology report, which is accompanied by its Explanation and Elaboration (E&E) document. DISCUSSION: To prepare forensic pathology (postmortem) reports that incorporate principles of evidence-based practice, internationally accepted recommendations might be helpful. The PERFORM-P identifies recommendations for necessary elements to include in a forensic pathology report. PERFORM-P can be applied to a wide range of matters requiring forensic pathological analysis, acceptable to forensic pathologists from a representative selection of jurisdictions and medico-legal systems.

Post-mortem computed tomography in forensic investigations of lethal gunshot incidents: is there an added value?

The aim of this study is to assess the added value of post-mortem computed tomography (PMCT) in fatal shooting incidents compared with autopsy findings. For this study, the analysis was restricted to the following four features: location of the entrance and exit wounds, internal injuries, location of projectiles or metal fragments and course of the trajectories. These features were selected because they provide essential information on the cause and manner of death. All data were retrospectively collected from medical forensic examinations of fatal shooting incidents in the Netherlands that occurred in 2010-2014. Twenty-one fatal shooting victims were included in this study, with a total of 100 trajectories. For all 100 trajectories, the forensic radiologist and pathologist came to a consensus on which examination had the highest diagnostic value for each of the four features. PMCT provides superior information on the presence of metal fragments, internal injuries and the course of trajectories. PMCT provides limited information on the discrimination of entrance and exit wounds. In conclusion, PMCT provides additional relevant information in over 60% of forensic medical examinations of deceased victims of shooting incidents. We therefore recommend adding PMCT as a standard examination in these cases.

Evaluation of a novel dye for near-infrared fluorescence delineation of the ureters during laparoscopy.

BACKGROUND: Iatrogenic ureteric injury remains a risk in laparoscopic pelvic procedures. Near-infrared fluorescence (NIRF) imaging is a promising new technique for enhanced intraoperative visualization of anatomical structures that could improve the safety of laparoscopic surgery. A new dye, IRDye® 800-BK, has been developed for intraoperative visualization of the ureters using NIRF. The present study was a first evaluation of the performance of IRDye® 800-BK for ureteric imaging during NIRF laparoscopy. METHODS: This study consisted of three parts: real-time in vivo NIRF imaging using IRDye® 800-BK in pigs during laparoscopic surgery, ex vivo NIRF imaging of freshly explanted pig ureters and ex vivo NIRF imaging of explanted human ureters. RESULTS: In all animals, both left and right ureters were visualized throughout the laparoscopic procedure for 120 min, with the best results at a dose of 0·15 mg dye per kg bodyweight. NIRF imaging was successful in all human and porcine ureters studied, with a range of dye concentrations. CONCLUSION: NIRF imaging of the ureters using IRDye® 800-BK was used successfully both in vivo in a porcine model, and ex vivo in porcine and human ureters.

Toxicological results in a fatal and two non-fatal cases of scopolamine-facilitated robberies.

The use of scopolamine as an incapacitating drug, in sexual crimes and robberies, has been known for many decades. However, blood concentrations and doses of scopolamine in those cases are largely unknown. Here we present the toxicological results of one fatal and two non-fatal cases in a series of scopolamine-facilitated robberies. In the fatal case, the concentration of scopolamine in heart blood was 0.30mg/L, about 3000 times higher than the average therapeutic level of 0.0001mg/L (for one dermal patch). In femoral blood, the concentration of scopolamine was much lower (0.0048mg/L), but still 50 times higher than therapeutic levels. The scopolamine concentration in the stomach was very high (20mg/kg) as compared to the heart blood and femoral blood, which explains the very high concentration in heart blood by postmortem leakage from the stomach. In the non-fatal case, the scopolamine concentration in serum, obtained 23h after the incident, was 0.00035mg/L. The estimated concentration of scopolamine at the time of the incident is 0.0035mg/L. In the other non-fatal case, scopolamine was detected in urine and in hair.

Dying in the arms of Dutch governmental authorities.

Thorough investigation of deaths related to police actions or of persons placed under the 'care' of governmental authorities is anchored in the legal systems of every democratic system. The quality of this investigation should be guarded by an adequate set of control measures. Recently the Dutch Ombudsman published a report about this issue In the Netherlands no central registry of these deaths exists. The estimates based on the available data number some 400-500 deaths in custody in the past 10 years in the Netherlands of which only in 193 cases a legal postmortem was performed. We present an overview of these cases and discuss the present Dutch practice in the perspective of national and international legislation.

Multicystic encephalomalacia as an end-stage finding in abusive head trauma.

Abusive head trauma (AHT) is one of the most severe forms of physical child abuse. If a child initially survives severe AHT the neurological outcome can be poor. In recent years several children were seen who developed multicystic encephalomalacia (MCE) after documented severe AHT. A search of the Netherlands Forensic Institute database in The Hague was performed. Inclusion criteria were cases of AHT between 1999 and 2010 where the child was under the age of 1 year old at the time of trauma. Trauma mechanism and radiological information were collected. Five children, three boys and two girls (mean age 57 days, range 8-142 days) who developed cystic encephalomalacia after inflicted traumatic brain injury were included. Survival ranged from 27 to 993 days. In all cases judicial autopsy was performed. All cases came before court and in each case child abuse was considered to be proven. In two cases the perpetrator confessed, during police interrogation, to shaking of the child only. Although a known serious outcome, this is one of the few reports on MCE as a result of AHT. In all cases the diagnosis was confirmed at autopsy.

Limited role for C. pneumoniae, CMV and HSV-1 in cerebral large and small vessel atherosclerosis.

AIMS: To explore whether Chlamydia pneumoniae, Cytomegalovirus and Herpes Simplex Virus type 1 could be detected in large and small cerebral arteries, as well as in an area of brain parenchyma where white matter lesions (leukoaraiosis) can be found, in patients with clinically unmanifested cerebrovascular atherosclerosis. Methods and results( Arterial specimens from the basilar artery and middle cerebral artery, and brain samples from the basal ganglia and periventricular white matter were obtained. Neuropathological changes were assessed in Haematoxylin-Eosin stained sections. Polymerase chain reaction (PCR) was performed on paraffin embedded sections. Subsequently, we performed immunohistochemical staining on samples, which were found positive in PCR. We failed to detect C. pneumoniae, CMV, or HSV-1, in any of the cerebral large vessels. In the brain tissue, we found only one case positive for CMV, and one for C. pneumoniae. Conclusions (our findings suggest a limited role for C. pneumoniae, CMV and HSV-1 in cerebral large and small vessel atherosclerosis.

Cerebral arterial air embolism in a child after intraosseous infusion.

Cerebral arterial air embolism (CAAE) has been reported as a rare complication of medical intervention. There has been one reported case of CAAE after the use of an intraosseous infusion (IO) system. We report on a case of CAAE after tibial IO infusion in a 7-month-old girl during resuscitation.

[Diagnostic image (166). Sudden death in a young woman. Cyst of the pineal gland with a prominent cerebellar tonsillar herniation]. / Diagnose in beeld (166). Plotse dood bij een jonge vrouw. Gliale cyste van de glandula pinealis met inklemming van de cerebellaire tonsillen.

A 27 year-old woman died unexpectedly due to a cyst of the pineal gland with a prominent cerebellar tonsillar herniation.

Myopathological features in skeletal muscle of patients with chronic obstructive pulmonary disease.

Despite the fact that muscle weakness is a major problem in chronic obstructive pulmonary disease (COPD), detailed information on myopathological changes at the microscopic level in these patients is scarce, if indeed available at all. Vastus lateralis biopsies of 15 COPD weight-stable patients (body mass index (BMI) 23.9+/-1.0 kg x m(-2); fat-free mass index (FFMI) 17.2+/-1.7 kg x m(-2)) and 16 healthy age-matched controls (BMI 26.3+/-0.8 kg x m(-2); FFMI 19.6+/-2.2 kg x m(-2)) were evaluated. Histochemistry was used to evaluate myopathological features. Immunohistochemistry was used for the detection of macrophages and leukocytes, and active caspase 3 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) as markers of apoptosis. Fatty cell replacement and fibrosis were observed in both groups, the latter being slightly, but significantly, more pronounced in COPD. No differences between COPD and controls were found with respect to central nuclei, necrosis, regeneration, or fibre splitting. Signs of mitochondrial abnormalities were absent and normal numbers of inflammatory cells were found. Active caspase 3 positive myocytes were not observed and no difference was found in the number of TUNEL-positive myonuclei between controls and COPD patients (1.1% versus 1.0%, respectively). The cross-sectional area of type-IIX muscle fibres was smaller in COPD than in controls (2,566 versus 4,248 microm2). Except for the I to IIX shift in fibre types, the selective type-IIX atrophy and a slight accompanying increase in fibrosis and fat cell replacement in chronic obstructive pulmonary disease relative to age-matched controls, no other morphological abnormalities were observed in the muscle biopsies of chronic obstructive pulmonary disease patients. Also, in this group of clinically and weight stable chronic obstructive pulmonary disease patients, apoptosis appeared not to be involved in muscle pathology.

Proliferation and aneusomy predict survival of young patients with astrocytoma grade II.

The clinical course of astrocytoma grade II (AII) is highly variable and not reflected by histological characteristics. As one of the best prognostic factors, higher age identifies rapid progressive A II. For patients over 35 years of age, an aggressive treatment is normally propagated. For patients under 35 years, there is no clear guidance for treatment choices, and therefore also the necessity of histopathological diagnosis is often questioned. We studied the additional prognostic value of the proliferation index and the detection of genetic aberrations for patients with A II. The tumour samples were obtained by stereotactic biopsy or tumour resection and divided into two age groups, that is 18-34 years (n=19) and > or =35 years (n=28). Factors tested included the proliferation (Ki-67) index, and numerical aberrations for chromosomes 1, 7, and 10, as detected by in situ hybridisation (ISH). The results show that age is a prognostic indicator when studied in the total patient group, with patients above 35 years showing a relatively poor prognosis. Increased proliferation index in the presence of aneusomy appears to identify a subgroup of patients with poor prognosis more accurately than predicted by proliferation index alone. We conclude that histologically classified cases of A II comprise a heterogeneous group of tumours with different biological and genetic constitution, which exhibit a highly variable clinical course. Immunostaining for Ki-67 in combination with the detection of aneusomy by ISH allows the identification of a subgroup of patients with rapidly progressive A II. This is an extra argument not to defer stereotactic biopsy in young patients with radiological suspicion of A II.

[Two patients with isolated vasculitis of the central nervous system]. / Twee patiënten met geïsoleerde vasculitis van het centrale zenuwstelsel.

Over the course of time, a 43-year-old woman and a 39-year-old man developed visual, sensory, motor, cerebellar and cognitive disturbances. Initially these occurred episodically, but later became continuous. Isolated vasculitis of the central nervous system was only diagnosed after brain biopsies were taken, upon which treatment with prednisone and cyclophosphamide was instituted. In both patients the symptoms persisted for 23 and 19 months, respectively, after treatment was initiated, but no new symptoms developed. The woman did, however, develop pancytopenia as a result of the cyclophosphamide treatment. Non-infectious vasculitis of the small veins and arterioles of the brain is lethal if left untreated. Leptomeningeal and cortical biopsy is essential in establishing the diagnosis in order to rule out other causative diseases. Combination therapy consisting of prednisone and cyclophosphamide for at least one year is recommended. The efficacy of this treatment is unknown due to the rarity of this disease.

Differentiation between reactive gliosis and diffuse astrocytoma by in situ hybridization.

The authors examined the use of chromosomal analysis by in situ hybridization to differentiate between nonneoplastic reactive gliosis and astrocytomas in cases in which routine histology was inconclusive. Numerical chromosomal aberrations were found in 80% of low-grade astrocytoma specimens and in none of the reactive gliosis specimens. Aneusomic tumor cells were detected in four of 13 stereotactic samples with an initially inconclusive tissue diagnosis, three of which were later diagnosed as astrocytoma. The in situ hybridization procedure may have additional value in the differential diagnosis of reactive gliosis versus low-grade astrocytoma.

Role of xanthine oxidase in passive Heymann nephritis in rats.

Passive Heymann nephritis (PHN) in rats is a model of human membranous nephropathy characterized by formation of subepithelial immune deposits in the glomerular capillary wall and complement activation. Oxygen radicals have been implicated in the subsequent glomerular damage which leads to proteinuria. This study examines the involvement of xanthine oxidase in this process. Xanthine oxidase activity was increased nearly twofold in glomeruli isolated 1 and 12 d after induction of PHN, and this was associated with increased glomerular superoxide anion generation. Analysis of glomerular samples by Northern and Western blotting revealed no quantitative changes in xanthine oxidoreductase expression in PHN, suggesting conversion of xanthine dehydrogenase to the oxidase form as the cause of increased activity. Treatment of rats with tungsten, an inhibitor of xanthine oxidase, before induction of PHN resulted in a marked decrease in glomerular xanthine oxidase activity and superoxide anion generation, and decreased proteinuria by 80% (day 12: 423+/-245 mg/d in PHN versus 78+/-53 mg/d in tungsten-treated PHN animals, P < 0.01). These findings point to a pivotal role of xanthine oxidase in the pathophysiology of PHN and could be of importance in the therapy of human membranous nephropathy.

Antioxidant-oxidant balance in the glomerulus and proximal tubule of the rat kidney.

1. Antioxidant and oxidative enzymes were examined in renal glomeruli and proximal tubules of healthy young rats (10-12 weeks old), and results were related to the superoxide anion generation of these tissues. 2. Activities of superoxide dismutases, catalase, and glutathione peroxidase were 3- to 6-fold higher in proximal tubules than in glomeruli. Similarly, enzyme levels and mRNA levels of superoxide dismutases and catalase were significantly higher in proximal tubules. 3. NADH- and NADPH-dependent oxidase activity and xanthine oxidase activity were not different in glomeruli and proximal tubules. 4. Measurements with lucigenin-enhanced chemiluminescence in vital tissues indicated 10-fold higher rates of superoxide anion in glomeruli than in tubules. 5. Compared with the young rats, tubules of 8-month-old rats had significantly higher superoxide anion rates and lower superoxide dismutase activity, whereas NADH- and NADPH-dependent oxidase activities were unchanged. 6. We conclude that considerable differences in the antioxidant-oxidant balance exist between the glomerulus and proximal tubule. Results from experiments using chemiluminescence in vital tissues suggest that changes in the antioxidant-oxidant balance have an effect on oxygen radical levels. The relevance of the observed differences to glomerular and tubulo-interstitial disease remains to be determined, but a greater susceptibility of the glomerulus to oxidant stress might be anticipated.

Reactive oxygen species and antioxidant defense in puromycin aminonucleoside glomerulopathy.

Results from several radical scavenger studies indirectly suggested an involvement of reactive oxygen species in the pathogenesis of puromycin aminonucleoside glomerulopathy. In this study, generation of reactive oxygen species was examined directly in glomeruli isolated from rats in the acute phase of puromycin aminonucleoside nephrosis and related to the changes in the glomerular antioxidant defense. Five and nine days after puromycin aminonucleoside injection, gross proteinuria, reduced creatinine clearances, and typical changes of glomerular morphology were present. Levels of reactive oxygen species were increased eightfold in glomeruli isolated 15 min after puromycin aminonucleoside injection, returned to baseline levels on days 1 and 5 after injection, and rose again to 14-fold on day 9 after injection, as determined by chemiluminescence with luminol. Further analysis of increased glomerular radical generation, using the chemiluminescence enhancer lucigenin and different radical scavengers, suggested a predominant involvement of hydroxyl radical and hydrogen peroxide in the initial increase in reactive oxygen species 15 min after puromycin aminonucleoside. Nine days after induction of nephrosis, primarily superoxide anion and hydroxyl radical were found to contribute to increased reactive oxygen species. Despite oxidative stress, antioxidant enzymes were not induced in the course of nephrosis. On the contrary, catalase and glutathione peroxidase activities declined 9 d after puromycin aminonucleoside injection. The results indicate that a transient increase in glomerular reactive oxygen species is sufficient to induce the oxidative glomerular injury observed in this model and that the glomerulus may not necessarily respond to oxidative stress with an induction of antioxidant enzymes.

[Rupture of PTCA balloons--an in vitro study]. / Ruptur von PTCA-Ballons--eine In-vitro-Untersuchung.

A large number of PTCA balloon catheters from different manufacturers were examined following their use. Several of these balloons had been previously used for PTCA for the mere purpose of guide wire support. Each balloon was evaluated starting at 8 atm. The pressure was increased in steps of 1 atm until rupture. This stepwise increase of pressure was documented at each level in a short cine film. During dilatations, balloons were in room air until rupture. None of the balloons ruptured before the rated burst pressure. A few of the balloons tolerated pressures of approximately 27 atm. With increasing pressure the shape of the balloons became distorted. Most assumed a banana shape. Most of the balloons ruptured after developing a small hole. Increasing pressure produced increasing diameter, and, generally, we found a linear increase. Most balloons increased by > 15% in diameter over the nominated diameter before rupture. The burst pressure in all balloons was not influenced by the prior mode of dilation, duration of dilation, maximum pressure applied, or length of the balloon. Balloons with smaller diameter ruptured later than compared to those with larger diameters. Our findings demonstrated that all of the balloons tolerated the manufacturers' recommended inflation pressure supporting the safety in their use.

Liposarcoma with unusual neurological manifestations.

Central nervous system involvement in liposarcoma is rare, the only symptom reported in the literature being local compression of the spinal cord. An exceptional case with peripheral nerve involvement due to local recurrence, in addition to spinal cord compression and cavernous sinus syndrome due to metastases is reported.

Intravascular lymphomatosis of the CNS: clinicopathologic study and search for expression of oncoproteins and Epstein-Barr virus.

Five cases of intravascular lymphomatosis (IVL) are reported. Diffuse or focal cerebral signs suggestive of vascular disease occurred in four cases, but case 5 presented with symptoms similar to Creutzfeld-Jakob disease. Clinical course ranged from two to eight months and diagnosis was made in all cases by autopsy. Neoplastic lymphoid cells mainly lodged in lumina of small vessels in many organs, but infarction was confined to the CNS. Some extravascular tumor cells were regularly seen. All cases corresponded to high-grade Non-Hodgkin lymphomas of B-cell type and displayed high proliferation indices. Different from findings in primary cerebral and nodal lymphomas, neither p53 nor bcl-2 oncoproteins were detectable. Absence of EBV genome and EBV latent membrane protein from IVL was demonstrated for the first time.