Pathological Role for Exocytotic Glutamate Release from Astrocytes in Hepatic Encephalopathy

Liver failure can lead to generalized hyperammonemia, which is thought to be the underlying cause of hepatic encephalopathy. This neuropsychiatric syndrome is accompanied by functional changes of astrocytes. These glial cells enter ammonia-induced self-amplifying cycle characterized by brain oedema, oxidative and osmotic stress that causes modification of proteins and RNA. Consequently, protein expression and function are affected, including that of glutamine synthetase and plasmalemmal glutamate transporters, leading to glutamate excitotoxicity; Ca²⁺-dependent exocytotic glutamate release from astrocytes contributes to this extracellular glutamate overload.     

Contribution of forensic anthropology to identification process in Croatia: examples of victims recovered in wells

Aim

To describe the contribution of forensic anthropology to the recovery, analysis, and identification of victims from the 1991-1995 war in Croatia recovered in wells.

Methods

From 1996 to the present, human remains of a total of 61 individuals have been recovered from 13 wells. Six wells contained the remains of a single individual, one well contained the remains of 2 individuals, and 6 wells contained the remains 3 or more individuals. The majority of wells, containing 90.2% (55/61) of recovered individuals, were located within a 4 km radius of the Croatian-Serbian border.

Results

Forensic anthropologists re-individualized 26/61 (42.6%) individuals out of skeletonized and commingled remains, provided basic biological data on sex, age-at-death, and stature in all identifications (n = 37), as well as established positive identification by recognizing unique skeletal features (antemortem fractures and skeletal evidence of antemortem surgical interventions) in 3/37 (8.1%) cases. Trauma analyses carried out by forensic anthropologists contributed to the determination of the cause of death in 38/61 (62.3%) individuals and to the probable cause of death in an additional 18/61 (29.5%) individuals. The most frequent (27/38, 71.0%) type of trauma causing death in individuals recovered from wells was a single gunshot wound.

Conclusion

Forensic anthropologists, collaborating closely with forensic pathologists, forensic odontologists, forensic radiologists, criminologists, and molecular biologists contributed significantly to trauma analysis and identification of war victims recovered from wells.To address the need for identification of a large number of war victims in the 1991-1995 war in Croatia (1-8), in 1991 the Croatian Government formed a multidisciplinary team of forensic experts with a purpose of recovering, analyzing, and identifying human remains from individual and mass graves. This report describes the contribution of forensic anthropologists to this endeavor, specifically to the recovery, analysis, and identification of 61 individuals recovered from 13 wells in Croatia after the 1991-1995 war. The recovery and analysis of these individuals was, for a number of reasons, considerably more complicated than the recovery and analysis of individuals from other types of mass graves and individual graves (1).For obvious reasons, the recovery of human remains deposited in wells was more hazardous than the recovery of remains from other types of settings. Standard risks associated with this type of work are difficult access to the grave sites through mine fields, possible explosive devices hidden among the remains, and poorly preserved human remains. Besides this, recovery from wells was complicated by varying depth of the wells, problems pertaining to the draining off the wells, and – in the case of more dilapidated wells – the risk of collapse of the well walls. Trauma analyses and identification of the recovered individuals was hampered by problems such as poor preservation and commingling of the remains which were significantly more present in wells than in other types of settings (1).The multidisciplinary team assembled by the Croatian government to recover and identify missing individuals included forensic pathologists, forensic anthropologists, forensic odontologists, forensic radiologists, criminologists, and molecular biologists. Forensic anthropologists contributed to this team effort by: 1) helping in locating and recovering human remains; 2) separating and re-individualizing commingled remains; 3) interpreting skeletal evidence of trauma – identifying the presence of trauma, differentiating between antemortem, postmortem, and perimortem trauma, as well as establishing the sequence of perimortem traumas, when possible; and 4) adopting an osteo-biographical approach in order to supply not only basic data on the age-at-death, sex, and stature, but also on other biological characteristics potentially useful in the identification process. To facilitate this, a joint US-Croatian forensic anthropology project was developed. In this project, forensic anthropologists from the Croatian Academy of Sciences and Arts and forensic specialists from the Department of Forensic Medicine at the School of Medicine, University of Zagreb, together with forensic anthropologists from the Smithsonian Institution, Washington DC, USA and the University of Tennessee in Knoxville developed a forensic anthropology database. Data on sex, age-at-death, stature, cranial and postcranial metric characteristics, and osteological and dental features were collected, including the evidence on pathology, ante-mortem fractures, disease, and surgical interventions, as well as perimortem trauma and possible cause of death. The purpose of this database was 3-fold: 1) to identify a basic and standard set of measurements, observations, and definitions to ensure that data are comparable; 2) to store the data in a computer so that particular subsets can be quickly accessed, analyzed, and compared; and 3) to provide up-to-date discriminant formulae for determining sex, stature, and other traits useful for comparative research and forensic analysis. The data gathered so far have already been proved useful for calculating discriminant functions for determining sex from fragmentary and complete Croatian femora (3), estimating male stature from the maximum lengths of the humerus, femur, and tibia (9), as well as determining craniometric relationships between Americans (Caucasians), Croatians, and Bosnians (10).     

Prevalence of hair shedding among women

Hair shedding in female patients is a frequent complaint in dermatological, endocrinological, and gynecological consults. Previously, the Sinclair Hair Shedding Scale was developed to assess normal versus excessive hair shedding in female pattern hair loss (FPHL) subjects. However, the prevalence of hair shedding in females not suffering from FPHL is unknown. To gain better understanding of hair shedding in the general population, we recruited 300 subjects visiting a public hospital for conditions other than alopecia. Of the 300 subjects recruited, 263 did not suffer from FPHL. Among those subjects, approximately 40% reported experiencing excessive hair shedding (as defined by the Sinclair Hair Shedding Scale) on hair washing days. In comparison, in our subject population, approximately 60% of subjects with FPHL reported excessive hair shedding on hair washing days. To best of our knowledge, this is the first study to quantify the prevalence of hair shedding in women. While, no treatment currently exists for this condition, we hope that this study would encourage physicians and researchers to address this frequent concern.     

Developmental delay associated with normal thyroidal function and long-term amiodarone therapy during fetal and neonatal life

We reported a case of a child with neurodevelopment delay induced by long-term amiodarone exposure due to a treatment of fetal supraventricular tachycardia (FSVT), subtype permanent junctional reciprocating tachycardia (PJRT) with the normal thyroidal function. Refractory persistent FSVT was treated intrautero with digoxin (0.5 mg QD) until delivery and amiodarone (100 mg QD) from 26 to 35 weeks of gestation. A baby weighing 3550 g with normal acid-base status was delivered at 38 weeks of gestation. The PJRT recurred 28 hours after delivery and reverted to sinus rhythm with amiodarone and propranolol for another 24 months. The neurological disturbances were manifested at the age of 12 months, when hypotonia and delayed motor milestones were recognised. At the age of 18 months, the child had mildly neurological development delay with hypotonia, ataxia and foot deformities. At the age of 24 months, motor milestones were mildly delayed with the usage of a few words without the ability to connect them into the sentence. The developmental quotient (DQ) was 68. Electroencephalogram and magnetic resonance imaging of the central nervous system were all normal. At the age of 30 months, motor milestones were still delayed together with speech development and language delay, only some words were used, not distinctly, DQ was 78. Thyroid function was normal on each examination. All blood and urine analyses were in normal ranges. Chromosome analysis did not show any abnormalities. Since we excluded all possible reasons, we could only bring an indirect link between the long-term amiodarone exposure during fetal and postnatal life and neurodevelopment delay.     

Arterial ischemic stroke in a child with beta-thalassemia trait and methylentetrahydrofolate reductase mutation

Genetic and acquired disorders that foster a procoagulable state represent risk factors for stroke in childhood. Although an increased incidence of thromboembolic complications has been reported in patients with thalassemia, severe cerebral thromboembolism has rarely been observed in patients with beta-thalassemia minor. This article describes a case study of a 1-year-old boy who presented with left-sided hemiparesis, seizures, microcytic anemia, and recent infection with reactive thrombocytosis. Ischemic infarction in the territory of the right middle cerebral artery was confirmed by magnetic resonance imaging and magnetic resonance angiography. Genetic tests showed that the patient was heterozygous for the beta(degrees) -thalassemia IVS-I-1 mutation and homozygous for the methylentetrahydrofolate reductase C677T mutation. Based on these findings, it was concluded that the synergistic effects of multiple, genetic, and acquired prothrombotic risk factors brought about the hypercoagulable state that resulted in overt stroke in a thalassemic patient in early childhood.