Brief review: History, concept and controversies in the neurological determination of death

PURPOSE: Despite general worldwide acceptance of the concept of neurological determination of death (NDD), inconsistencies in clinical criteria and ancillary testing requirements remain. Numerous guidelines for NDD may be applied in clinical practice by a variety of medical practitioners, but the scientific rationale for specific guideline recommendations often remains unclear. This review examines the evolution of NDD, and seeks to provide scientific validation for existing NDD criteria. SOURCE: English language peer-reviewed medical journals and established contemporary medical texts. PRINCIPAL FINDINGS: Currently published guidelines appear to have evolved from the work of the ad hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. The Conference of the Royal Colleges and Faculties of the United Kingdom refined the criteria and subsequently adopted the principal of brainstem death. While the fundamentals of NDD guidelines are remarkably consistent worldwide, specific criteria and requirements are often inconsistent. CONCLUSION: Numerous controversies regarding NDD continue to exist, necessitating further scientific clarification of these issues. More recently published guidelines representing the collective opinion of world experts in NDD based upon best current scientific evidence are available in current medical journals.     

25-Hydroxyvitamin D3 metabolism in a human leukemia cell line

Summary 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D₃ (25(OH)D₃) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD₃ to 1,25(OH)₂D₃ by HL-60, we exposed HL-60 cells to 25OHD₃ and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)₂D₃. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD₃ (19-Nor-25OHD₃). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD₃ also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)₂D₃ and similar to that of 25OHD₃. In agreement with the effect upon cell maturation, 19-Nor-25OHD₃ displaces³H-1,25(OH)₂D₃ from its HL-60 receptor with an efficiency comparable to 25OHD₃. Hence, HL-60 cells convert 25OHD₃ to 19-Nor-25OHD₃, and 19-Nor-25OHD₃ induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD₃.     

Use of abdominal ultrasonography to assess pediatric splenic trauma. Potential pitfalls in the diagnosis.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of abdominal ultrasonography (US) for screening and grading pediatric splenic injury. SUMMARY BACKGROUND DATA: The use of abdominal US has increased rapidly as a method of evaluating organ damage after blunt abdominal trauma. Despite US's increasing use, little is known about its accuracy in children with splenic injury. METHODS: Children (N = 32) suffering blunt abdominal trauma who were diagnosed with splenic injury by computerized tomography (CT) scan prospectively were enlisted in this study. Degree of splenic injury was evaluated by both CT and US. The ultrasounds were evaluated by an initial reading as well as by a radiologist who was blinded as to the results of the CT. RESULTS: Twelve (38%) of the 32 splenic injuries found on CT were missed completely on the initial reading of the US. When the ultrasounds were graded in a blinded fashion, 10 (31%) of the splenic lacerations were missed and 17 (53%) were downgraded. Seven (22%) of the 32 splenic fractures were not associated with any free intraperitoneal fluid on the CT scan. CONCLUSIONS: This study has shown that US has a low level of sensitivity (62% to 78%) in detecting splenic injury and downgrades the degree of injury in the majority of cases. Reliance on free intraperitoneal fluid may be inaccurate because not all patients with splenic injury have free intra-abdominal fluid. Based on these findings, US may be of limited use in the initial assessment, management, and follow-up of pediatric splenic trauma.     

Congenital bifid sternum. Report of an unusual case

This article presents the case of a child with an unusual type of cleft sternum characterized by fusion superiorly between the clavicles and inferiorly at the xiphoid with wide intervening separation. The defect was successfully corrected at age 17 months by surgical closure of the cleft primarily, which had not been achieved previously in a patient at this late age.     

MR imaging in patients with intracranial aneurysm clips

Four patients with intracranial aneurysm clips made from a variety of alloys were studied without incidence by MR imaging at field strengths ranging from 0.35 to 0.6 T. Knowledge of the type of alloy used in the manufacturing of an aneurysm clip is important in determining whether the clip will or will not deflect in a magnetic field. Ferromagnetic clips show deflection and torque in a magnetic field and have the potential to dislodge from the aneurysm. Nonferromagnetic or weakly ferromagnetic aneurysm clips such as the Sugita (Elgiloy), Yasargil (316 LVM stainless steel), Heifetz (Elgiloy), Yasargil (Phynox), and Vari-Angle McFadden (MP35N) do not deflect or deflect weakly in the magnetic field and therefore would not be expected to dislodge during MR. The option of imaging many patients with intracranial aneurysm clips with MR extends the usefulness of the technique to a previously excluded population.     

Alveolar capillary dysplasia with misalignment of the pulmonary veins and hypoplastic left heart sequence caused by an in frame deletion within FOXF1

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a rare, autosomal dominant disorder of interstitial lung development, leading to pulmonary hypertension, and death in infancy. Associated features include malformations of the heart, gastrointestinal tract, and genitourinary system. ACDMPV is caused by heterozygous variants in the FOXF1 gene or microdeletions involving FOXF1. We present a male infant with ACDMPV, hypoplastic left heart sequence (HLHS), duodenal atresia, and imperforate anus due to a de novo, in frame deletion in FOXF1: c.209_214del (p.Thr70_Leu71del). Previous reports have suggested that microdeletions involving FOXF1 are associated with ACDMPV with congenital heart defects, including HLHS, gastrointestinal atresias, and other anomalies; whereas likely pathogenic variants within FOXF1 have not been reported with ACDMPV and HLHS. This is the first patient reported with ACDMPV, HLHS, imperforate anus, and duodenal atresia associated with a likely pathogenic variant in the FOXF1 gene.     

Defects in neurofibromatosis 2 protein function can arise at multiple levels

Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has revealed some general genotype-phenotype correlations. Severe disease has been associated with mutations that produce a premature termination while more mild disease has been associated with missense mutations. Here, we provide experimental proof for these genotype-phenotype correlations by demonstrating that nonsense mutations fail to produce stable merlin protein while missense mutations result in the generation of merlin proteins defective in negative growth regulation. This inability to suppress cell growth may result from defects in the function of merlin at several levels, including failure to form an intramolecular complex. Based on these findings, we propose a model for merlin growth suppression that provides a framework for analyzing NF2 patient mutations and merlin function.      

Alcohol Assessment in Psychiatric Patients

Alcohol use disorders in persons with co-occurring psychiatric disorders are associated with high rates of psy-chosocial instability and poorer treatment outcomes. Thus, assessment of alcohol use and abuse should become an integral part of psychiatric care. Because setf-report-based measures are frequently used, issues of reliability and validity in this population should be critically examined. The purpose of this article is to review and critique the existing empirical literature that has evaluated the psychometric integrity of self- report-based measures in psychiatric settings, and to outline a research agenda that promises to enhance the accuracy of alcohol assessment by persons receiving psychiatric treatment.     

Gamma interferon-activated human macrophages and Toxoplasma gondii, Chlamydia psittaci, and Leishmania donovani: antimicrobial role of limiting intracellular iron.

Iron-saturated transferrin did not reverse the intracellular killing or inhibition of Toxoplasma gondii, Chlamydia psittaci, or Leishmania donovani by gamma interferon-activated human macrophages. Deferoxamine, an iron chelator, also did not impair replication within unstimulated macrophages. Limiting the availability of intracellular iron is an unlikely mechanism in human macrophage activity against these three diverse pathogens.