Enhanced hemolysis in pediatric patients requiring extracorporeal membrane oxygenation and continuous renal replacement therapy

PURPOSE: Hemolysis during extracorporeal membrane oxygenation (ECMO) may be associated with the development of hemoglobinuria (Hb) nephropathy and acute renal failure. For patients requiring ECMO, continuous renal replacement therapy (CRRT) can be simultaneously performed by attaching a hemofilter to the ECMO circuit, thereby shunting part of the ECMO blood flow through the hemofilter. However, the possibility that CRRT may further enhance hemolysis (and the risk of Hb nephropathy) in patients on ECMO has not been previously investigated. METHODS: Medical records of 42 children (1 day-12 years old) who required ECMO (ECMO group, n=25) or ECMO and CRRT (ECMO+CRRT group, n=17) after cardiac surgery were reviewed. RESULTS: Forty-one out of 42 patients had elevated plasma-free hemoglobin (FHb) on the first day of ECMO. For all subjects, peak change (mean+/-SD) in FHb (Peak%C-FHb, 83.6+/-183%) correlated with serum lactic dehydrogenase (150+/-324%, r=0.49, p<0.05) and marginally with ECMO blood flow rate (BFR) (Peak%C-BFR, 36.8+/-51.0%, r=0.29, p=0.06). Compared with the ECMO group, the ECMO+CRRT group had a higher Peak%C-FHb (160+/-259%, p<0.05) and Peak%C-BFR (62+/-64%, p<0.05). Also, there was a significant increase in FHb one day after the initiation of CRRT compared with the level prior to CRRT (73.3+/-49.2 vs. 50.0+/-30.3 mg/dL, respectively, p=0.012). Serum creatinine (but not blood urea nitrogen) was significantly higher in the ECMO+CRRT group compared with the ECMO group. The percent change in serum creatinine during ECMO did not correlate with Peak%C-FHb in the ECMO group. CONCLUSION: Our findings suggest that there is enhanced hemolysis during combined ECMO and CRRT compared with ECMO alone. However, the clinical impact of increased hemolysis on renal function in patients receiving ECMO with or without CRRT remains to be determined.     

Age-Dependent Accumulation of Hybrid Vasopressin-Oxytocin Gene Products but not Hybrid Oxytocin-Vasopressin Products in the Endoplasmic Reticulum of Brattleboro Rats

The age-dependence of the incidence of magnocellular neurosecretory neurons containing abnormal accumulations of peptide in the rough endoplasmic reticulum was examined in homozygous Brattleboro rats and in their wild-type Long Evans counterparts. Neurons in which the immunophenotype of the peptide aggregates indicate that somatic cross-over mutations involving the 5' end of the vasopressin gene and the 3' end of the oxytocin gene have occurred, increased with age in homozygous Brattleboro rats, reaching a maximum of 24 cells per hypothalamus (approximately 0.6% of the vasopressin neurons). The increase occurred in both male and female animals but was significantly greater in females. The average incidence of such cells was 6 times greater in the supraoptic than in the paraventricular nucleus. No such cells could be detected in either nucleus of Long Evans rats despite the evidence for hybrid mRNA in these animals. Moreover, no accumulation of peptide translated from the hybrid mRNAs derived from the 5' end of the oxytocin gene and the 3' end of the vasopressin gene could be detected in either Brattleboro or Long Evans animals. These results strongly suggest that the accumulation of peptide in the rough endoplasmic reticulum of vasopressin neurons in homozygous Brattleboro rats is due to an abnormality other than the somatic crossing-over mutation. A second type of abnormal magnocellular neuron with accumulations of peptide in the rough endoplasmic reticulum, in which the immunophenotype of the peptide reveals products derived only from the oxytocin precursor, was present in both Long Evans and Brattleboro rats, but did not increase with age in Brattleboro rats. The incidence of these cells was similar in the supraoptic and paraventricular nuclei.     

Fatal craniocervical necrotizing fasciitis in an immunocompetent patient: A case report and literature review

Background. Craniocervical necrotizing fasciitis (CCNF) is a rapidly progressive, severe bacterial infection of the superficial fascial planes of the head and neck. Group A beta–hemolytic Streptococcus, staphylococcus aureus, and obligate anaerobic bacteria are common pathogens. The disease usually results from a dental source or facial trauma. Extensive fascial necrosis and severe systemic toxicity are common manifestations of CCNF. Recently the lay press has referred to necrotizing fasciitis in several articles about “flesh eating” bacteria, which have resulted in several deaths. Methods. We report the first case of a fatality in an otherwise immunocompetent patient. The patient was a 66-year-old black man with no identifiable source of infection and no history or evidence of immunocompromising disorders. Results. Despite aggressive surgical debridement and broad-spectrum antibiotic coverage, he died 30 hours after admission from multisystem organ failure secondary to overwhelming sepsis. Conclusion. Treatment consists of early recognition of CCNF combined with aggressive surgical debridement and drainage of the involved necrotic fascia and tissue along with broad-spectrum intravenous antibiotic coverage. Although 11 other fatal cases of CCNF have been previously reported, all had an underlying medical problem which created an immunocompromised state, usually diabetes mellitus or chronic alcoholism. We present a case report and literature review along with a discussion of the related anatomy. © 1995 Jons Wiley & Sons, Inc.     

Implications of a diagnosis of anorexia nervosa in a ballet school

Competitive pressures to achieve a slim body shape may be of importance in the etiology of eating disorders in ballet dancers. This study examines the presence of anorexia nervosa-like symptoms in a group of 49 female ballet students (mean age = 18.9 years, SD ± 1.9). All students were assessed for certain physical (weight and height) and psychological (Eating Attitude Test [EAT]) indices at the start of their academic training year. Thereafter, all subjects who presented with anorexia nervosa-like symptoms (EAT ≥ 30, and/or with current secondary amenorrhea or primary amenorrhea if aged 16 years or over) at the initial assessment, were invited for a semistructured interview (Morgan-Russel scales) to determine their diagnostic status. Another aim of the study was to assess the prognostic implications of a diagnosis of anorexia nervosa in this sample. All subjects previously interviewed were invited for a follow-up assessment at 10 months. Anorexia nervosa could be diagnosed in 2 students (4.1%), whilst another 4 students (8.2%) presented with “partial syndrome” anorexia nervosa. All diagnosed students managed to complete their academic training year. The development and implications of a diagnosis of anorexia nervosa in the ballet students are discussed.     

Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Conus medullaris injury following both tetracaine and lidocaine spinal anesthesia

Multiple reports of cauda equina syndrome and transient radicular nerve root irritation have suggested that lidocaine spinal anesthesia may be responsible. In this case report, a patient with a preexisting diabetic neuropathy received a partial block following a tetracaine spinal, which was followed by a lidocaine spinal. Following block resolution, a new conus medullaris syndrome was diagnosed. Because of the close proximity of the cauda equina and the conus medullaris, differentiation between these syndromes can be difficult. The preexisting diabetic neuropathy may have predisposed this patient to neurologic injury. The choice of a different local anesthetic drug with less neurotoxic potential such as bupivacaine may have prevented this injury.     

Burden of injuries and diseases in Yunnan Tin Miners

The burden of injuries is underestimated to an even greater extent in developing countries than in industrialized countries. The objective of this paper is to analyze injuries and diseases in the monitored work place of the world's largest tin mining operation in Yunnan, South China.     

Fine mapping of the spatial relationship between acute ischemia and dendritic structure indicates selective vulnerability of layer V neuron dendritic tufts within single neurons in vivo.

We have evaluated the spatial relationship between clotted vasculature and the structural integrity of layer V cortical neurons in YFP (yellow fluorescent protein)-H transgenic mice 2 to 10 h after photothrombotic stroke. Fortuitously, ischemic zones could be finely mapped about dysmorphic YFP labeled axons and dendrites using histology since Texas-red dextran used to assess blood flow in vivo was trapped within fixed clotted vessels. Ischemic damage to layer V neurons located at the border of ischemia was contained within apical tuft spiny dendritic structures and did not propagate to spines on the more proximal region of the apical dendrite. The lateral spread of dendritic damage decayed sharply with distance from the edge of ischemia (50% reduction in beaded dendrites within approximately 100 microm) and increased with time up to 6 h after stroke but not thereafter. Axonal damage also increased with time but extended further laterally than dendritic damage, up to 500 microm from the stroke core. Apoptotic and necrotic cell death cascades were activated 6 h after stroke; however, only within 300 microm of the ischemic core. These data suggest that the axonal and dendritic circuitry of neurons located 300 microm outside of an ischemic zone can be relatively free of damage or commitment to cell death suggesting that they may be in an ideal position to contribute to functional recovery. Given that ischemic damage may have a larger effect on circuitry involving superficial dendrites and projecting axons, it is conceivable that surviving peri-infarct neurons may have unique structural and functional properties.