Self-assembled nanofiber hydrogels for mechanoresponsive therapeutic anti-TNFα antibody delivery.

Low molecular weight hydrogels, prepared from glycosyl-nucleoside-lipid amphiphiles, exhibit shear-thinning behaviour and reversible thermally- and mechanically-triggered sol-gel transitions. Using mechanical shear stimulation, the release of entrapped anti-TNFα increases and the released anti-TNFα demonstrates efficacy in in vitro neutralization bioassays. Delivery of anti-TNFα is of general interest and broad medicinal utility for treating autoimmune diseases such as rheumatoid arthritis.

Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure.

This report provides the first detailed neuropathological study of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in humans. All 3 subjects self-administered the drug under the impression it was "synthetic heroin" and subsequently developed severe and unremitting parkinsonism, which was L-dopa responsive, at least in the earlier stages of illness. Survival times ranged from 3 to 16 years. Neuropathological examination revealed moderate to severe depletion of pigmented nerve cells in the substantia nigra in each case. Lewy bodies were not present. In Patients 1 and 2, there was gliosis and clustering of microglia around nerve cells. Patient 3 had a similar picture and also showed large amounts of extraneuronal melanin. These findings are indicative of active, ongoing nerve cell loss, suggesting that a time-limited insult to the nigrostriatal system can set in motion a self-perpetuating process of neurodegeneration. Although the mechanism by which this occurs is far from clear, the precedent set by the cases could have broad implications for human neurodegenerative disease.

Fatal hypernatremic dehydration in exclusively breast-fed newborn infants due to maternal lactation failure.

Infants who die of hypernatremic dehydration usually demonstrate at autopsy an underlying condition or disease process that predisposes to increased water loss. In the absence of such findings, forensic concerns may focus sharply on parental or caretaker neglect as an underlying cause of death. In this case report, we describe unrecognized fatal hypernatremic dehydration in two exclusively breast-fed neonates due solely to failure of maternal lactation. We further describe epidemiologic and etiologic features of such deaths and discuss forensic difficulties encountered in their certification.

Quinolones for the treatment and prophylaxis of tuberculosis.

Quinolones possess enormous potential as antimycobacterial agents, and have been proven to have excellent in vitro activity against M. tuberculosis, as well as limited in vivo efficacy. These drugs appear to be safe and well tolerated even when taken for an extended period. This is important considering that one of the most significant factors contributing to resistance is compliance. Quinolones exhibit great promise for initial treatment and retreatment of MDRTB, a rapidly growing problem, as well as for prevention. They have shown to be as effective as some of the first-line agents currently used in treating TB. There appears to be overwhelming need to further study these agents and determine their role in the treatment of TB. In the future, quinolones may emerge as first-line therapy for TB.

"Hyperacute" subdural hematoma: CT mimic of recurrent episodes of bleeding in the setting of child abuse.

Mixed density extraaxial hematomae on computed tomography (CT) scanning generally represent recurrent episodes of bleeding (chronic subdural hematoma with rebleeding). Hyperacute hemorrhages in which the patient is actively bleeding or has a coagulopathy have also been described as mixed density. We report a case of child abuse in a fourteen month old child who presented with a CT scan showing a mixed density subdural hematoma which was originally interpreted as recurrent episodes of hemorrhage, but who had evidence of only acute, active bleeding at surgery and by histologic examination. There is a proportionally high incidence of subdural hematoma in cases of child abuse, due in part to the increased susceptibility of the immature brain to trauma. Because the mechanism of injury is different for hemorrhage due to hyperacute subdural hematoma (SDH) and that of acute bleeding within a chronic SDH, the distinction between these entities has potentially important legal implications in cases of suspected child abuse. This potential pitfall in interpretation of the CT scan has not to our knowledge been reported in the forensic literature.

Blunt impact to the chest leading to sudden death from cardiac arrest during sports activities.

BACKGROUND: Sudden death from cardiac arrest in a young person may occur during sports play after a blunt blow to the chest in the absence of structural cardiovascular disease or traumatic injury (cardiac concussion or commotio cordis). We studied the clinical features of this apparently uncommon but important phenomenon. METHODS: We identified cases from the registries of relevant agencies and organizations, as well as newsmedia accounts, and developed a clinical profile of 25 children and young adults, 3 to 19 years of age. RESULTS: Each victim collapsed with cardiac arrest immediately after an unexpected blow to the chest, which was usually inflicted by a projectile (such as a baseball or hockey puck). Incidents took place during organized competitive sports in 16 cases and in recreational settings at home, at school, or on the playground in 9. In each instance, the impact to the chest was not judged to be extraordinary for the sport involved and did not appear to have sufficient force to cause death. Twelve victims collapsed virtually instantaneously on impact, whereas 13 remained conscious and physically active for a brief time before cardiac arrest. Cardiopulmonary resuscitation was administered within about three minutes to 19 victims, but normal cardiac rhythm could be restored in only 2 (both incurred irreversible brain damage and died shortly thereafter). Seven victims (28 percent) were wearing some form of protective chest padding. CONCLUSIONS: We speculate that most sudden deaths related to impact to the chest (not associated with traumatic injury) are due to ventricular dysrhythmia induced by an abrupt, blunt precordial blow, presumably delivered at an electrically vulnerable phase of ventricular excitability. This profile of blunt chest impact leading to cardiac arrest adds to our understanding of the range of causes of sudden death on the athletic field and may help in the development of preventive measures.

Patterns of facial resuscitation injury in infancy.

Cardiopulmonary resuscitation (CPR)-related artifacts in pediatric rescue that have the potential for serious complications in surviving patients have been well described in the medical literature. Medically trivial soft-tissue injuries, especially of the face and neck, carry predominantly forensic significance and have received less attention. We describe such injuries in nine of 25 consecutive cases of infants who received CPR, and correlate those injuries with specific rescue maneuvers. Techniques for effective investigation and interpretation of such injuries are suggested.

Delayed fatal hemothorax due to traumatic carotid dissection: a case report of a previously unreported cause of death.

A unique case of delayed fatal hemothorax in a 12-year-old girl resulting from atypical dissection of a traumatic carotid aneurysm is reported, due to occult neck trauma received in a sledding accident which occurred one week prior to death. Aspects of traumatic carotid dissection and forensic implications of delayed presentation of such findings in the setting of occult trauma are discussed.

Commotio cordis in two amateur ice hockey players despite the use of commercial chest protectors: case reports.

We describe two recent deaths in 15-year-old male ice hockey players. Both adolescents died of commotio cordis from chest impacts by ice hockey pucks despite their use of commercially designed and manufactured chest protectors. Commotio cordis is discussed as a preventable sports-related injury in the adolescent age group, and the need for improved chest protective equipment in preventing such injuries is also examined.

Story processing in right-hemisphere brain-damaged patients.

The understanding of stories requires sensitivity to structural aspects of narrative, the emotional content conveyed by the narrative, and the interaction between structural and emotional facets of the story. Right-hemisphere-damaged (RHD) and normal control subjects performed a number of different analytic tasks which probed their competence at story comprehension. Results revealed that RHD subjects perform at a level comparable to that of normal controls with stories that follow a canonical form and that they show few difficulties with structural aspects of narrative. Contrary to expectation, they are strongly influenced by the "interest" level of a story and by other factors that tap emotional sensitivity. Findings are discussed in terms of the processing and arousal mechanisms which may give rise to the observed pattern of difficulties in RHD patients.

Sensitivity to conversational deviance in right-hemisphere-damaged patients.

To participate meaningfully in conversation, speakers must be sensitive to statements which advance and those which block the direction of a discourse. The effect of right-hemisphere damage (RHD) on sensitivity to conversational advancers and blockers was investigated by asking subjects to interpret normal conversations and conversations which were blocked by violations of Gricean maxims: specifically, tangential and redundant statements. Results indicate that RHD patients function normally in canonical, directed conversation. However, they have difficulty interpreting and judging the effect of blocking statements, particularly with regard to tangentiality. The results are discussed in terms of a mental model of directed conversation which incorporates both structural and affective components.

Pathophysiology of the perioperative low output syndrome.

Surgery in high-risk cardiac patients is now possible due to improvements in medical techniques. These patients are, however, more likely to develop a low cardiac output syndrome in the perioperative period. The condition may be precipitated by surgery, especially in those with underlying ischaemic heart disease, the initial cardiac insult being followed by diminished contractility and compensatory changes in perfusion pressures due to the release of endogenous catecholamines. Catecholamine release induces myocardial irritability and there is a subsequent increase in heart rate and decrease in cardiac output. As a result, contractility may decrease even further, and the downward spiral worsens. This article reviews current progress in the understanding of the pathophysiology of the low cardiac output syndrome with reference to the various parameters used to assess cardiac function, and the effects of drug therapy on these parameters.