Acetaminophen causes neurodevelopmental injury in susceptible babies and children: no valid rationale for controversy.

Despite the worldwide acceptance of acetaminophen (APAP) as a necessary medicine in pediatrics, evidence that early exposure to APAP causes neurodevelopmental injury in susceptible babies and children has been mounting for over a decade. The evidence is diverse and includes extensive work with laboratory animals, otherwise unexplained associations, factors associated with APAP metabolism, and limited studies in humans. Although the evidence has reached an overwhelming level and was recently reviewed in detail, controversy persists. This narrative review evaluates some of that controversy. Evidence from the pre- and postpartum periods was considered to avoid controversy raised by consideration of only limited evidence of risks during the prepartum period. Among other issues, the association between APAP use and the prevalence of neurodevelopmental disorders was considered. A systematic review revealed that the use of APAP in the pediatric population was never tracked carefully; however, historical events that affected its use were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Moreover, problems with the exclusive reliance on results of meta-analyses of large datasets with limited time frames of drug exposure were reviewed. Furthermore, the evidence of why some children are susceptible to APAPinduced neurodevelopmental injuries was examined. We concluded that available evidence demonstrates that early exposure to APAP causes neurodevelopmental injury in susceptible babies and small children.

The Dangers of Acetaminophen for Neurodevelopment Outweigh Scant Evidence for Long-Term Benefits.

Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment. We conclude that the very early postpartum period poses the greatest risk for acetaminophen-induced ASD, and that nearly ubiquitous use of acetaminophen during early development could conceivably be responsible for the induction in the vast majority, perhaps 90% or more, of all cases of ASD. Despite over a decade of accumulating evidence that acetaminophen is harmful for neurodevelopment, numerous studies demonstrate that acetaminophen is frequently administered to children in excess of currently approved amounts and under conditions in which it provides no benefit. Further, studies have failed to demonstrate long-term benefits of acetaminophen for the pediatric population, leaving no valid rationale for continued use of the drug in that population given its risks to neurodevelopment.

Therapeutic doses of acetaminophen with co-administration of cysteine and mannitol during early development result in long term behavioral changes in laboratory rats.

Based on several lines of evidence, numerous investigators have suggested that acetaminophen exposure during early development can induce neurological disorders. We had previously postulated that acetaminophen exposure early in life, if combined with antioxidants that prevent accumulation of NAPQI, the toxic metabolite of acetaminophen, might be innocuous. In this study, we administered acetaminophen at or below the currently recommended therapeutic dose to male laboratory rat pups aged 4-10 days. The antioxidants cysteine and mannitol were included to prevent accumulation of NAPQI. In addition, animals were exposed to a cassette of common stress factors: an inflammatory diet, psychological stress, antibiotics, and mock infections using killed bacteria. At age 37-49 days, observation during introduction to a novel conspecific revealed increased rearing behavior, an asocial activity, in animals treated with acetaminophen plus antioxidants, regardless of their exposure to oxidative stress factors (2-way ANOVA; P < 0.0001). This observation would suggest that the initial hypothesis is incorrect, and that oxidative stress mediators do not entirely eliminate the effects of acetaminophen on neurodevelopment. This study provides additional cause for caution when considering the use of acetaminophen in the pediatric population, and provides evidence that the effects of acetaminophen on neurodevelopment need to be considered both in the presence and in the absence of oxidative stress.

Spontaneous aortic thrombosis in neonates: a case report and review of literature.

Neonatal aortic thrombosis is a rare occurrence but can be life-threatening. Most aortic thrombosis in neonates is related to umbilical artery catheters. A case of a neonate with a spontaneous aortic thrombosis is described here along with a comprehensive review of the literature for cases of neonatal aortic thrombosis not related to any intravascular device or procedure. The aetiologies of these spontaneous thromboses and the relevance of hypercoagulable disorders are discussed. The cases were analysed for odds of death by treatment method adjusted for era. The reference treatment method was thrombolysis and anticoagulation. No other treatment modality had significantly lower odds than the reference. Surgery alone had higher odds for death than the reference, but this may be confounded by severity of case. The management recommendations for clinicians encountering neonates with spontaneous neonatal aortic thrombosis are discussed.

Ventricular fibromas in children, arrhythmia risk, and outcomes: A multicenter study.

BACKGROUND: Although ventricular fibromas are rare, they are the second most common type of cardiac tumor in children. While histologically benign, they have a propensity to cause malignant arrhythmias, with cardiac arrest often being the first presentation. OBJECTIVE: The purpose of this study was to evaluate the arrhythmia risk and management strategies for pediatric ventricular fibromas. METHODS: Fifteen centers in the British Paediatric Arrhythmia Group network were contacted to partake in the study to contribute cases. A detailed database search was performed at 2 hospitals for cases of ventricular fibromas. RESULTS: A total of 19 patients were included in the study. Arrhythmias were common, with 5 patients presenting with cardiac arrest and 5 others having documented ventricular tachycardia. Nine patients have undergone surgical resection at various hospitals, and all these patients have survived with good long-term outcomes. One patient who did not have any treatment died, presumably of a ventricular arrhythmia; another died of metastatic disease. There were no recurrences of arrhythmia after surgery, and the need for a defibrillator was alleviated in all cases. CONCLUSION: Ventricular fibromas have a high propensity to cause malignant arrhythmias, and if they are not managed appropriately, mortality is high. The outcomes of surgical resection are good, regardless of size, and this represents the best therapeutic option, with most patients being symptom free in the longer term.

Dimensional Review of Scales for Forensic Photography.

Scales for photography provide a geometrical reference in the photographic documentation of a crime scene, pattern, or item of evidence. The ABFO No. 2 Standard Reference Scale (1) is used by the forensic science community as an accurate reference scale. We investigated the overall accuracy of the major centimeter graduations, internal/external diameters of the circles, error in placement of the circle centers, and leg perpendicularity. Four vendors were selected for the scales, and the features were measured on a vision-based coordinate measurement system. The scales were well within the specified tolerance for the length graduations. After 4 years, the same scales were measured to determine what change could be measured. The scales demonstrated acceptable stability in the scale length and center-to-center measurements; however, the perpendicularity exhibited change. The study results indicate that scale quality checks using certified metal rulers are good practice.

Is autism a member of a family of diseases resulting from genetic/cultural mismatches? Implications for treatment and prevention.

Several lines of evidence support the view that autism is a typical member of a large family of immune-related, noninfectious, chronic diseases associated with postindustrial society. This family of diseases includes a wide range of inflammatory, allergic, and autoimmune diseases and results from consequences of genetic/culture mismatches which profoundly destabilize the immune system. Principle among these consequences is depletion of important components, particularly helminths, from the ecosystem of the human body, the human biome. Autism shares a wide range of features in common with this family of diseases, including the contribution of genetics/epigenetics, the identification of disease-inducing triggers, the apparent role of immunity in pathogenesis, high prevalence, complex etiologies and manifestations, and potentially some aspects of epidemiology. Fortunately, using available resources and technology, modern medicine has the potential to effectively reconstitute the human biome, thus treating or even avoiding altogether the consequences of genetic/cultural mismatches which underpin this entire family of disease. Thus, if indeed autism is an epidemic of postindustrial society associated with immune hypersensitivity, we can expect that the disease is readily preventable.

Interactions of Hylastes species (Coleoptera: Scolytidae) with Leptographium species associated with loblolly pine decline.

Hylastes spp. (Coleoptera: Scolytidae) were evaluated as potential vectors of Leptographium spp. fungi. Bark beetles were trapped from stands ofloblolly pine, Pinus taeda L., exhibiting a range of decline symptoms in central Alabama. Under controlled conditions, field-collected adult Hylastes salebrosus Eichoff (Coleoptera: Scolytidae) and Hylastes tenuis Eichoff (Coleoptera: Scolytidae), which had been surface-sterilized and inoculated with Leptographium terebrantis Barras & Perry and Leptographium serpens (Goid.) Wingfield, transmitted the fungi into 100% of wounded and unwounded loblolly root sections with which they were confined. None of the sterilized and uninoculated beetles transmitted any Leptographium spp. to roots. Significantly more H. salebrosus and H. tenuis brood emerged from roots infected with Leptographium species than from sterile roots, indicating an enhancement of Hylastes reproduction.

Wound care for elderly patients: advances and clinical applications for practicing physicians.

Chronic ulcers (wounds) are commonly encountered in medical practice, particularly in elderly patients who have chronic medical conditions. Health care providers must be adept at diagnosing chronic ulcers and optimizing medical treatment. We describe the best medical practice for the 4 common types of chronic ulcers: pressure ulcers, ischemic ulcers, venous ulcers, and neuropathic ulcers. We emphasize the importance of nutrition and proper wound care as a foundation for the management of all chronic ulcers. There is a unique therapeutic goal for each chronic ulcer. Pressure relief should be provided for both pressure ulcers and neuropathic ulcers. Ischemic ulcers require revascularization. Patients with venous ulcers need adequate edema control. We outline advances in each of these areas and discuss the newest developments in wound care, including growth factors, hyperbaric oxygen, and vacuum-assisted devices. Chronic ulcers in elderly patients can heal with proper diagnosis and good medical care.

Blue-stain Fungi Associated with Roots of Southern Pine Trees Attacked by the Southern Pine Beetle, Dendroctonus frontalis.

Forty paired plots were established from eastern Texas to Alabama to study root-infecting, blue-stain fungi in southern pine stands undergoing southern pine beetle (SPB) attack. Woody roots were sampled in plots undergoing recent or current attack by the SPB. Comparisons were made between occurrence of Leptographium spp. and related fungi and data on various characteristics of natural stands and plantations studied. Three fungal species, L. terebrantis, L. procerum, and Ophiostoma ips, along with unidentified Leptographium and Graphium species, were isolated from sampled roots. L. terebrantis was isolated more frequently from SPB-attacked plots (P < 0.001) than was either L. procerum or O. ips. More blue-stain fungal species and related genera were isolated from SPB-attacked plots than from control plots (P < 0.001). This also was true for combined isolation percentages of L. terebrantis, L. procerum, and O. ips (P = 0.03). Presence of blue-stain fungi also was associated with higher stand basal area in the control plots (P = 0.045). Isolation frequencies of O. ips and L. procerum, along with the combination of these fungal species with L. terebrantis, were logistically related to increasing stand basal area in the control plots (P = 0.02, 0.02, and 0.01, respectively). No logistic relationship was found for frequency of any of the three blue-stain species with respect to basal area in SPB-attacked plots. These results suggest blue stain fungi are important in the dynamics of susceptibility of southern pines to SPB attack.