Cristiano Gandini

Early acute necrosis, delayed apoptosis and cytoskeletal breakdown in cultured cerebellar granule neurons exposed to methylmercury

Cerebellar granule cells (CGCs) are a sensitive target for methylmercury (MeHg) neurotoxicity. In vitro exposure of primary cultures of rat CGCs to MeHg resulted in a time‐ and concentration‐dependent cell death. Within 1 hr exposure, MeHg at 5–10 μM caused impairment of mitochondrial activity, de‐energization of mitochondria and plasma membrane lysis, resulting in necrotic cell death. Lower MeHg concentrations (0.5–1 μM) did not compromise cell viability, mitochondrial membrane potential and function at early time points. Later, however, the cells progressively underwent apoptosis and 100% cell death was reached by 18 hr treatment. Neuronal network fragmentation and microtubule depolymerization were detected as early as within 1.5 hr of MeHg (1 μM) exposure, long before the occurrence of nuclear condensation (6–9 hr). Neurite damage worsened with longer exposure time and proceeded to the complete dissolution of microtubules and neuronal processes (18 hr). Microtubule stabilization by taxol did not prevent MeHg‐induced delayed apoptosis. Similarly ineffective were the caspase inhibitors z‐VAD‐fluoromethylketone and z‐DEVD‐chloromethylketone, the L‐type calcium channel inhibitor nifedipine, the calcium chelator EGTA and BAPTA, and the NMDA receptor antagonist MK‐801. On the other hand, insulin‐like growth factor‐I partially rescued CGCs from MeHg‐triggered apoptosis. Altogether these results provide evidence that the intensity of MeHg insult is decisive in the time of onset and the mode of neuronal death that follows, i.e., necrosis vs. apoptosis, and suggest that cytoskeletal breakdown and deprivation of neurotrophic support play a role in MeHg delayed toxicity. J. Neurosci. Res. 59:775–787, 2000

Cardiac damage in pediatric carbon monoxide poisoning

Background: Cardiovascular disorders including myocardial ischemia and heart failure have been described in both laboratory animals and humans following carbon monoxide poisoning. Carbon monoxide cardiotoxicity may be clinically occult and often remains undiagnosed because of the lack of overt symptoms and specific ischemic changes in the electrocardiogram. Routine myocardial necrosis markers have low diagnostic efficiency, particularly in patients with concomitant skeletal muscle necrosis or multiple organ failure complicating carbon monoxide poisoning. Carbon monoxide-induced cardiotoxicity has been investigated rarely in children. Case Report: This paper describes carbon monoxide poisoning in a 12-year-old child who suffered from occult cardiac damage despite mild symptoms and low carboxyhemoglobin concentrations. Myocardial and mitral valve dysfunctions were observed, suggesting an ischemia-like syndrome. Cardiac damage was completely reversible within 1 month. Conclusion: This case report supports that a prolonged carbon monoxide exposure can cause cardiac damage in children even in the absence of specific symptoms, cerebral failure and high carboxyhemoglobin concentrations.

Noninvasive Continuous Positive Airway Pressure in Acute Respiratory Failure: Helmet Versus Facial Mask

OBJECTIVE: Noninvasive continuous positive airway pressure (nCPAP) is applied through different interfaces to treat mild acute respiratory failure (ARF) in infants. Recently a new pediatric helmet was introduced in clinical practice to deliver nCPAP. The objective of this study was to compare the feasibility of the delivery of nCPAP by the pediatric helmet with delivery by a conventional facial mask in infants with ARF. PATIENTS AND METHODS: We conducted a single-center physiologic, randomized, controlled study with a crossover design on 20 consecutive infants with ARF. All patients received nCPAP by helmet and facial mask in random order for 90 minutes. In infants in both trials, nCPAP treatment was preceded by periods of unassisted spontaneous breathing through a Venturi mask. The primary end point was the feasibility of nCPAP administered with the 2 interfaces (helmet and facial mask). Feasibility was evaluated by the number of trial failures defined as the occurrence of 1 of the following: intolerance to the interface; persistent air leak; gas-exchange derangement; or major adverse events. nCPAP application time, number of patients who required sedation, and the type of complications with each interface were also recorded. The secondary end point was gas-exchange improvement. RESULTS: Feasibility of nCPAP delivery was enhanced by the helmet compared with the mask, as indicated by a lower number of trial failures (P < .001), less patient intolerance (P < .001), longer application time (P < .001), and reduced need for patient sedation (P < .001). For both delivery methods, no major patient complications occurred. CONCLUSIONS: The results of this current study revealed that the helmet is a feasible alternative to the facial mask for delivery of nCPAP to infants with mild ARF.

Mild ciguatera poisoning: Case reports with neurophysiological evaluations.

Ciguatera poisoning causes mainly gastrointestinal and neurological effects of variable severity. However, symptoms of peripheral neuropathy with paresthesias and paradoxical disturbance of thermal sensation are the hallmark. Electrophysiological studies are often normal, except in severe cases. We report four people who developed mild ciguatera poisoning after barracuda ingestion. Electrophysiological studies documented normocalcemic latent tetany. These findings are consistent with ciguatoxins mechanism of toxicity, which involves inactivation of voltage‐gated Na+ channels and eventually increases nerve membrane excitability.

Implementing a global integrative rehabilitation medicine rotation: a physical medicine and rehabilitation residency program's experience.

ABSTRACTAn innovative international rotation in integrative rehabilitation medicine was implemented as part of the physical medicine and rehabilitation residency program at the Medical College of Wisconsin. Rotation objectives were to introduce medical knowledge of integrative medicine treatments into physical medicine and rehabilitation practice and to initiate collaboration with international academic partners. Residents were approved based on their academic record, completion of prerequisites, and personal statement. During a 4-wk rotation located in Italy, residents developed an integrative treatment strategy for each patient using conventional medical care and other therapeutic options, including acupuncture, biofeedback, aquatic therapy, yoga, and others. Postrotation assessment included evaluations by Italian team and patients, residents’ evidence-based presentations, and postrotation self-reflection. Participating residents reported high achievement in clinical performance, improved application of integrative medicine, broader appreciation of cultural diversity in patient care, and increased personal and professional development. This reciprocal program model serves as an example for other programs interested in implementing similar international rotations.

Re: Alternative medicines: Yes; Alternatives to medicine: No

It is important to highlight three main points in our response. Our manuscript, BImplementing a Global Integrative Rehabilitation Medicine Rotation: A Physical Medicine and Rehabilitation Residency Program’s Experience[ describes first and foremost a global health resident experience and faculty teaching collaboration, with clearly defined resident learning goals and objectives based on ACGME competencies. Second, it describes resident exposure to integrative medicine, within an established successful group practice. Finally, the manuscript is descriptive, not a research article addressing the efficacy or safety of complementary and alternative medicine and, therefore, cannot be viewed in such a manner. A clear definition of integrative medicine and its tenets has been previously described and form an important component of Bpatient-centered care.[ The Veterans Health Administration is applying these concepts while embarking on a transformation of health care, to drive the current model that is primarily Bfind it, fix it[ disease care to a personalized, proactive approach that is driven by the individual needs of the Veteran. An in-depth study of each and all of these complementary and alternative medicine practices is not possible during a 4-week rotation and is not a rotation learning goal. Careful selections of the techniques and teachers who deliver them within the integrative group, as well as ongoing formation by means of in-service journal clubs, discussion groups, and cross-participation among the practices, are the cornerstones of our integrative medicine experience. The focus of both the outpatient and inpatient experiences is to create clarity of thought in prescribing comprehensive medical treatment, for an effective, precise prescription of pharmacologic agents, allopathic treatments, modalities, or exercise based on individualized patient assessment and goals. The integrative approach is a philosophy, not a series of techniques to be memorized and applied as mere protocol, reflecting the concept that Bthe whole is greater than the sum of its parts.[ We agree that the conventional standards of evidencebased medicine need to be applied equivalently to all areas of medical care, including complementary and alternative medicine. Further research addressing patient safety, efficacy, and cost effectiveness is needed and desired. Ongoing resident education must teach and practice critical review of the scientific literature, including the application of complementary and alternative medicine techniques.