Mark S. McAllister

A new dynamic in vitro model for the multidimensional study of astrocyte-endothelial cell interactions at the blood-brain barrier.

Blood-brain barrier endothelial cells are characterized by the presence of tight intercellular junctions, the absence of fenestrations, and a paucity of pinocytotic vesicles. The in vitro study of the BBB has progressed rapidly over the past several years as new cell culture techniques and improved technologies to monitor BBB function became available. Studies carried out on viable in vitro models are set to accelerate the design of drugs that selectively and aggressively can target the CNS. Several systems in vitro attempt to reproduce the physical and biochemical behavior of intact BBB, but most fail to reproduce the three-dimensional nature of the in vivo barrier and do not allow concomitant exposure of endothelial cells to abluminal (glia) and lumenal (flow) influences. For this purpose, we have developed a new dynamic in vitro BBB model (NDIV-BBB) designed to allow for extensive pharmacological, morphological and physiological studies. Bovine aortic endothelial cells (BAEC) developed robust growth and differentiation when co-cultured alone. In the presence of glial cells, BAEC developed elevated Trans-Endothelial Electrical Resistance (TEER). Excision of individual capillaries proportionally decreased TEER; the remaining bundles were populated with healthy cells. Flow played an essential role in EC differentiation by decreasing cell division. In conclusion, this new dynamic model of the BBB allows for longitudinal studies of the effects of flow and co-culture in a controlled and fully recyclable environment that also permits visual inspection of the abluminal compartment and manipulation of individual capillaries.

Mechanisms of glucose transport at the blood-brain barrier: an in vitro study.

How the brain meets its continuous high metabolic demand in light of varying plasma glucose levels and a functional blood-brain barrier (BBB) is poorly understood. GLUT-1, found in high density at the BBB appears to maintain the continuous shuttling of glucose across the blood-brain barrier irrespective of the plasma concentration. We examined the process of glucose transport across a quasi-physiological in vitro blood-brain barrier model. Radiolabeled tracer permeability studies revealed a concentration ratio of abluminal to luminal glucose in this blood-brain barrier model of approximately 0.85. Under conditions where [glucose](lumen) was higher than [glucose](ablumen), influx of radiolabeled 2-deoxyglucose from lumen to the abluminal compartment was approximately 35% higher than efflux from the abluminal side to the lumen. However, when compartmental [glucose] were maintained equal, a reversal of this trend was seen (approximately 19% higher efflux towards the lumen), favoring establishment of a luminal to abluminal concentration gradient. Immunocytochemical experiments revealed that in addition to segregation of GLUT-1 (luminal>abluminal), the intracellular enzyme hexokinase was also asymmetrically distributed (abluminal>luminal). We conclude that glucose transport at the CNS/blood interface appears to be dependent on and regulated by a serial chain of membrane-bound and intracellular transporters and enzymes.

Chemical Dependency Treatment Outcomes of Residents in Anesthesiology: Results of a Survey

Substance abuse is a potentially lethal occupational hazard confronting anesthesiology residents. We present the results of a survey sent to all United States anesthesiology training programs regarding experience with and outcomes of chemically dependent residents from 1991 to 2001. The response rate was 66%. Eighty percent reported experience with impaired residents and 19% reported at least one pretreatment fatality. Despite this familiarity, few programs required pre-employment drug testing or used substance abuse screening tools during interviews. The majority of impaired residents attempted reentry into anesthesiology after treatment. Only 46% of these were successful in completion of anesthesiology residency. Eventually, 40% of residents who underwent treatment and returned to medical training entered another specialty. The mortality rate for the remaining anesthesiology residents was 9%. Long-term outcome was reported for 93% of all treated residents. Of these, 56% were successful in some specialty of medicine at the end of the survey period. We hypothesize that specialty change afforded substantial improvement in the overall success rate and avoided significant mortality. Redirection of rehabilitated residents into lower-risk specialties may allow a larger number to achieve successful medical careers.

Chloroquine psychosis masquerading as PCP: a case report.

Abstract Chloroquine and its derivatives have been drugs of choice in the prophylaxis and treatment of malaria for over 50 years. These drugs are also frequently used in the treatment of various rheumatologic disorders. Because many Americans now travel abroad and may require chloroquine prophylaxis, as well as the fact that such medications are readily available through Internet-based supply houses, clinicians should be aware of the potential toxicity associated with the use of these agents. We present the case of an adolescent female who presented with acute, chloroquine-induced toxic psychosis resembling that induced by phencyclidine (PCP) in clinical presentation and laboratory findings. In the acute setting, the differentiation between chloroquine toxic psychosis and PCP psychosis may be difficult. Therefore, the syndrome of chloroquine-induced psychosis is reviewed and its differentiation from PCP psychosis highlighted as it relates to important aspects of this case.

Anabolic-Androgenic Steroid Abuse by Physicians

Abstract Physicians are not immune to the rising popularity of anabolic-androgenic steroid (AAS) abuse. We present three cases of physician-patients who recently required inpatient substance abuse treatment stemming from the abuse of AAS or related compounds. These individuals shared a number of clinical and psychological features that led to or resulted from their abuse of ergogenic substances. Each incurred severe professional, legal, domestic and/or health consequences as a result of their abuse. The common features identified in these patients suggest the presence of an overriding “risk behavior syndrome” that may predispose susceptible individuals to AAS abuse. The reinforcing properties of AAS and the potential for dependence remains an active area of research. Effective treatment of these individuals requires recognition of the causative factors as well as the high likelihood of other substance abuse that must also be addressed. With proper support and monitoring, these individuals can resume productive professional careers.

Patient-provider e-mail communication as an adjunctive tool in addiction medicine.

Abstract Frequent electronic mail communication between patients and their addiction specialist can be utilized as an adjunct in the treatment of alcohol or substance dependency. Selected patients benefit from mandatory daily electronic mail communications with their provider through enhanced accountability, frequent self-assessment, deterrents to isolation, and a sense of continuous access to care. Participants have found the experience easy and enjoyable and all have maintained continuous sobriety. We present our experience using this modality as a series of illustrative case reports and a discussion of the implications of using electronic mail with patients in addiction medicine

Drug Abuse and Addiction

People from all walks of life can experience problems with their drug use, regardless of age, race, background, or the reason they started using drugs in the first place. Some people experiment with recreational drugs out of curiosity, to have a good time, because friends are doing it, or to ease problems such as stress, anxiety, or depression. However, it’s not just illegal drugs, such as cocaine or heroin, that can lead to abuse and addiction. Prescription medications such as painkillers, sleeping pills, and tranquilizers can cause similar problems. In fact, next to marijuana, prescription painkillers are the most abused drugs in the U.S. and more people die from overdosing powerful opioid painkillers each day than from traffic accidents and gun deaths combined. And addiction to opioid painkillers can be so powerful it has become the major risk factor for heroin abuse.