Pharmacokinetic transfer functions and generalized clearances

A generalized steady-state clearance coefficient is defined to relate drug or metabolite mass transfer rates into one area of the body (area II) to the constant drug concentration in another area (area I). It is demonstrated that this clearance coefficient may be used in the transient case to calculate total mass transfer into area II when the drug AUC in area I is known. This generalizes the well-known "clearance formula" CL = Ae/AUC to cases in which several compartments separate areas I and II, as well as to cases where distributed models are preferred. Several applications are discussed, including a noninvasive means of determining the fraction absorbed of topically administered drugs.     

Hostage hallucinations. Visual imagery induced by isolation and life-threatening stress

The literature on hallucinatory experiences of hostage victims is reviewed. The phenomenology is examined in 30 case studies involving 31 persons, including ex-prisoners of war and victims of rape, kidnapping, terrorism, robbery, and "UFO abductions." The victims were subjected to conditions of isolation, visual deprivation, restraint on physical movement, physical abuse, and the threat of death. For eight victims, these conditions were sufficient to produce a progression of visual hallucinations from simple geometric images to complex memory images coupled with dissociation. The other 23 victims, subjected to similar conditions but without isolation and life-threatening stress, resulting from the threat of death, did not experience hallucinations. The hostage hallucinations are compared to those resulting from sensory deprivation, near fatal accidents, and other states of isolation and stress. A common mechanism of action based on entoptic phenomena and CNS excitation and arousal is suggested.     

The Alpha-Defensin Prosthetic Joint Infection Test Has Poor Validity for Native Knee Joint Infection

BackgroundThe alpha-defensin test known as Synovaure has been very effective in diagnosis of prosthetic joint infections (PJIs). Being able to easily and accurately differentiate septic and inflammatory arthropathies in native joints would improve diagnostic workup and management. We tested the ability of an alpha-defensin test to distinguish septic from inflammatory or crystalline arthropathy in the native knee.Methods40 native knee joint fluid specimens were tested with cell count, fluid analysis, and culture and alpha-defensin testing. We determined the sensitivity and specificity of the alpha-defensin test using culture-positive fluid as the gold standard for septic arthropathy and positive crystals as the gold standard for crystalline arthropathy.ResultsThe Synovasure PJI test had 100% specificity for septic arthritis coupled with a 28% false-positive rate when applied to native knee aspirations. False-positive rate was 5.3 times higher in patients with crystals found in the joint fluid.ConclusionAlpha-defensin testing, in the form of the Synovasure PJI test, has a high-false-positive rate when used to distinguish septic and inflammatory arthritis in the native knee joint. Future work will need to determine the sensitivity and specificity of the newer native joint panel. Clinicians should be cognizant of the specific alpha-defensin test used when sampling native knee synovial fluid.     

Impaired Induction of the Apoptosis-Protective Protein Bcl-xL in Activated PBMC from Asymptomatic HIV-Infected Individuals

Progression to AIDS in asymptomatic HIV-infected individuals is characterized by a gradual but progressive loss of CD4⁺ T cells. While the mechanisms underlying this decline are currently unknown, recent evidence suggests that these cells are abnormally sensitive to apoptosis in response to activation signals. Recent work has implicated downregulation of Bcl-2 with the increased spontaneous apoptosis in lymphocytes from HIV-infected patients. We have evaluated the roles of the apoptosis-protective proteins Bcl-2 and Bcl-x in stimulated PBMC from asymptomatic HIV-infected and HIV-uninfected individuals. We found that Bcl-2 was constitutively expressed in PBMC from both HIV-infected and uninfected samples. However, Bcl-x induction was delayed and responses were decreased in stimulated HIV-infected samples. Additionally, single-cell intracellular staining of Bcl-x revealed a significant inverse correlation between PWM-induced Bcl-x expression and apoptosis (r = –0.695, P = 0.005). This was confirmed at the single-cell level in direct experiments when stimulated cells were sorted based on Bcl-x induction and then measured for apoptosis. Furthermore, low Bcl-x expression was not due to reduced lymphocyte activation following PWM stimulation. Our data indicate that the induction of Bcl-x is markedly impaired in asymptomatic HIV-infected patients and that stimuli which induce inadequate expression of Bcl-x are associated with increased levels of apoptosis in these cells.     

Thymic masses on MR imaging

MR imaging is an excellent technique for identifying and defining the extent of thymic tumors. T1-weighted spin-echo MR images (e.g., 600/15 [TR/TE]) best demonstrate tumor extent, and T2-weighted images (e.g., 2500/90 [TR/TE]) help differentiate "cystic" from solid thymic masses. Cyst formation and/or hemorrhage appear as areas of high signal intensity (greater than that of fat) on T2-weighted images. Focal areas of low signal intensity (less than that of muscle) correspond pathologically to fibrous capsules and septa, air, or calcification. In this report, the MR appearance of the normal thymus is reviewed briefly, and the gamut of abnormal thymic masses on MR is illustrated.     

Stent Scraping for Histology: An Alternative Method for Obtaining Tissue to Rule out Neoplasia

Despite improvement in diagnostic modalities, confirmation of a histologic diagnosis of cancer of the biliary tree and pancreas remains elusive. Attempts to collect positive cytology specimens from vigorous brushings or washings obtained at endoscopy or percutaneously are often unsuccessful. In our unit, we have increased the yield by obtaining tissue scraped from prostheses that have been previously placed in either the bile duct or the pancreatic duct. The stents are first flushed with saline to collect cytology specimens, after which, they are bisected and scraped, and these contents are prepared in a manner similar to that used to prepare biopsy samples. Twelve of 16 scraped samples, 9 bile duct and 3 pancreas, were positive for adenocarcinoma. The cytology specimens were positive in only 4 of the 12. We recommend this method of sampling from material contained within prostheses as an adjunct when previous brushings, washings, or biopsies are negative.