Approach to the treatment of cutaneous malignancy in HIV-infected patients

Patients infected with human immunodeficiency virus (HIV) have an increased risk of developing skin cancers. These at-risk patients may have atypical presentations and/or altered clinical courses. This article will review and discuss management issues for the following malignancies: lymphomas, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, and Kaposi's sarcoma.     

Role of paraoxonase (PON1) status in pesticide sensitivity: genetic and temporal determinants

Individual differences in detoxication capacities for specific organophosphorous (OP) compounds are due largely to differences in catalytic efficiency or abundance of the HDL-associated enzyme, paraoxonase (PON1). First, we provide evidence that children less than 2 years of age represent a particularly susceptible population for OP exposure due to low abundance of PON1 and variable onset of plasma PON1 activity. Second, we describe studies examining the neurotoxic effects of chronic, low-level OP pesticide exposure in mice. PON1 knockout (PON1(-/-)) and wild-type mice were exposed chronically (PN4 to PN21) to low levels of chlorpyrifos oxon (CPO). Endpoints included cholinesterase activity, histopathology, gene expression, and behavior. Even at PN4, when PON1 levels were low in wild-type mice, PON1(-/-) mice were more sensitive to inhibition of brain cholinesterase by CPO. At PN22, and persisting as long as 4 months, chronic developmental exposure to 0.18 mg/kg/d or 0.25 mg/kg/d CPO resulted in perinuclear vacuolization of cells in a discrete area of the neocortex and irregular distribution of neurons in the cortical plate, with an increase in the number of affected cells at 0.25mg/kg/d. Third, we describe a transgenic mouse model in which human transgenes encoding either hPON1Q192 or hPON1R192 were expressed at equal levels in place of mouse PON1. The developmental onset of expression followed the mouse time course and was identical for the two transgenes, allowing these mice to be used to assess the importance of the Q192R polymorphism during development. Adult mice expressing hPON1R192 were significantly more resistant than hPON1Q192 mice to CPO toxicity. Our studies indicate that children less than 2 years old, especially those homozygous for PON1Q192, would be predicted to be particularly susceptible to CPO toxicity.     

Fatal community-associated methicillin-resistant Staphylococcus aureus pneumonia in an immunocompetent young adult

Severe pneumonia caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) was reported in children soon after this pathogen emerged in the United States in the 1990s. Genes for Panton Valentine leukocidin, which are present in the majority of community-associated MRSA, are thought to enhance the ability of S aureus to cause necrotizing pneumonia. Despite the rapid spread throughout the United States of community-associated MRSA and related skin and soft-tissue infections, reports of severe pneumonia in adults have been rare. We describe a case of a healthy young adult who initially was treated as an outpatient with levofloxacin for what appeared to be typical community-acquired pneumonia. He soon returned to the emergency department (ED) with rapidly fatal necrotizing pneumonia, associated with hemoptysis, leukopenia, and sepsis syndrome, that was caused by community-associated MRSA carrying genes for Panton Valentine leukocidin. This case highlights the typical features of this form of pneumonia and the need to consider MRSA when evaluating and treating severe pneumonia in the ED. It also raises the question of whether the incidence of this form of pneumonia might be increasing in communities with a high prevalence of community-associated MRSA and whether current pneumonia treatment guidelines should be modified.     

Selective attention in young women awakened from nocturnal sleep

BACKGROUND: Selective attention, the ability to focus on relevant stimuli for information processing while ignoring irrelevant stimuli, is pertinent to many human activities. However, there have been few attempts to measure circadian influences on selective attention. METHODS: As part of a larger protocol, 14 female subjects spent 3 nights at a General Clinical Research Center. On a given night, subjects were awakened at either 24:00, 03:00, or 06:00 hours and administered a computerized flankers task using two levels of spacing for the flankers ("near", 0.75 degrees; and "far", 1.5 degrees) and three types of flanker trials (compatible, incompatible, and neutral). Before sleeping on the first or second night, subjects were also administered the flankers task at 21:00. RESULTS: Neutral flanker trials resulted in faster reaction times (RTs) at 21:00 than the three nighttime conditions. The flanker effect (i.e., the difference between compatible and incompatible trials) was also significantly smaller in the 21:00 condition, but did not differ among the other three conditions. An effect component analysis indicated significantly more interference than facilitation. For incompatible/far trials, there was a trend toward a slowing down of RT across the four time conditions. CONCLUSION: The present study demonstrated that the flankers task, which measures selective attention, may be a relevant measure of performance in circadian studies. The analyses suggest increases in RT if subjects are awakened from a bout of sleep, and if these results are confirmed, failures of selective attention mechanisms to inhibit stimuli that require a competing response when subjects are awakened from sleep.     

Psychiatric and psychological management considerations associated with nerve damage and neuropathic trigeminal pain

This article reviews current models of neuropathic pain and relates recent research in the neurobiology of pain to improved understanding of psychiatric and psychological aspects and treatment of chronic aspects of pain. Some of the anomalies associated with beliefs about chronic pain are also outlined. In particular, the notion that pain is either verifiable or due to psychiatric disturbance is laid to rest; the onus is on the clinician to understand and treat the patient with sensitivity, rather than on the patient to provide proof of pain.     

Peripheral venous pressure as a measure of venous compliance during pheochromocytoma resection

Venous pressures measured from peripheral venous catheters (PVP) closely estimate the central venous pressure (CVP) in surgical and critically ill patients. CVP is often used to estimate intravascular volume; however, fluctuations of CVP may also be induced by changes in venous tone caused by alpha-adrenergic catecholamine stimulation. We simultaneously monitored PVP, CVP, and mean arterial blood pressure during resection of pheochromocytoma in a 63-yr-old woman and found excellent correlation between the three pressure variables, suggesting that fluctuations of PVP reflect overall changes in vascular tone.     

GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain

Establishing the cellular identity in vivo of adult multipotent neural progenitors is fundamental to understanding their biology. We used two transgenic strategies to determine the relative contribution of glial fibrillary acidic protein (GFAP)-expressing progenitors to constitutive neurogenesis in the adult forebrain. Transgenically targeted ablation of dividing GFAP-expressing cells in the adult mouse subependymal and subgranular zones stopped the generation of immunohistochemically identified neuroblasts and new neurons in the olfactory bulb and the hippocampal dentate gyrus. Transgenically targeted cell fate mapping showed that essentially all neuroblasts and neurons newly generated in the adult mouse forebrain in vivo, and in adult multipotent neurospheres in vitro, derived from progenitors that expressed GFAP. Constitutively dividing GFAP-expressing progenitors showed predominantly bipolar or unipolar morphologies with significantly fewer processes than non-neurogenic multipolar astrocytes. These findings identify morphologically distinctive GFAP-expressing progenitor cells as the predominant sources of constitutive adult neurogenesis, and provide new methods for manipulating and investigating these cells.     

Genome-scan for loci involved in cleft lip with or without cleft palate in consanguineous families from Turkey

The medical care of patients affected by rare disorders depends heavily on experiences garnered from prior cases, including those patients evaluated by the treating physician and those published in the medical literature. The utility of published cases is wholly dependent upon accurate diagnosis of those patients. In our experience, the rate of misdiagnosis in Proteus syndrome (PS) is high. Diagnostic criteria have been published, but these criteria have not been applied consistently and were published after many case reports appeared in the literature. We reviewed 205 cases of individuals reported to have PS in the literature and three of us independently applied the diagnostic criteria to these case reports. Our initial diagnostic congruence was 97.1% (199/205); the discrepancies in six cases were easily resolved. Only 97 (47.3%) of reported cases met the diagnostic criteria for PS; 80 cases (39%) clearly did not meet the criteria; and although 28 cases (13.7%) had features suggestive of PS, there were insufficient clinical data to make a diagnosis. Reported cases that met the PS criteria had a higher incidence of premature death, and other complications (scoliosis, megaspondyly, central nervous system abnormalities, tumors, otolaryngologic complications, pulmonary cystic malformations, dental and ophthalmogic complications) compared to those in the non-Proteus group. The cases that met the criteria were more often male, which has implications for hypotheses regarding the etiology and pathophysiology of PS. We also studied the attributes that led authors to conclude the reported patients had PS when we concluded they did not. We found that two of the diagnostic criteria (disproportionate overgrowth and connective tissue nevi) were often misinterpreted. In PS, the abnormal growth is asymmetric, distorting, relentless, and occurred at a faster rate compared to the rest of the body. Furthermore, PS was associated with irregular and disorganized bone, including hyperostoses, hyperproliferation of osteoid with variable calcification, calcified connective tissue, and elongation of long bones with abnormal thinning. In contrast, non-Proteus cases displayed overgrowth that was asymmetric but grew at a rate similar to the growth found in unaffected areas of the body. Also, the overgrowth in non-Proteus cases was associated with normal or enlarged bones together with ballooning of the overlying soft tissues. Taken together, these data show that (1) PS diagnostic criteria sort individuals with asymmetric overgrowth into distinct groups; (2) individuals with PS were more likely to have serious complications; (3) PS affects more males than females; and 4) the published diagnostic criteria are useful for clinical care and research. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.