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Objective: To compare patients' perceptions and preferences of two different versions of informed consent documents., Methods: Patients eligible for a trial of palliative chemotherapy for lung cancer (N = 22) were randomly assigned to receive either an original consent document or a shortened version written for the present study. Semi-structured interviews were conducted after the patients had read the consent documents. The interviews were transcribed verbatim and analysed using qualitative content analysis., Results: Few differences between the two groups were found with respect to patients' assessment of the amount of content and the most important information in the documents. Information about disease and treatment seemed to be of most interest for the patients, while information about research aspects of the study such as financing, confidentiality and publishing (formalities) was judged to be of lesser relevance. Two patients who read the original document indicated that they treated the formalities as secondary., Conclusion: Patients seemed to pay little attention to the research aspects, and thus risked to misunderstand the main point of the consent document., Practice Implications: The structure of consent documents should clarify for the readers that they are asked to take part in research, and that participation is voluntary.

The study examined the family environment and perceived social support of 33 parents with a child diagnosed with Asperger syndrome and 43 parents with a child with learning disability, which were compared to 45 parents of children without disabilities as a control group. Parents completed the Family Environment Scale and Social Support Scale questionnaires. The comparison revealed significant differences for expressiveness and family system organization and for social support. Parents with an Asperger child perceived their family's expressive feelings as lower and the family organization as higher, and perceived their friendships and other support as lower than the other groups of parent. Parents of the control group reported the highest family support. The study highlighted the need for additional social support for parents with a child with special needs, and accentuated the importance of developing awareness and intervention programs to facilitate parents' coping abilities and their family interactions.

Mossy cells are the major class of excitatory neurons in the dentate hilus. Although mossy cells are involved in a range of physiological and pathological conditions, very little is known about their ontogeny. To gain insight into this issue, we first determined the developmental stage at which mossy cells can be reliably identified with the molecular markers calretinin and GluR2/3 and found that hilar mossy cells were first identifiable around the end of the 1st postnatal week. Birthdating studies combined with staining for these markers revealed that the appearance of mossy cells coincided with the first wave of dentate granule cell production during mid-gestation. Since mossy cells are born as the first granule cells are produced and it is believed that mossy cells originate from the neuroepithelium adjacent to the dentate progenitor zone, we examined to what extent the development of mossy cells is controlled by the same molecular pathways as that of granule cells. To do this, we analyzed the production of mossy cells in Lef1 and NeuroD mutant animals, in which granule cell production is disrupted during precursor proliferation or neuronal differentiation, respectively. The production of mossy cells was almost entirely lost in both mutants. Collectively, these data suggests that hilar mossy cells, unlike CA subfield pyramidal cells, are influenced by many of the same developmental cues as dentate granule cells., (Copyright 2007 S. Karger AG, Basel.)

Previous studies have demonstrated that stromal cell-derived factor 1 (SDF-1) is crucial for early dentate development; however, the mouse mutants for this chemokine and its only receptor, CXCR4, are neonatally lethal, making conclusions about the role of these molecules in postnatal development difficult to sustain. Previous expression analyses have used single labeling, but the distribution of CXCR4 is complex and to determine the cell types expressing CXCR4 requires multiple marker labeling. In this study, we examined the distribution of SDF-1 and CXCR4 mRNAs during the first postnatal weeks, combining these markers with several other cell-type-specific markers. We found that SDF-1 has three sites of expression: (1) continuation of prenatal expression in the meninges; (2) expression in Cajal-Retzius cells occupying the molecular layer of the upper and lower blades of the dentate, and (3) the maturing dentate granule neurons themselves. The timing of expression in these three sites corresponds to alterations in the distribution of the primary cell types expressing CXCR4 during the same periods, notably the expression of CXCR4 in radial-glial-like GFAP-expressing dentate precursors and immature dentate granule neurons. Taken together, our data suggest potential ongoing roles for SDF-1/CXCR4 signaling in the dentate gyrus during the early postnatal period that will be tested in the future with more precise genetic approaches.

Normal brain development requires a series of highly complex and interrelated steps. This process presents many opportunities for errors to occur, which could result in developmental defects in the brain, clinically referred to as malformations of cortical development. The marginal zone and Cajal-Retzius cells are key players in cortical development and are established early, yet there is little understanding of the factors resulting in the disruption of the marginal zone in many types of cortical malformation syndromes. We showed previously that treatment with methylazoxymethanol in rats causes marginal zone dysplasia with displacement of Cajal-Retzius cells to deeper cortical layers. Here we establish that loss of activity of the chemokine stromal-derived factor-1 (SDF1) (CXCL12), which is expressed by the leptomeninges, is necessary and sufficient to cause marginal zone disorganization in this widely used teratogenic animal model. We also found that mice with mutations in the main receptor for SDF1 (CXCR4) have Cajal-Retzius cells displaced to deeper cortical layers. Furthermore, by inhibiting SDF1 signaling in utero by intraventricular injection of a receptor antagonist, we establish that SDF1 signaling is required for the maintenance of Cajal-Retzius cell position in the marginal zone during normal cortical development. Our data imply that cortical layering is not a static process, but rather requires input from locally produced molecular cues for maintenance, and that complex syndromes of cortical malformation as a result of environmental insults may still be amenable to explanation by interruption of specific molecular signaling pathways.

Growth deficits associated with lead exposure might be ameliorated by chelation. We examined the effect of succimer on growth in 780 children 12-33 months old who had blood lead levels of 20-44 microg/dL and were randomized to receive up to three 26-day courses of succimer or placebo in a multicenter, double-blind trial. The difference in changes in weight and height between succimer and placebo groups at 1-34 months was calculated by fitting cubic splines. The difference in height change in children on succimer compared with placebo was -0.27 cm [95% confidence interval (95% CI), -0.42 to -0.11] from baseline to 9 months, when 99% of children had completed treatment, and -0.43 cm (95% CI, -0.77 to -0.09) during 34 months of follow-up. Similar differences in weight gain were not statistically significant. Although succimer lowers blood lead in moderately lead-poisoned children, it does not have a beneficial effect on growth and may have an adverse effect.

Objective: Establish the epidemiological characteristics and urinary toxicological profiles of a population of cocaine addicts under police custody., Method: A series of 60 cocaine addicts consulting the medico-legal emergency unit of the Hôtel-Dieu hospital in Paris was studied prospectively on the following elements: clinical characteristics, method of cocaine administration and association with other licit or illicit substances. Urinary toxicological analysis, using immuno-chemistry and chromatography linked to a mass spectrometer was systematically proposed to each patient., Results: Half of the 17 to 26 year-old patients declared having consumed cocaine for the past 2 to 5 years. Inhalation of the vapours and the intravenous route were used more than the cigarette or nasal route. The majority of 26 to 35 year-olds were multi-drug addicted, generally associating cocaine, heroine and tobacco. Analysis of the urine provided an objective assessment of the cocaine consumption of these persons under police custody in Paris., Conclusion: Screening for urinary toxicity gives better knowledge on the consumption of addictive products by the person in whom urine was sampled. This study was conducted in cocaine addicts under police custody, and for the majority were social misfits. In this population, the consumption of crack by inhalation predominated.

During the past 2 decades, the proportion of US children who have blood lead concentrations of 10 microg/dL or higher declined by over 80% after the elimination of leaded gasoline and lead solder from canned foods, and a ban on leaded paint used in housing and other consumer products. Fatalities and symptomatic lead poisoning are now rare. Residential lead hazards, which are exceedingly difficult to control, are currently the major source of lead intake for children. Undue lead exposure has retreated into 2 major risk groups; impoverished children who live in older, poorly maintained rental housing and more affluent children who live in older housing undergoing renovation. Despite the dramatic decline in children's blood lead levels, lead toxicity remains epidemic among impoverished children who live in older rental housing, especially those who live in the northeastern and midwestern regions of the United States. There are increasing data linking lead exposure with other systemic effects including delinquency, dental caries, and learning problems. Moreover, there is evidence indicating that there is no discernible threshold for lead-associated cognitive deficits. Thus, it is increasingly important to shift our efforts toward the primary prevention of childhood lead exposure from residential hazards. This article reviews the epidemiology and control of childhood lead exposure, focusing especially on steps necessary to shift toward primary prevention.

Objective: To assess the problems eventually created by fingerprinting for genetic identification of suspected sexual aggressors., Method: An opinion poll was conducted among 13 practitioners (8 forensic experts and 5 biologists) using a list of 20 questions., Results: Ten practitioners agreed that there were ethical problems in fingerprinting, and 6 of the 13 physicians surveyed claimed that fingerprinting was distressful for the suspect., Comments: The ethical problems most frequently encountered were the presence of a third party during fingerprinting, the practitioners' lack of information at to the test's future use, the suspect's refusal to undergo such a test and the suspect's lack of information on the subsequent computerized treatment of the fingerprint, to enhance a national genetic data base for example, and the length of time during which the fingerprint is stored.

The application of handcuffs may result in compression neuropathies at the wrist. The frequency of these complications is unknown. Twelve of 190 (6.3%) consecutive subjects kept in police custody presented distal neurological symptoms possibly related to handcuff application. The duration of handcuffing was significantly longer in patients with neurological symptoms than in patients without neurological symptoms (mean +/- SD: 3.7+/-5.2 h vs. 1.8+/-2.6 h, P = 0.02). A long duration of handcuff application and, possibly, the existence of somnolence or acute alcohol intoxication could be predisposing factors to handcuff neuropathy. A prospective study of clinical and electrophysiological detection and follow up is needed.

Context: Residential exposures are recognized risk factors for asthma, but the relative contribution of specific indoor allergens and their overall contribution to asthma among older children and adolescents in the United States are unknown., Objective: To estimate the relative contributions, population-attributable risks, and costs of residential risk factors for doctor-diagnosed asthma. Design. Nationally representative, cross-sectional survey conducted from 1988 to 1994., Setting and Participants: A total of 5384 children who were 6 to 16 years old and participated in the National Health and Nutrition Examination Survey III, a survey of the health and nutritional status of children and adults in the United States., Main Outcome Measure: Doctor-diagnosed asthma, as reported by the parent., Results: Five hundred three of 5384 children and adolescents (11.4%) had doctor-diagnosed asthma. After adjusting for age, gender, race, urban status, region of country, educational attainment of the head of household, and poverty, predictors of doctor-diagnosed asthma included a history of allergy to a pet (odds ratio [OR: 2.4; 95% confidence interval [CI]: 1.7, 3.3), presence of a pet in the household (OR: 1.5; 95% CI: 1.1, 2.1), and immediate hypersensitivity to dust mite (OR: 1.5; 95% CI: 1.05, 2.0), Alternaria (OR: 1.9; 95% CI: 1.3, 2.8), and cockroach allergens (OR: 1.4; CI: 1.04, 1.9). Family history of atopy (OR: 1.7; 95% CI: 1.1, 2.7) and diagnosis of allergic rhinitis (OR: 2.1; CI: 1.1, 3.7) were also predictors for asthma. The population-attributable risk of having 1 or more residential exposures associated with doctor-diagnosed asthma was 44.4% (95% CI: 29-60), or an estimated 2 million excess cases. The attributable cost of asthma resulting from residential exposures was $405 million (95% CI: $264-$547 million) annually., Conclusions: The elimination of identified residential exposures, if causally associated with asthma, would result in a 44% decline in doctor-diagnosed asthma among older children and adolescents in the United States.

Background: The pathogenesis of HIV-1-related cardiomyopathy is poorly understood, but HIV-1 has been detected in cardiomyocytes. Whether HIV-1 penetrates into the myocardium by infection of coronary artery endothelial cells (CAEC) or using transcellular or paracellular routes across CAEC has not been resolved., Materials and Methods: A model of the CAEC barrier was constructed with primary CAEC (derived from human coronary vessels). Polymerase chain reaction (PCR) assay, infectious assay, and immunofluorescence were employed to show abortive nature of HIV-1 infection of CAEC. Tight junction (TJ) and cell adhesion proteins were visualized by immunofluorescence. The time course of HIV-1 invasion was measured by HIV-1 RNA assay. Inulin permeability assay determined paracellular leakage. Transmission electron microscopy demonstrated virus-induced endothelial vacuolization., Results: Despite a strong display on CAEC of CXCR4 and a lesser expression of CCR3 and CCR5, HIV-1 did not productively replicate in CAEC, as shown by infectious assay, immunofluorescence, and electron microscopy. HIV-1 infection of CAEC was abortive with minimal reverse transcription of strong stop DNA and pol but not full-length or two LTR DNA circles. Upon infection of the model with 1 million RNA copies of HIV-1JR-FL, virus penetration 2 hr postinfection (PI) was negligible but increased by 1,750% 24 hr PI. The paracellular permeability increased during this period by only 25%. Neither AOP-RANTES nor v-MIPII significantly reduced HIV-1JR-FL invasion. Virus infection did not alter the integral TJ protein occludin and the TJ-associated protein ZO-1. HIV-1 exposed CAEC and brain microvascular endothelial cells (BMVEC) developed extensive cytoplasmic vacuolization with retroviral-like particles in the vacuoles., Conclusions: The endothelium is not an impenetrable barrier to HIV-1. The virus opens a transcellular route across coronary and brain endothelia in cytoplasmic vacuoles.

Optic neuropathy in uremia is rare. Although the consequences of optic neuropathy-blindness or substantial loss of vision-are devastating, only a few cases have been reported by way of single case reports and case series studies. The reported patients are heterogeneous with regard to the cause of neuropathy. We report the case of a patient with uremic optic neuropathy and summarize the other cases reported in the literature so far. Based on the data available from these reports, we propose a classification system, which includes nonischemic neurotoxic uremic optic neuropathy; ischemic optic neuropathy, more specifically anterior ischemic optic neuropathy; and optic neuropathy as a result of drug side effects, benign intracranial hypertension, and optic neuritis. The immediate institution of dialysis and corticosteroid therapy and correction of anemia and relative hypotension can optimize the chances of visual recovery for these patients. Close collaboration among nephrologists, ophthalmologists, and neurologists is important in this interdisciplinary emergency.

This report of a case of symptomatic lead poisoning in infancy reinforces the need for continued vigilance in screening and the application of effective therapies to prevent serious physiologic, neurocognitive, and behavioral sequelae. Furthermore, this case illustrates the efficacy of repeated courses of outpatient succimer therapy in limiting a rebound in blood lead concentrations.

In most cases, extensive cerebral venous thrombosis present themselves with a severe clinical outcome and poor prognosis. We present the case of a 59-years-old patient with a slight rather unrevealing symptoms but suffering from a cerebral thrombosis impacting on both superficial and deep venous system. The etiologic assessment revealed activated protein C resistance. Clinical evolution under systemic anticoagulation was prompt, with complete repermeabilization of the various venous structures.

Background: Chemokine receptors on leukocytes play a key role in inflammation and HIV-1 infection. Chemokine receptors on endothelia may serve an important role in HIV-1 tissue invasion and angiogenesis., Materials and Methods: The expression of chemokine receptors in human brain microvascular endothelial cells (BMVEC) and coronary artery endothelial cells (CAEC) in vitro and cryostat sections of the heart tissue was determined by light and confocal microscopy and flow cytometry with monoclonal antibodies. Chemotaxis of endothelia by CC chemokines was evaluated in a transmigration assay., Results: In BMVEC, the chemokine receptors CCR3 and CXCR4 showed the strongest expression. CXCR4 was localized by confocal microscopy to both the cytoplasm and the plasma membrane of BMVEC. In CAEC, CXCR4 demonstrated a strong expression with predominantly periplasmic localization. CCR5 expression was detected both in BMVEC and CAEC but at a lower level. Human umbilical cord endothelial cells (HUVEC) expressed strongly CXCR4 but only weakly CCR3 and CCR5. Two additional CC chemokines, CCR2A and CCR4, were detected in BMVEC and CAEC by immunostaining. Immunocytochemistry of the heart tissues with monoclonal antibodies revealed a high expression of CXCR4 and CCR2A and a low expression of CCR3 and CCR5 on coronary vessel endothelia. Coronary endothelia showed in vitro a strong chemotactic response to the CC chemokines RANTES, MIP-1alpha, and MIP-1beta., Conclusions: The endothelia isolated from the brain display strongly both the CCR3 and CXCR4 HIV-1 coreceptors, whereas the coronary endothelia express strongly only the CXCR4 coreceptor. CCR5 is expressed at a lower level in both endothelia. The differential display of CCR3 on the brain and coronary endothelia could be significant with respect to the differential susceptibility of the heart and the brain to HIV-1 invasion. In addition, CCR2A is strongly expressed in the heart endothelium. All of the above chemokine receptors could play a role in endothelial migration and repair.

Purpose: To evaluate the efficacy of foraminal steroid injections performed under CT guidance for the management of radicular pain., Methods: Periganglionic infiltrations were performed in 160 patients with radicular pain refractory to medical treatment. Imaging showed either degenerative foraminal stenosis, herniated disk or postsurgical fibrosis., Results: 102 patients (63.8%) had significant pain reduction. Pain relief was lasting in 68 (66.6%). CT showed the position of the needle tip, as well as the diffusion of the therapeutic compounds., Conclusion: We consider that CT-guided periganglionic steroid injections should be an integral part of the management strategy for radicular pain resistant to medical treatment.

We compared the iron status between children 11 to 33 months old with confirmed blood lead levels of 20 to 44 microg/dL and demographically similar children with blood lead levels of <10 microg/dL. There were no differences. Laboratory investigation or empirical treatment for iron deficiency is not justified on the basis of moderately elevated blood lead levels alone.

Leukocyte infiltration of cerebral vessels in cocaine-associated vasculopathy suggests that cocaine may enhance leukocyte migration. We have investigated cocaine's effects on leukocyte adhesion in human brain microvascular endothelial cell (BMVEC) cultures and monocyte migration in an in vitro blood-brain barrier (BBB) model constructed with BMVEC and astrocytes. Cocaine (10(-5) to 10(-9) M) enhanced adhesion of monocytes and neutrophils to BMVEC. In the BBB model, cocaine (10(-4) to 10(-8) M) enhanced monocyte transmigration. Cocaine increased expression of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1, CD54), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1) on BMVEC. The peak effect on ICAM-1 expression was between 6 and 18 h after treatment. ICAM-1 was increased by cocaine in BMVEC, but not in human umbilical vein endothelial cells, and the enhancement was greater in a coculture of BMVEC with monocytes. ICAM-1 expression was enhanced by a transcriptional mechanism. Polymyxin B inhibited up-regulation of adhesion molecules by LPS but not by cocaine. In LPS-activated BMVEC/monocyte coculture, cocaine increased secretion of tumor necrosis factor-alpha and interleukin-6. Taken together, these findings indicate that cocaine enhances leukocyte migration across the cerebral vessel wall, in particular under inflammatory conditions, but the effects are variable in different individuals. Cocaine's effects are exerted through a cascade of augmented expression of inflammatory cytokines and endothelial adhesion molecules. These could underlie the cerebrovascular complications of cocaine abuse.

The effects of cocaine infusion (40 mg) on interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) cytokine secretion were examined in 15 cocaine-dependent subjects. Pre- and postcocaine infusion peripheral blood mononuclear cells (PBMC), stimulated with phytohemagglutinin A, were cultured for 48 h and the cytokines in the supernatant measured by enzyme-linked immunosorbent assay. Cocaine infusion, but not saline infusion, increased IFN-gamma secretion and decreased IL-10 secretion, while, in PBMC collected simultaneously from control subjects, secretion of these cytokines was unaltered. Baseline IFN-gamma levels were lower and IL-10 levels higher in addicted subjects compared to those in control subjects. White blood cell and lymphocyte number and CD4(+) and CD8(+) counts were all increased following cocaine infusion. In vitro cocaine treatment of PBMC from addicted subjects suppressed both IL-10 and IFN-gamma secretion. These data suggest that acute cocaine administration, via both central and peripheral effects, may enhance Th1-type immune responses and inhibit Th2-type responses., (Copyright 1998 Academic Press.)

Postural balance testing was used as a measure of the effect of therapy on a 9 year old boy with high lead levels. Following therapy with CaEDTA and succimer, the patient's postural sway responses were comparable to a low-lead (< 10 micrograms/dL) comparison group for 3 out of 4 tests which rely relatively less on the higher centers for balance. This improvement in postural balance may be attributable to the combined influence of pharmacologic and age associated maturational effects. This case study provides suggestive evidence that while chelation therapy can reduce PbB levels quickly, it can also modify gross neuromotor function manifested by postural balance characteristics.

Lipid adhesion forces can be measured using several experimental techniques, but none of these techniques provide insight on the atomic level. Therefore, we performed extensive nonequilibrium molecular dynamics simulations of a phospholipid membrane in the liquid-crystalline phase out of which individual lipid molecules were pulled. In our method, as an idealization of the experimental setups, we have simply attached a harmonic spring to one of the lipid headgroup atoms. Upon retraction of the spring, the force needed to drag the lipid out of the membrane is recorded. By simulating different retraction rates, we were able to investigate the high pull rate part of the dynamical spectrum of lipid adhesion forces. We find that the adhesion force increases along the unbinding path, until the point of rupture is reached. The maximum value of the adhesion force, the rupture force, decreases as the pull rate becomes slower, and eventually enters a friction-dominated regime. The computed bond lengths depend on the rate of rupture, and show some scatter due to the nonequilibrium nature of the experiment. On average, the bond length increases from approximately 1.7 nm to 2.3 nm as the rates go down. Conformational analyses elucidate the detailed mechanism of lipid-membrane bond rupture. We present results of over 15 ns of membrane simulations. Implications for the interpretation and understanding of experimental rupture data are discussed.

Most for polyneuropathies present in a uniform, distally accentuated, rather symmetrical pattern, although asymmetric or multifocal distributions occur. The main feature of diagnosis is the history of development and the neurological clinical examination. Neurophysiologic studies, mainly nerve conduction studies (motor and sensory), reflex studies and electromyography are very accurate, but unspecific tools in order to establish the diagnosis of polyneuropathies, define special electrophysiologic features and can also reveal undetected (subclinical) lesions. For clinical purposes most neuropathies can be divided according the nerve conduction studies in axonal, demyelinating and mixed types. In recent years additional electrophysiological features as conduction block have appeared and are still under discussion. The etiology of polyneuropathy has to be determined in each patient with scrutinity. Additionally to general diseases (e.g. diabetes), common toxins (e.g. alcohol), concurrent medication (e.g. some cytostatic drugs) also immunologic (e.g. vasculitis) and hereditary factors have to be considered. A nerve biopsy is only indicated after a thorough consideration of electrophysiology and ancilliary findings. This applies in particular to hereditary neuropathies, where genetic testing has become a highly reliable test replacing biopsy.

Molecular dynamics simulations on bacteriorhodopsin were performed starting from a conformation based on electron cryomicroscopy studies [Henderson, R., et al. (1990) J. Mol. Biol. 213, 899-929]. We examined the proton release channel in different intermediates of the bacteriorhodopsin photocycle. In the simulations of the ground state, two stable sets of conformations were observed differing in the distance of the guanidinium group of Arg82 to the Schiff base. The set of conformations in which Arg82 is located closer to the Schiff base has a lower potential energy and agrees better with experimental data than the other set. With both sets, we performed a series of simulations in which the chromophore was isomerized to different states using purposive and nonpurposive methods. The energetic consideration of the different states argues for the location of the guanidinium group of Arg82 close to the Schiff base. The results also show that no C13-C14, C14-C15 dicis conformation of the retinal occurs in the K/L-intermediate of the photocycle instead supporting the occurrence of C13-C14 cis in these intermediates. In a last series of simulations, we modeled the M-intermediate of the bacteriorhodopsin photocycle. Again, comparison to different experimental data indicates that Arg82 points toward the Schiff base. We conclude that the guanidinium group of Arg82 is located close to the Schiff base at a distance of approximately 4.5 A and stays there at least up to the M-intermediate of the photocycle.

Objective: This study involved 35 patients who claimed to have been drugged before being robbed or raped, despite urine negative toxicologic screening by immunoenzymatic methods. The urines were frozen for further investigations, including enzymatic hydrolysis of urinary conjugates, liquid-solid extraction and, finally, immunoenzymatic screening of concentrated urine extract., Methods: Urine benzodiazepines were analyzed by immunoenzymatic assay before and after enzymatic hydrolysis combined with extraction., Results: On direct immunoenzymatic screening, 17 of the 35 urine samples were benzodiazepine positive. Enrichment of preserved specimens improved the detection threshold from 200 ng/mL to 50 ng/mL and 10 of the 18 negative urines became positive., Conclusion: This method allowed us to demonstrate the benzodiazepines in half of previously negative urine samples. Benzodiazepine screening is particularly problematic because of low dosage, rapid elimination, failure to detect conjugated metabolites by immunoenzymatic reagents and high threshold of sensitivity for certain substances.

Molecular dynamics simulations on bacteriorhodopsin were performed starting from the model structure described by Henderson et al. The simulations were gradually improved by first treating a monomer in vacuum and then adding further monomers, lipids, and water to finally simulate a unit cell of the hexagonal lattice of the purple membrane containing a trimer and lipids and water on both sides. During all simulations, the protein structure moved away from the model structure to reach a root-mean-square (r.m.s.) deviation of 2 to 3 A. In the simulations with the trimer, the structures of the three monomers differed by about the same amount and averaging over them led to an average structure with a considerably smaller r.m.s. deviation. The best average structure obtained had an r.m.s. deviation from the model structure of 1.3 A. Fluctuations of the protein, the lipids, and water were analyzed in detail. As expected, the membrane-spanning helices of the protein fluctuate less than the peripheral loops. Unexpected, however, was the finding that the fluctuations of the protein are asymmetric with respect to the midplane of the membrane. The fluctuations of the loops and the ends of the helices on the inner side of the membrane are much stronger than on the outer side. This asymmetry is also reflected by the fluctuations for the lipids, the lipids of the inner leaflet fluctuating more strongly than those of the outer leaflet. The asymmetry was observed only in the presence of water on both sides of the membrane. On the average, nine water molecules were found inside the protein, most of them undergoing exchange with external water.

A 73 year old male who had been prescribed fenofibrate for years developed a slightly asymmetric paraparesis of both lower extremities. CPK values rose to 9800 U/l, EMG of the quadriceps femoris muscle was myopathic. Muscle biopsy revealed a necrotic myopathy. Discontinuation of fenofibrate induced a rapid decline of CPK values, followed by a slower remission of muscular symptoms and persisting pseudo-myotonic discharges in EMG. The spectrum of neuromuscular side effects of cholesterol lowering agents, consisting of myalgia, cramps and reversible CPK elevation, is discussed. Only rarely necrotic myopathies have been described.

The relationship between asymptomatic lead exposure and subtle deficits in intellectual attainment has been relatively well established by modern studies. However, neuromotor performance has rarely been the focus of these investigations. It was postulated that motor developmental outcomes may be more sensitive indicators of lead's adverse effects on the central nervous system as they are probably less confounded with social factors than cognitive and academic outcomes. A comprehensive neuromotor assessment battery was administered to 245 six-year-old urban inner-city children enrolled in the Cincinnati Lead Study. These children have been followed since birth with quarterly assessments of blood lead concentrations, medical status, and neurobehavioral development. Prior to covariate adjustment, neonatal, but not prenatal blood lead levels were associated with poorer scores on assessments of bilateral coordination, upper-limb speed and dexterity, and a composite index of fine-motor coordination. Averaged postnatal blood lead levels were also associated with lower scores on the aforementioned subtests as well as a measure of visual-motor control. Following statistical adjustment for covariates, neonatal blood lead levels were associated with poorer performance on a measure of upper-limb speed and dexterity and the fine-motor composite. Postnatal blood lead levels remained significantly associated with poorer scores on measures of bilateral coordination, visual-motor control, upper-limb speed and dexterity, and the fine-motor composite. Low to moderate lead exposure is associated with moderate deficits in gross and especially fine-motor developmental status. Results of this study provide support for recent initiatives to reduce the exposure of children to sources of environmental lead.

This analysis examined the relationship between lead exposure as registered in whole blood (PbB) and the central auditory processing abilities and cognitive developmental status of the Cincinnati cohort (N = 259) at age 5 years. Although the effects were small, higher prenatal, neonatal, and postnatal PbB levels were associated with poorer central auditory processing abilities on the Filtered Word Subtest of the SCAN (a screening test for auditory processing disorders). Higher postnatal PbB levels were associated with poorer performance on all cognitive developmental subscales of the Kaufman Assessment Battery for Children (K-ABC). However, following adjustment for measures of the home environment and maternal intelligence, few statistically or near statistically significant associations remained. Our findings are discussed in the context of the related issues of confounding and the detection of weak associations in high risk populations.

This report is a follow-up of an earlier study of the effects of low to moderate prenatal and postnatal lead exposure on children's growth in stature. Two hundred thirty-five subjects were assessed every 3 months for lead exposure (blood lead level) and stature (recumbent length) up to 33 months of age. Fetal lead exposure was indexed by maternal blood lead level during pregnancy. The adverse effects of lead on growth during the first year of life were reported previously. This analysis covers essentially the second and third years of life. The results indicate that mean blood lead level during this period was negatively associated with attained height at 33 months of age (P = .002). This association was, however, evidenced only among those children who had mean blood lead levels greater than the cohort median (greater than or equal to 10.77 micrograms/dL) during the 3- to 15-month interval. The results also suggest that the effect of lead exposure (both in utero as well as during the first year of life) are transient provided that subsequent exposure to lead is not excessive. It appears that maintaining an average blood lead level of 25 micrograms/dL or more during the second and third year of life was detrimental to the child's attained stature at 33 months of age. Approximately 15% of this cohort experienced these levels of lead exposure. Continued follow-up of this cohort will reveal whether these lead-related deficits persist and whether they continue to be dependent on the level of exposure in an earlier period.

One hundred five children (49 male, 99 black) with known lead exposure indices from birth and adequate nutrient intake of calcium, phosphorus, and vitamin D were studied at 1 of 3 ages (21, 27, or 33 months) to determine the effects of chronic low to moderate lead exposure on circulating concentrations of vitamin D metabolites and bone mineral content as determined by photon absorptiometry. Univariate multiple regression analyses showed no direct relationship of blood lead levels to vitamin D metabolites or bone mineral content. Structural equation analyses which took into account potential covariates of age, season, race, and sex showed estimated declines in serum concentrations of total calcium (from 9.72 to 9.61 mg/dL), phosphorus (from 5.4 to 4.67 mg/dL), and 25-hydroxyvitamin D (from 27.24 to 25.8 ng/mL) and estimated increases in concentrations of parathyroid hormones (from 73.03 to 83.14 microL Eq/mL), 1,25-dihydroxyvitamin D (from 62.39 to 62.69 pg/mL), and bone mineral content (from 222.66 to 234.91 mg/cm) over the observed range of average lifetime blood lead concentrations (4.76 to 23.61 micrograms/dL, geometric mean 9.74 micrograms/dL). However, the only statistically significant effect of average lifetime blood lead concentration was that for phosphorus, and the multivariate test of the combined effects of lead on these six outcomes was not statistically significant (P = .2). It is concluded that significant alterations in vitamin D metabolism, calcium and phosphorus homeostasis, and bone mineral content are not present in children whose nutritional status is adequate and who experience low to moderate lead exposure.

The purpose of this analysis was to determine if significant associations could be observed between prenatal/postnatal blood lead (PbB) levels and the cognitive development of 258 urban, inner-city children at 4 years of age. These children have been followed since birth with frequent assessments of general health, PbB, and neuropsychological status. The Kaufman Assessment Battery for Children (K-ABC) was administered at approximately 4 years of age. Higher neonatal PbB levels were associated with poorer performance on all K-ABC subscales. However, this inverse association was limited to children from the poorest families. Maternal PbB levels were unrelated to 4-year cognitive status. Few statistically significant associations between postnatal PbB levels and K-ABC scales could be found. However, the results did suggest a weak inverse relationship between postnatal PbB levels and performance on a K-ABC subscale which assesses visual-spatial and visual-motor integration skills. In these results we note both contradiction and accord with previously published prospective studies.

Drug packets are usually detected by ordinary abdominal radiographs, which is of major importance in the apprehension and prosecution of drug body packers, but false negatives may occur. We report the case of a cocaine body packer who had used the prograde route and in whom the initial abdominal plain films were normal. The diagnosis of cocaine body packing was assessed by seldom-described complementary methods of detection, including drug detection in the urine and contrast study of the bowel.

Clinical, immunological, and functional investigations were conducted to study possible specific factors involved in the etiology of asthma in adults. The authors emphasize the frequency of positive skin, radio-immunologic and bronchial provocation tests for domestic pneumallergens in patients with common asthma, even those over 40 years of age. These cases improve in a protected environment and may benefit from immunotherapy. In patients with clinical manifestations suggesting possible occupational etiological factors the same tests can be used to diagnose the presence of a wide variety of vegetable or animal allergens. Tests involving exposing the bronchi to various chemical compounds used during working conditions (antibiotics, plastic precursors, metals, hair preparations) show that there exists a wide variety of causes. Systematic search for etiological factors is essential when investigating asthma in adults.

Fecal lead excretion (PbF) was studied in young children with elevated lead exposure. PbB was generally 40-70 microgram/dl. The children's home environments were classified as to lead-base paint hazard and traffic density. There was a significant correlation between paint hazard classification and PbF but not between traffic density and PbF. There also was a correlation of PbB with paint hazard classification. Long-term fecal collections were instituted using 10 children who lived in high hazard homes and three children with low PbB's, whose PbF's were considered normal. Among the children living in high hazard homes, median fecal lead excretion generally was only moderately elevated. Grossly elevated amounts of led were found only occasionally and only in a few of the children. Movement of two children from a high hazard home to a low hazard home resulted in prompt and substantial reduction in PbF. By contrast, PbB fell only very slowly.

A prospective method was used in this study to assess the effects of fetal lead exposure on neurodevelopmental status in 3- and 6-month old infants. At their first prenatal medical appointments, 305 lower socioeconomic status women residing in predesignated lead-hazardous areas of Cincinnati were recruited. Lead was measured in whole blood in both the mother and fetal-placental unit (prenatal and cord) and the neonate (ten days and 3 months). All blood lead levels were less than 30 micrograms/dL. Infant development was assessed with the Bayley scales at 3 and 6 months of age. Multiple regression analyses which treated perinatal health factors such as birth weight and gestation as confounders indicated an independent, inverse relationship between both prenatal and neonatal blood lead levels and performance on the Bayley Mental Developmental Index at both ages. Male infants and infants from the poorest families appeared to be especially sensitive to these psychoteratogenic influences. Further study using a structural equations approach indicated that neurobehavioral deficits were partly mediated by lead-related reductions in birth weight and gestation.

In world industry and agriculture as a whole, the number of people with asthma and complex pneumopathies related to chemical and organic pollution seems important. Indeed, subjects with an atopic inclination are often the first to be jeoparized. However, it must be stressed that occurrence of asthma in relation with work should always lead to investigate an anomaly in professional hygiene. For other workers this latter eventuality constitutes in the long run a threat of precipitin pneumopathy, chronic bronchitis, pulmonary fibrosis, or even cancer (in the case of nickel). Selection upon hiring is an unsatisfactory measure. The improvement of the atmospheric conditions at work should always be sought for. In some professional asthma cases, we were able to confirm that medication provides efficient protection. This solution, however, seems only slightly satisfactory since the subject is still left in contact with substances which have harmful effects other than asthma. It is therefore important that doctors track down and explore the cases of professional asthma, declaring their existence to social security and work inspection organizations, in order to establish an epidemiological knowledge, regularly updated, which would provide an indispensable basis for any prevention through improvement of working conditions.

One hundred cases of intracorporeal concealment of narcotic drugs were observed over a 6-month period at the medico-judicial emergency centre of the Hotel-Dieu hospital, Paris. Twelve cases concerned dealers who had ingested packs at the time they were arrested. The other subjects had been carrying the drug in their digestive tract, rectum or vagina for transportation. The illicit drugs thus transported were cocaine in 20 cases (ingestion), heroin in 65 cases (ingestion 7, rectal or vaginal cavity 58) and cannabis in 3 cases. Packs for sale being fragile, the dealers were particularly exposed to overdosage. Their management prior to intoxication was the same as that of acute ordinary drug poisoning, i.e. washing out of the stomach. In carriers, the risk of severe poisoning was associated with ingestion. The lack of antidote makes cocaine poisoning particularly dangerous. Surgical extraction is now reserved to cases with intestinal mechanical complications and to those increasingly rarer cases of fragile transportation packs.

The presence of opiates and benzoylecgonine, the major metabolite of cocaine, in the urine was detected by means of enzyme immunoassay in a series of 120 smugglers who had either ingested or inserted into their rectum cocaine or heroin packaged for transportation. There was a striking relation between the presence of drugs in the urine and swallowing of drug-filled bundles (cocaine 49 of 50 cases, heroin 9 of 10). The proportion of positive results was also high in cases of rectal insertion (cocaine 2 of 2, heroin 35 of 58). In 30 cases of cocaine-packet ingestion, serial measurements showed that the accuracy of the test progressively decreased with respect to the detection of residual packets in the body. Drug detection in the urine of suspected body-packers seems to be a useful test, positive results justifying subsequent radiological investigations.