Divalent-selective voltage-independent calcium channels in Lymnaea neurons: permeation properties and inhibition by intracellular magnesium. Calcium channels are tightly regulated. Voltage-gated calcium channels open only in response to depolarization, while voltage-independent calcium channels usually open only in response to specific intracellular or extracellular ligands. Voltage-independent calcium channels have been described in several invertebrate neurons. One difficulty in understanding the function of the neuronal channels is that their regulators are unknown. They open rarely in intact cells but are activated by formation of a cell-free patch, suggesting that some intracellular inhibitor usually keeps them closed. This article provides evidence that intracellular Mg2+ is one important regulator of the voltage-independent calcium channel (HP channel) in neurons of the pond snail Lymnaea stagnalis. Mg2+ (1 mM) rapidly and reversibly inhibited activity of this calcium channel when applied to the intracellular side of cell-free membrane patches. The primary effect of the Mg2+ was to promote long closings of the channel. The mechanism of the intracellular Mg2+ inhibition is distinct from open channel block, a phenomenon seen in a variety of cation channels. Open channel block can also be seen in the HP channels, but only at very positive membrane potentials. Some of the permeability and selectivity characteristics of these channels were also examined. The channels are permeable to Mg2+ and Ca2+ as well as Ba2+. Outward currents carried by monovalent cations can be observed only at very positive membrane potentials, indicating high selectivity for divalent over monovalent cations. The single channel current-voltage relationship is markedly nonlinear, becoming quite shallow near the reversal potential, and hence is qualitatively similar to that seen in many voltage-activated calcium channels.


Heat shock protein expression in vulnerable cells of the rat hippocampus as an indicator of excitation-induced neuronal stress. The inducible 72 kDa heat shock protein (HSP72) has been shown to be protective in non-neuronal cells and neurons in culture, but its function and the control of its expression in the CNS are poorly understood. Although HSP72 is induced in neurons in vivo by neurotoxic compounds that produce seizures and neuronal damage, it is unknown if its expression is a specific response to excitation per se or to "stressful" or potentially injurious excitation, or if it is a marker or mediator of irreversible injury. We have attempted to identify the nature of the stimulus for HSP72 expression by utilizing focal electrical stimulation that can either excite or destroy postsynaptic cells, depending on the duration of afferent stimulation. Previous studies have demonstrated that intermittent stimulation of the main hippocampal afferent pathway for 24 hr evokes synchronous discharges in dentate granule cells but does not injure them. However, the same stimulation irreversibly destroys three of the four cell populations innervated by the granule cells. The three vulnerable populations are the dentate hilar mossy cells, the somatostatin/neuropeptide Y (NPY)-immunoreactive hilar neurons, and the CA3c pyramidal cells. The fourth and relatively resistant population is the GABA-immunoreactive dentate basket cells. In this study, we have localized HSP72 expression immunocytochemically in the hippocampal dentate gyrus in response to nontoxic durations of potentially neurotoxic afferent stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification and developmental expression of a novel low molecular weight neuronal intermediate filament protein expressed in Xenopus laevis. Xenopus laevis is a valuable model system for the study of vertebrate neuroembryogenesis. However, very few well-characterized nervous system-specific molecular markers are available for studies in this organism. We screened a X. laevis adult brain cDNA library using a cDNA probe for mouse low molecular weight neurofilament protein (NF-L) in order to identify neuron-specific intermediate filament proteins. Clones for two distinct neuron-specific intermediate filament proteins were isolated and sequenced. One of these encoded for a Xenopus NF-L (XNF-L) and the other for a novel neuron-specific Xenopus intermediate filament protein (XNIF) that was present earlier and more abundantly than XNF-L during development. XNIF contained a central rod domain with multiple sequence features characteristic of IF proteins. The XNF-L was very similar to mouse NF-L, with a 77% sequence identity in the rod domain and the presence of a polyglutamic acid region in the tail domain, characteristic of type IV neurofilament proteins. In contrast, XNIF showed only 60% identity to mouse NF-L in the rod domain and lacked the glutamic acid-rich sequence in the tail domain. XNIF also had a very low (approximately 38%) sequence identity in the head and tail domains as compared to NF-L and other neurofilament proteins (45% identity to the head domain of alpha-internexin). In the adult frog, XNIF mRNA is detected by Northern blots only within the nervous system and by in situ hybridization histochemistry exclusively in neurons, particularly in the medullary reticular system and spinal cord. Antisera raised against the unique tail region of XNIF detected a single distinct 60 kDa band in Western blots of nervous system cytoskeletal preparations, and this XNIF immunoreactivity was concentrated in axons in the PNS and in small perikarya in the dorsal root ganglion. In contrast, NF-L immunoreactivity was principally in the large perikarya in the dorsal root ganglion. In development, XNIF mRNA appears more abundant than XNF-L mRNA in all premetamorphic stages examined. XNIF mRNA is first detectable at stage 24 (26 hr), whereas stable expression of XNF-L is at stage 35/36 (50 hr). XNIF immunoreactivity is detectable within the cement gland, within many neuronal cell bodies and axon tracts within the developing nervous system, and within all cellular layers of the developing retina. The availability of these two distinct neuron-specific intermediate filament proteins, with different temporal and spatial expression patterns, should provide new markers as well as targets for functional perturbation in the developing X. laevis nervous system.


Formation of specific afferent connections in organotypic slice cultures from rat visual cortex cocultured with lateral geniculate nucleus. The development of the cerebral cortex involves the specification of intrinsic circuitry and extrinsic connections, the pattern of inputs and outputs. To investigate the development of a major afferent input to the cortex, we studied the formation of thalamocortical connections in an organotypic culture system. Slices from the lateral thalamus of young rats were cocultured with slices from the visual cortex. Thalamocortical projections in vitro were examined anatomically with fluorescent dyes and physiologically with electrophysiological and optical recording techniques. Axons emerged from thalamic explants radially in all directions. The outgrowth of thalamic fibers and the course of the axonal trajectories were not influenced by the presence of the cocultured cortex. Only those thalamic axons that happened to grow toward the cortical slices invaded their target tissue. Thalamocortical projection cell in vitro had the characteristic morphology of thalamic relay neurons. Cells with the morphology of interneurons were present in thalamic explants, but these neurons did not project to the cocultured cortex. Thalamocortical axons in vitro terminated in their appropriate cortical target layer, formed axonal arbors, and made functional synaptic contacts. Such specific connections between thalamic neurons and their cortical target cells were established regardless of whether thalamocortical axons invaded the cortex from the white matter side or from the pial surface. These results suggest that thalamic projection neurons have an innate mechanism that allows them to recognize their cortical target cells. Thus, intrinsic factors play a significant role in the laminar specification of cortical connections during development.


Phosphorylation of DARPP-32 and protein phosphatase inhibitor-1 in rat choroid plexus: regulation by factors other than dopamine. The molecular mechanisms underlying regulation of fluid production by secretory epithelia such as the choroid plexus are poorly understood. Two cAMP-regulated inhibitors of protein phosphatase-1, inhibitor-1 (I1) and a dopamine- and cAMP-regulated phosphoprotein, M(r) = 32,000 (DARPP-32), are enriched in the choroid plexus. We show here that these two phosphoproteins are colocalized in choroid plexus epithelial cells. We have developed a novel method for studying the phosphorylation state of DARPP-32 and I1 in intact cells, using a phosphorylation state-specific monoclonal antibody. Several drugs and hormones that are known to alter fluid secretion and that increase cAMP levels (forskolin, isoproterenol, vasoactive intestinal peptide) or cGMP levels (atrial natriuretic peptide) or that may use additional second messenger pathways (5-HT), increase the phosphorylation of I1 and DARPP-32 in rat choroid plexus. In contrast, dopamine does not alter cAMP and cGMP levels, or I1 and DARPP-32 phosphorylation. Our results indicate that DARPP-32, known to be regulated by dopamine in a number of tissues, can be phosphorylated in response to non-dopaminergic factors, including hormones acting through non-cAMP-dependent pathways. Our results also raise the possibility that inhibition of phosphatase-1, as a result of I1 and DARPP-32 phosphorylation, might be part of a final common pathway in the action of several factors that are known or thought to alter cerebrospinal fluid production.


Synaptic pharmacology of the superior olivary complex studied in mouse brain slice. The synaptic pharmacology of the lateral superior olive (LSO) and medial nucleus of the trapezoid body (MNTB) was examined in a brain slice preparation of the mouse superior olivary complex (SOC). Physiological responses in SOC were elicited by electrical stimulation of the trapezoid body ipsilateral or contralateral to the recording site, and bilateral interactions were investigated by combined ipsilateral and contralateral stimulation. Pharmacological effects were tested by bath application of amino acid agonists and antagonists. Neurons in MNTB were excited by contralateral stimulation and unaffected by ipsilateral stimulation. Excitatory amino acid (EAA) agonists--kainic acid (KA), quisqualic acid (QA), or L-glutamate--caused spontaneous firing at low concentrations and eliminated responses at higher concentrations in MNTB. The EAA agonist NMDA had relatively little effect at comparable concentrations. Stimulus-elicited responses were blocked by non-NMDA antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX) and by the nonspecific EAA antagonist kynurenic acid, but were unaffected by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV). LSO neurons were typically excited by ipsilateral stimulation and inhibited by contralateral stimulation. In LSO, KA, QA, and L-glutamate caused spontaneous firing at low concentrations and eliminated responses at higher concentrations, and NMDA had relatively little effect. Excitatory responses in the vast majority of LSO neurons were blocked by CNQX, DNQX, or kynurenic acid. Some responses were also blocked by APV. LSO neurons were affected by glycine, and contralateral inhibition in LSO was completely blocked by strychnine. NMDA also blocked inhibition in LSO. These results indicate that excitation of both MNTB and LSO neurons is mediated primarily by an EAA neurotransmitter through non-NMDA receptors and that contralateral inhibition of LSO cells is mediated through strychnine-dependent glycine receptors. NMDA receptors may play a role in binaural processing by modulating contralateral inhibitory input to LSO.


Comparative migration and development of astroglial and oligodendroglial cell populations from a brain xenograft. In previous studies of brain transplantation, the fate of the implanted glial cells has been investigated separately; that is, the interest has been focused either on the astroglia or on the oligodendroglia. However, the two populations of implanted glial cells may interact with each other, for example by secreting species-specific factors or by inducing reactions by the host. We have used two different models of brain transplantation: one that allows the identification of the implanted astrocytes, and another that allows the identification of the implanted oligodendroglia. The present model is a combination of both; it consists of the grafting of embryonic rabbit brain fragments into the brains of neonatal Shiverer mice. The myelin made by the implanted oligodendrocytes is identified by anti-myelin basic protein immunohistochemistry. The implanted astrocytes are identified by a monoclonal antibody that combines with rabbit but not with mouse glial fibrillary acidic protein. This study shows that although they use the same major routes of migration, both populations of glial cells tend to move differently. They demonstrate areas of common settlement but also areas where only one population of implanted glia is present. From the site of implantation in the dorsal striatum, the major routes of migration are the corpus callosum, the white matter fascicles in the striatum, and the internal capsule. After a delay of 6 weeks, no significant prevalence of one population of implanted glial cells over the other was observed.


Polysialic acid is required for optimal growth of axons on a neuronal substrate. Formation of axonal pathways involves a variety of molecules that influence cell-cell interactions. The polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) is present on neuronal surfaces during process outgrowth. Our studies reveal that the removal of PSA causes a decrease in the rate of elongation of retinal cell processes on a substrate of neuronal membranes derived from chick tectum. This effect was partially reversed by antibodies against the L1 adhesion molecule, but not by antibodies against NCAM, N-cadherin, or beta 1-integrins. This predominant effect of PSA on L1 was also observed in short-term, cell-cell adhesion assays, suggesting that PSA promotes optimal outgrowth on neuronal substrates by limiting the consequences of L1-mediated adhesion.


Differential imaging of ocular dominance and orientation selectivity in monkey striate cortex. Differential images of ocular dominance, acquired by comparing responses to the two eyes, reveal dark and light bands where cortical cells are dominated by the right and left eyes. These include most (but not all) histochemically stained cytochrome oxidase blobs in their centers. Differential images of orientation, acquired by comparing responses to orthogonal orientations, reveal dark and light bands that are reminiscent of the "orientation columns" reported earlier, on the basis of 2-deoxyglucose (2DG) autoradiograms (Hubel et al., 1978). However, they are shorter and more fragmented because they do not include regions lacking selectivity for orientation. Even though these "bands" derive from orientation-selective areas, comparisons with differential images of other orientations reveal that regions along their centers prefer different orientations. Hence, the orientation preferences inferred from "bands" in single differential images, or single 2DG autoradiograms, are not necessarily incorrect. Interactions between ocular dominance and orientation were investigated by comparing differential images of orientation obtained with binocular and monocular stimulation, as well as by comparing differential images of ocular dominance obtained with different orientations. In both cases, the elicited interactions were minimal, indicating a remarkable and unexpected independence that subsequent experiments revealed arises, at least in part, from a lateral segregation of regions most selective for one eye and regions most selective for one orientation, in the centers and edges of ocular dominance columns. Since this can also be viewed as a lateral correlation between binocularity and orientation selectivity, it fits with the simultaneous emergence of these properties in layers receiving input from layer 4c, and suggests that each of these properties requires the other.


Regulation of neuronal growth cone filopodia by intracellular calcium. Filopodia have been regarded as the sensory extensions of neuronal growth cones. As such, filopodia assay distant environments and are important for directing growth cones toward their targets. Since the territory encountered by a growth cone depends on the area spanned by the filopodia, changes in filopodial length or number result in the "exploration" of different-sized regions of the environment. The present study tests the potential regulatory role of intracellular calcium levels ([Ca2+]i) on filopodial morphology in identified neurons from the snail Helisoma. Experimentally evoked changes in [Ca2+]i were measured with the fluorescent calcium indicator fura-2 and directly correlated with growth cone filopodial morphology. A rise in [Ca2+]i caused two distinct, concentration-dependent effects separable by their different time courses: within the first 10 min, filopodia underwent significant elongation, while the second phase was characterized by a massive loss of filopodia. Both of these behaviors were increased in a calcium-dependent fashion. The magnitude of both filopodial elongation and filopodial loss correlated well with the transient peak values of [Ca2+]i reached during a given experimental treatment (r less than or equal to 0.98). In addition to the direct effect of the initial transient rise in [Ca2+]i, there is evidence for a form of adaptation of filopodial behavior to sustained calcium levels. A transient change in [Ca2+]i of as little as 30-50 nM reliably altered filopodial morphology. These results indicate that even small changes in intrinsic calcium homeostatic properties or extrinsic signals that alter intracellular calcium levels can act as regulators of the size of the environment sampled by an elongating growth cone.


Sulforhodamine labeling of neural circuits engaged in motor pattern generation in the in vitro turtle brainstem-cerebellum. A fluorescent molecular probe was used in combination with a novel in vitro preparation to study spatial patterns of neural activity associated with motor pattern generation. The in vitro brainstem-cerebellum preparation takes advantage of the turtle's unusual resistance to anoxia to preserve the entire neural network that connects the cerebellum, red nucleus, and reticular formation. This preparation was bathed in a 0.01% solution of sulforhodamine while it was activated unilaterally by electrical stimulation of the dorsal quadrant of the spinal cord for 1 hr. Sulforhodamine is a small, sulfonated, highly charged fluorescent molecule that is taken up by endocytosis. To examine its distribution in the cerebellum and brainstem, coronal sections were prepared and viewed under epifluorescence illumination. Distinctive spatial patterns of labeling were associated with unilateral electrical stimulation of the in vitro network, suggesting that dye uptake was activity dependent. Blockade of uptake with altered magnesium and calcium concentrations indicated that single spike discharge evoked ortho- or antidromically was insufficient to induce dye uptake. Instead, sulforhodamine staining correlated with the presence of burst discharge that was recorded extracellularly from the red nucleus. Blockade of burst discharge with excitatory amino acid receptor antagonists prevented dye uptake in the red nucleus, the lateral cerebellar nucleus, and other structures that are known to be interconnected by recurrent anatomical pathways. These results suggest that sulforhodamine is internalized by intensely active neurons. The spatial distributions of label support the hypothesis that burst discharges in the turtle red nucleus are mediated by excitatory amino acid neurotransmitters and sustained by recurrent excitation in cerebellorubral synaptic pathways. Positive feedback in these recurrent pathways may provide an important driving force for the generation of motor programs that control limb movements.


A comparison of the interaural time sensitivity of neurons in the inferior colliculus and thalamus of the unanesthetized rabbit. The localization of low-frequency sounds (less than 3 kHz) along the azimuth involves comparing the ongoing difference in the time of arrival of a sound at the two ears. Information about interaural time differences (ITDs) is derived from an initial comparison performed in the superior olivary complex. However, little is known about which aspects of this information are transformed as it ascends the brainstem. To address this issue, we compared the ITD sensitivity of neurons in the inferior colliculus (IC) and auditory thalamus, successive stations in the auditory pathway. We found ITD sensitivity in the IC and thalamus to be similar in several respects. At both levels, the large majority of neurons responded maximally to ITDs within the range that a rabbit would normally encounter (+/- 300 microseconds) and preferred ipsilateral delays, delays that would be created by sounds in the contralateral sound field. The range of frequencies over which ITD sensitivity was expressed was also similar in the midbrain and thalamus. Several differences were also apparent. In comparison to IC neurons, neurons in the thalamus responded over more restricted ranges of ITD, responded at lower rates, and, in response to monaural stimulation, showed an increased influence of inhibition. Finally, a greater proportion of thalamic units had characteristic delays corresponding to intermediate discharge rates. The preservation of a bias for ipsilateral delays from IC to thalamus suggests that a representation of contralateral azimuths is present at both levels. Similarities between the two levels suggest that information about ITDs is faithfully transmitted from midbrain to thalamus. Differences in ITD sensitivity, such as the sharper tuning for ITDs, suggest that the thalamus is not a simple relay. Enhanced sensitivity to ITDs should translate to better-defined azimuthal receptive fields, and therefore may be a step toward achieving an optimal representation of azimuth within the auditory pathway.


Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor. Ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF) were tested for effects on sprouting by motor neurons innervating the adult mouse gluteus muscle. Factors were delivered by subcutaneous injection directly over the surface of the superior gluteus muscle once daily for 7 d and then end plates and axons were visualized by combined silver and cholinesterase staining. CNTF (500 ng daily) induced sprouting both from end plates and from the subset of nodes of Ranvier that are closest to the end plate. The effect of CNTF was potentiated twofold by coadministration of bFGF at doses of 2-20 ng daily, whereas treatment with bFGF alone failed to induce sprouting from either end plates or nodes of Ranvier. The sprouting stimulus delivered by the factors showed limited penetrance into the muscle and restricted lateral spread from the injection site.


Dynamics of terminal arbor formation and target approach of retinotectal axons in living zebrafish embryos: a time-lapse study of single axons. In a variety of species, developing retinal axons branch initially more widely in their visual target centers and only gradually restrict their terminal arbors to smaller and defined territories. Retinotectal axons in fish, however, appeared to grow in a directed manner and to arborize only at their retinotopic target sites. To visualize the dynamics of retinal axon growth and arbor formation in fish, time-lapse recordings were made of individual retinal ganglion cell axons in the tectum in live zebrafish embryos. Axons were labeled with the fluorescent carbocyanine dyes Dil or DiO inserted as crystals into defined regions of the retina, viewed with 40x and 100x objectives with an SIT camera, and recorded, with exposure times of 200 msec at 30 or 60 sec intervals, over time periods of up to 13 hr. (1) Growth cones advanced rapidly, but the advance was punctuated by periods of rest. During the rest periods, the growth cones broadened and developed filopodia, but during extension they were more streamlined. (2) Growth cones traveled unerringly into the direction of their retinotopic targets without branching en route. At their target and only there, the axons began to form terminal arborizations, a process that involved the emission and retraction of numerous short side branches. The area that was permanently occupied or touched by transient branches of the terminal arbor--"the exploration field"--was small and almost circular and covered not more than 5.3% of the entire tectal surface area, but represented up to six times the size of the arbor at any one time. These findings are consistent with the idea that retinal axons are guided to their retinotopic target sites by sets of positional markers, with a graded distribution over the axes of the tectum.


Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus. Innervation of specific peptidergic and cholinergic compartments of the interpeduncular nucleus (IPN) was investigated using embryonic cell suspension transplants immunoreactive for substance P (SP) and ChAT. In both neonatal and adult host rats, the IPN was first denervated of its normal SP and cholinergic input from the medial habenula by bilateral lesions of the fasciculi retroflexi (FR). In adult hosts, transplants of embryonic habenular cells placed near the denervated IPN mediated a return of the normal pattern of SP staining restricted to habenula-target subnuclei, plus an increase in staining intensity of SP cells intrinsic to the IPN. There was no recovery of ChAT staining. A similar pattern of SP staining resulted following habenular transplants into neonatal hosts, but in addition there was a partial recovery of normal ChAT staining in cholinergic subnuclei and anomalous ChAT staining in normally peptidergic subnuclei. Control transplants of embryonic thalamus cells placed into adult hosts produced a surprising pattern of ChAT staining in the IPN identical to that seen with habenula transplants placed into neonatal hosts; the adult IPN was thus able to support reinnervation mediated by an aberrant cholinergic source while being refractory to its normal habenular cholinergic afferents. This pattern of results implies regulation by the IPN of habenular SP and cholinergic innervation, and some interaction between the maturing normal cholinergic afferents and their targets that is missing when these afferent sources are abnormal.


Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus. The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the "flower pot" test, and assayed (1) normal adult rats, (2) FR-lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS)


Finger systolic blood pressure measurements after finger cooling. Using the laser-Doppler method for assessing vibration-induced white finger. Finger systolic blood pressure (FSBP) measurements after finger and body cooling using a strain-gauge plethysmograph is a useful objective test for diagnosing Raynaud's phenomenon (RP). Body cooling, however, is uncomfortable to subjects. In this study, the measurements of FSBP after finger cooling without body cooling, using Digitmatic DM2000 (Medimatic) combined with laser-Doppler flowmetry (ALF2100 Advance), were performed in 99 vibration-exposed men (40 men without RP, 39 men with mild RP, and 20 men with severe RP) and 13 healthy controls. This method is relatively useful for assessing the severity of vibration-induced white finger (VWF).


Activation of blood platelets in workers exposed to organic solvents. Organic solvents probably exert their clinical effects through distortion of cellular membrane structure and function. Blood platelets represent an easily available membrane system. This study describes an evaluation of mean platelet volume (MPV) and total platelet count (TPC) in a group of workers exposed to a mixture of organic solvents in paint factories. We have found a correlation between decreased MPV and present exposure. The reduction was reversed within an exposure-free interval of 3 weeks. The intracellular adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio was significantly increased in exposed workers, compatible with dense granule secretion. A quantitative study of the phosphoinositide cycle in the platelets revealed an increased concentration of the phosphatidic acid, indicating an increased turnover. These findings are consistent with a solvent-induced activation of circulating platelets.


Workplace smoking restrictions, occupational status, and reduced cigarette consumption. Reductions in workday cigarette consumption among indoor workers subject to different levels of smoking restriction were examined using representative population data for both blue-collar and white-collar workers. Regardless of whether workplace smoking bans were total or applied only to the usual work station, reported workday cigarette consumption was reduced by approximately five cigarettes per day compared with leisure-day consumption. This was in contrast to there being no difference between workday and leisure-day consumption among those who had no ban on smoking at their usual work station. This pattern of findings applied to all occupational-status groups, after controlling for sex and number of cigarettes smoked on a leisure day. These results are discussed with reference to potential public-health benefits and to implications for reduced retail sales of cigarettes.


Persistent brominated and chlorinated dioxin blood levels in a chemist. 35 years after dioxin exposure. This is the first report on occupational health hazards to dioxin chemists associated with laboratory exposure to 2,3,7,8-tetrabromodibenzodioxin (TBrDD), and further characterizes the human response to 2,3,7,8 tetrachlorodibenzodioxin (TCDD). In this case study the chemist was exposed on two separate occasions. In March 1956, after synthesizing 10 g of TBrDD, the chemist suffered from mild and transient chloracne of the neck and wrists; in September 1956, after synthesizing 16 g of TCDD, he suffered severe chloracne of the entire body, headaches, backache, and leg pain on exertion. His measured 2,3,7,8-TBrDD in 1991 was 625 parts per trillion (ppt) in whole blood lipid, 35 years after initial exposure and 18 ppt TCDD, an elevated level in comparison with the mean 2,3,7,8-TCDD level of 5 ppt in the US population. This is the first reported detection of a brominated dioxin in human tissue. The total halogenated dioxin body burden in September 1956 is estimated to have been between 13,005 ppt and 146,726 ppt. This amount can be considered to be, at least in this person, a strong chloracnegenic dose, and a dose causing human nervous system and muscular or circulatory system responses. This uptake demonstrates an occupational hazard to chemists and chemical workers, and the usefulness of human tissue dioxin measurements to document absorption.


Mental health, constraints, and organization of work as interactive variables. A study of word processing secretaries. The effect of a work constraint is specific to the type of work organization. This article deals with the effects of different types of work organization on the mental health of secretaries. The advantage of choosing secretarial work as a research subject lies in the fact that we can identify three distinct types of work organization: (1) a secretary working directly for someone (the "paired" secretary-boss), (2) the "pool," geared toward keyboard input with no specific pairing of secretaries and authors, and (3) the departmental "team," a hybrid of the two preceding types, characterized by the presence of several secretaries, each one assigned to several authors. A study was conducted on the health problems reported by secretaries in the Québec civil service. Data available from a Santé Québec study, carried out at the same time, allowed us to constitute a general population reference group of secretaries and other working women. The findings indicate that secretaries in the general population are no more at risk than are other similar working women, but that secretaries in the provincial civil service are at risk. Regression analysis shows that the same traditional constraints do not affect secretaries in the same way regardless of whether they are members of pair, pool, or team organizations. This suggests that the context of work organization is an interactive or a "specifying variable" of the effect of work constraints on the secretaries' mental health.


The impact of legislation on self-reported safety belt use in a working population. To assess the impact of safety belt laws, we compared self-reported use of safety belts among employed residents of states with primary, secondary, and no laws in a group of 17,830 volunteer health profile participants. Failure to wear safety belts at least 80% of the time was reported by 22% of subjects covered by primary laws, 23% of those covered by secondary laws, and 39% of those not covered by any law.


Latent period for malignant mesothelioma of occupational origin. To estimate the minimal latent period for malignant mesothelioma of occupational origin, we reviewed 21 articles that documented latent periods for malignant mesothelioma, totaling 1690 cases. Of these, 1105 (65%) cases fulfilled the strict histologic and exposure criteria and were included in this analysis. Of these mesotheliomas, 99% had a latent period more than 15 years; 96% had a latent period of at least 20 years; and the observed probability of an occupational exposure within a decade of the first exposure was zero. The estimated median latent period was at least 32 years after the initial exposure. These epidemiologic conclusions are important in determining the source of a specific case of the disease, understanding the natural history of the disease, determining liability, and in aiding in the diagnosis of malignant mesotheliomas of occupational origin.


Mental and psychosomatic work injuries in Sweden. In Sweden, persons who incur illness or injury at work or on the way to or from work may claim indemnity under a work injuries insurance scheme. A new law in 1977 included mental and psychosomatic illnesses. Looking into the records of reported work injuries in Gothenburg 10 years later, we found 67 cases diagnosed as mental or psychosomatic illnesses. One third of these were accepted as work injuries. The cited harmful influence mostly referred to mental and/or physical strain from work itself. Traumatic incidents, maltreatment by the employer, and persecution also were accepted as harmful influences. Comparison with an earlier study revealed that although the rate of approbation for mental and psychosomatic work-related illnesses (about 30%) is much lower than for all work-related illnesses (about 90%), there has been a considerable increase over the years.


Use of medical insurance claims for surveillance of occupational disease. An analysis of cumulative trauma in the auto industry. Medical insurance claims, linked with work histories for a large automotive manufacturer over a 3-year period, identified large numbers of cases of potentially work-related diseases, including 30,600 episodes of probable cumulative trauma disorders (CTD). CTD incidence rates were calculated within five plants, and high-risk areas identified, however, unknown differences in medical insurance coverage by exposure group limited interpretation. Case-control analyses, with controls also identified by insurance claims, addressed coverage and produced age-adjusted and sex-adjusted estimates of risks. All five plants had departments with statistically significant, elevated risks for one or more of the diagnoses carpal tunnel syndrome, CTD of other upper extremities, rotator cuff syndrome, CTD of the neck and of the lower back. Medical insurance claim data linked with work history provide the basis for practical and comprehensive surveillance for CTD and potentially a variety of other occupational diseases.


Nurses' role in preventing birth defects in offspring of women with phenylketonuria. Most women who began nutrition support as neonates for a diagnosis of phenylketonuria, an inherited defect in phenylalanine metabolism, are of normal intelligence, no longer require a restricted diet, and wish to have children of their own. Phenylketonuria that is untreated when a woman conceives and during gestation results in poor reproductive outcomes. Treatment with and careful monitoring of a phenylalanine-restricted diet can improve reproductive outcome. Nurses have the primary responsibility in locating women of childbearing age with phenylketonuria; developing strategies to improve palatability of the diet, thereby enhancing compliance; providing ongoing monitoring and support of the mother-child dyad; and counseling couples at risk.


Reanalysis of lambda max variations in the Stiles-Burch 10 degrees color-matching functions. Individual differences in the color matches made by normal observers can be attributed in part to small interobserver variations in the spectral peaks (lambda max) of the cone sensitivities. I compared two different analyses of these lambda max variations that were both based on the Stiles-Burch 10 degrees color-matching functions [Opt. Acta 6, 1 (1959)]: one that suggested that the lambda max values for individual cone classes fall into discrete subgroups [J. Neitz and G. H. Jacobs, in Colour Vision Deficiencies IX, B. Drum and G. Verriest, eds. (Kluwer Academic, Dordrecht, The Netherlands, 1989)] and one that failed to find discrete clustering [J. Opt. Soc. Am. A 5, 1722 (1988)]. I conclude that there is not strong evidence for discrete lambda max variations in the Stiles-Burch matches.


Maternity blues and postpartum depression. To investigate the relationship between maternity blues and postpartum depression in mothers discharged early from the hospital and those discharged after the customary length of hospital stay. A descriptive correlation design. 550-bed community and teaching hospital in the midwestern United States. 49 privately paying, primiparous, American-born women, 18 years of age or older, with uncomplicated pregnancies and vaginal deliveries of healthy neonates weighing 2,600-4,000 g. Stein Maternity Blues Scale and Beck Depression Inventory were used to collect data. No significant differences found between the two groups of mothers; significant relationships found between maternity blues at 1 week after delivery and postpartum depression at 6 and 12 weeks after delivery. Early discharge appears to pose no threat to psychologic well-being. Primiparas experiencing more severe maternity blues are at increased risk for postpartum depression.


Effect of carrageenan-induced inflammation on the induction of hepatic microsomal enzymes by phenobarbital and benzo[a]pyrene in male rats. The inhibitory effect of carrageenan-induced inflammation was examined by utilizing rats treated with inducers of this drug metabolizing system. Animals were given sodium phenobarbital (PB, 80 mg/kg, i.p., 24 h prior to death), or benzo[a]pyrene (BP, 40 mg/kg, i.p., 24 h prior to death) as inducers. Some animals were also given carrageenan 24 h prior to death. Non-induced male rats exhibited significant decreases in hepatic 9000 x g supernatant (S-9) cytochrome P-450 and aminopyrine (AM) N-demethylase, benzphetamine (BenzP) N-demethylase and meperidine (MP) N-demethylase activity following carrageenan treatment. Carrageenan also depressed the induction of hepatic S-9 cytochrome P-450 content caused by PB treatment, and suppressed the induction of AM, BenzP, MP, arylhydrocarbon and 7-ethoxycoumarine metabolism by PB treatment. Cytochrome P-450 levels and related biotransformation activity which are elevated by BP treatment were not decreased by the injection of BP and carrageenan simultaneously to male rats. Non-induced, PB-treated and BP-treated female rats did not show inhibited carrageenan-induced reduction in hemoprotein content or inhibition of AM-N-demethylase, BenzP N-demethylase and aniline hydroxylase activities. These results demonstrate the selective nature of the inhibitory effects of carrageenan-induced inflammation upon drug metabolism in the rats.


Biochemical studies on oral toxicity of ricin. IV. A fate of orally administered ricin in rats. After oral administration of ricin in rats, its distribution in the gastrointestinal tract, body fluids and principal organs was determined by an enzyme immunoassay, and the immunoreactive ricin detected was identified by gel filtration followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, protein blotting and the immunobinding method. When ricin D (10 mg/kg rat) was given orally to a rat, which dose is equivalent to 1/3 LD50, about 75% of the ricin was found in the stomach and small intestine within 2 h, and most of it was transferred to the large intestine after 24 h. It was also demonstrated by an in vitro toxicity test of immunoreactive ricin in the blood and lymph obtained from the intoxicated rats that a part of the ricin was absorbed from the small intestine into the tissues and organs via the circulatory systems (lymphatic and blood vessels) as the active ricin. The participation of the blood vessels was greater in the absorption of ricin from the gastrointestinal tract than that of the lymphatic system. Ricin, after absorption, was detected in liver and spleen and ricin found in the liver was predominantly in the form of intact ricin, although an undetectable amount of ricin in other organs cannot be eliminated. These results infer that a small fraction of orally-given ricin was transferred to the circulating system and was responsible for rat's death as in the case of i.p. administration.


Pharmacokinetic analysis of amitriptyline and its demethylated metabolite in serum and brain of rats after acute and chronic oral administration of amitriptyline. The compartmental model analysis by use of simultaneous curve fitting was carried out to ascertain the pharmacokinetic relationship between amitriptyline (AMT) and nortriptyline (NRT) in the serum and brain after acute or chronic oral administration of AMT. The estimated F value, a fraction of dose reached at systemic circulation, and the MD value, a fraction metabolized to NRT, were 0.044 and 0.020, respectively, after acute administration, indicating first-pass metabolism of AMT. The estimated parameters kin and kout, the transfer rate constants to and from the brain, showed no marked difference between AMT and NRT. These findings indicate equivalent ability of AMT and NRT to penetrate into the brain. The area under the concentration curve (AUC) values of AMT and NRT in the serum increased 1.4 and 8.2 times, respectively, with the increase of NRT being greater after chronic administration. The MD value was increased from 0.020 to 0.096, whereas the estimated F value showed no marked change. These results indicate the enhanced first-pass metabolism. The estimated transfer rate constants kin and kout of AMT were close to those of NRT. In addition, the transfer rate constants after chronic administration were similar to those after acute administration, indicating no marked change in penetration into the brain by multiple dosing.


Improving access to and use of prenatal care. Inadequate prenatal care is one of the most perplexing problems in obstetrics. Many women do not seek prenatal care early, and some obtain no prenatal care. The history of prenatal care, the impact of inadequate prenatal care, and the many factors involved in access to and use of prenatal care are discussed. Nursing implications aimed at exploring ways of reducing these factors are examined.


Distribution of quinidine in rats with carbon tetrachloride-intoxicated hepatic disease. The disposition of quinidine was investigated in rats with experimental hepatic disease caused by an intraperitoneal injection of CCl4. The plasma disappearance of quinidine after a 12.5 mg/kg i.v. bolus injection was analyzed by a two-compartment open model in both control and CCl4-intoxicated rats. In the CCl4-intoxicated rats, plasma total body clearance (CLtot), elimination rate constant of the central compartment (kel) and the volume of distribution (Vdss) of quinidine were decreased by 73, 51 and 36%, respectively, compared to those in the control rats. At a steady state of quinidine plasma concentration of 1 micrograms/ml, tissue-to-plasma partition coefficient (Kp,vivo) of the drug in the lung, spleen, heart, kidney and liver in the CCl4-intoxicated rats were decreased ranging from 32 to 42% compared to those in the control rats. The plasma free fraction of quinidine in the intoxicated rats was decreased by 34% of that in the control rats. Neither tissue binding of quinidien in vitro, nor plasma pH was altered in the intoxicated rats. Thus, the decrease in Vdss and Kp,vivo for quinidine in the intoxicated rats seems likely to be due to an increase in plasma protein binding of the drug. Metabolic activity in the liver, the hepatic extraction ratio for quinidine, and the hepatic blood flow in the CCl4-intoxicated rats were decreased by 84, 57 and 47%, respectively, compared to those in the control rats. The decrease in CLtot and kel in the intoxicated rats is considered to be attributed to both the reduction of liver functions and the increase in the plasma protein binding of the drug.


Biofeedback-assisted relaxation to reduce stress in labor. To test the feasibility and effectiveness of incorporating biofeedback-assisted relaxation techniques into routine instruction in Lamaze classes. A quasi-experimental design (static groups comparison) was used. Lamaze classes. A convenience sample of 33 subjects recruited from 12 Lamaze classes. Duration of first-stage labor, amount of sedation and analgesia during first-stage labor, number of complications, and 1- and 5-minute Apgar scores of the neonates. The experimental subjects reported greater stress during labor than did the control subjects. Although the supplementary instruction in reducing stress seemed to promote relaxation during the prenatal classes, it did not reduce distress during labor and delivery because no mothers attempted to use the technique at that time.


Intrapartum care of a woman with aortic aneurysms. Advances in technology and complex care have enabled women with various health problems to become and remain pregnant. Consequently, health-care practitioners are seeing an increasing number of pregnant women who have aortic aneurysms. This case study describes the culturally sensitive intrapartum care of a Middle Eastern woman with ascending and descending aortic aneurysms.


Suppression by high glucose concentration of insulin receptor up-regulation in diaphragm and flexor digitorum brevis muscles from diabetic KK-CAy and streptozotocin-diabetic mice. The specific binding of insulin to diaphragm and flexor digitorum brevis (FDB) muscles isolated from diabetic KK-CAy and streptozotocin (STZ)-diabetic ddY mice was investigated under high glucose concentration in vitro. For high-affinity insulin receptor under 2.8 mM glucose, amounts of the receptor and values of dissociation constant (Kd) were greater in both diabetic muscles than in the corresponding normal control muscles, respectively. High glucose concentration up to 16.7 mM reduced both the up-regulation of the receptor and the decrease in the affinity by the diabetic state. These studies strongly suggest that high glucose level in the diabetic state in vivo may suppress the up-regulation of high-affinity insulin receptor in both models of diabetic mice.


Accumulation of propranolol in cultured rat fibroblasts. In order to clarify the involvement of phosphatidylserine (PhS) in the cellular accumulation of propranolol, we have characterized the binding of 3H-propranolol to cultured rat fibroblasts and to liposomes containing PhS. The properties of propranolol binding to the cells and liposomes were analyzed by means of a Scatchard plot. The cells contained at least two classes of propranolol binding sites, one site of high affinity/low capacity and the second site of lower affinity/higher capacity, while the liposomes contained only one class of binding site. The values of the association constant (K) and number of binding sites (n), given on a PhS basis for the propranolol binding site in the liposomes, were both very close to those of corresponding binding parameters for the high affinity/low capacity binding site in the cells. Cell death, caused by various toxic reagents, resulted in a marked decrease in propranolol accumulation in the cells. Kinetic analysis of the drug binding to dead cells showed one binding site with binding parameters comparable to those of the low affinity/high capacity binding site in the intact cells. Polar cations, methylamine and NH4Cl, completely inhibited propranolol binding to the liposomes. On the other hand, these cations partially inhibited propranolol accumulation in intact cells and failed to inhibit the drug binding to dead cells. These results suggest that PhS in cytomembranes represents the high affinity/low capacity propranolol binding site in cultured rat fibroblasts.


Integration of the big five and circumplex approaches to trait structure. To integrate the 5-dimensional simple-structure and circumplex models of personality, the Abridged Big Five Dimensional Circumplex (AB5C) taxonomy of personality traits was developed, consisting of the 10 circumplexes that can be formed by pitting each of the Big Five factors against one another. The model maps facets of the Big Five dimensions as blends of 2 factors. An application to data consisting of 636 self-ratings and peer ratings on 540 personality trait adjectives yielded 34 well-defined facets out of a possible 45. The AB5C solution is compared with simple-structure and lower dimensional circumplex solutions, and its integrative and corrective potential are discussed, as well as its limitations.


Affect intensity and cardiac arousal.

Affect intensity and cardiac arousal. Relationships between affect intensity and basal, evoked, and perceived cardiac arousal were investigated in 3 experiments. Affect intensity was assessed using Larsen and Diener's (1987) Affect Intensity Measure (AIM). Cardiac arousal was evoked with exercise in the 1st study and with mental arithmetic in the 2nd and 3rd. Perceived cardiac arousal was measured under optimal conditions using a standard heartbeat discrimination procedure. Women as a group scored higher on the AIM. Affect intensity was unrelated to basal or evoked cardiac arousal and was negatively related to perceived cardiac arousal in all 3 studies. Data suggest that affect intensity, although unrelated to actual physiological arousal, is negatively related to the accuracy with which individuals perceive their own arousal. Results are discussed within the context of an expanded arousal-regulation model (Blascovich, 1990).


Self-fulfilling effects of stigmatizing information on children's social interactions. The stigmatizing effects of negative expectancies were examined in observations of interactions between children with and without a behavior problem. Ss were 68 pairs of unacquainted boys in Grades 3-6. In each dyad, a normal boy was either told that his partner had a behavior problem or given no expectancy; this expectancy manipulation was crossed with the partner's actual diagnostic status with respect to hyperactivity. The perceivers' expectancy that their partner had a behavior problem as well as the actual diagnostic status of the target adversely affected the boys' interactions. Behavioral data suggest how the expectancies were communicated to the target. The processes underlying interpersonal expectancy effects and the ways in which a childhood stigma can act as a self-fulfilling prophecy are discussed.


Possible self-complexity and affective reactions to goal-relevant evaluation. The complexity of people's self-concept appears to be inversely related to the intensity of their reactions to evaluative feedback about present goals and abilities (Linville, 1985, 1987). The idea that the complexity of individuals' possible self-concept similarly mediates reactions to feedback regarding future goals was investigated. Two preliminary studies suggested that complexity of the actual self only explains 20% to 30% of the variance in possible self-complexity. Three studies were conducted. Support was found for the idea that possible self-complexity mediates affective reactions to evaluative feedback about future goals and actual self-complexity mediates affective reactions to evaluative feedback about present goals. The findings underscore the independent roles of the organization of actual and possible self-concepts in affective processes.


Emotional disclosure about traumas and its relation to health: effects of previous disclosure and trauma severity. This study sought to replicate previous findings that disclosing traumas improves physical health and to compare the effects of revealing previously disclosed versus undisclosed traumas. According to inhibition theory, reporting about undisclosed traumas should produce greater health benefits. Sixty healthy undergraduates wrote about undisclosed traumas, previously disclosed traumas, or trivial events. Contrary to expectations, there were no significant between-groups differences on longer term health utilization and physical symptom measures. However, Ss who disclosed more severe traumas reported fewer physical symptoms in the months following the study, compared with low-severity trauma Ss, and tended to report fewer symptoms than control Ss. Results suggest that health benefits occur when severe traumas are disclosed, regardless of whether previous disclosure has occurred.


Evidence for genetic influences on personality from self-reports and informant ratings. Self-report data on Extraversion (E) and Neuroticism (N), together with ratings by the co-twin, were obtained from a sample of 826 adult female twin pairs ascertained through a population-based twin register. Data were analyzed using a model that allowed for the contributions to personality ratings of the rater's personality (rater bias) as well as of the personality of the person being rated. For E, but not for N, significant rater bias was found, with extraverted respondents tending to underestimate, and introverted respondents tending to overestimate, the Extraversion of their co-twins. Good agreement between self-reports and ratings by the respondent's co-twin was found for both E and N. Substantial genetic influences were found for both personality traits, confirming findings from genetic studies of personality that have relief only on self-reports of respondents.


[A multichannel telemetry system for autonomic neural signals, blood flow velocity, blood pressure, and ECG measurements]. A radio multichannel telemetry system has been developed for use with chronically instrumented, unrestrained, small animals. The system can simultaneously record autonomic neural signals, blood flow velocity, blood pressure, and ECG. The system is time-multiplexed and pulse width modulation (PWM)/FM device, which employs two sampling frequencies. The system is designed with 10 standard low power integrated circuits, a 3 terminal voltage regulator, and a transistor. The size is 53 x 42 x 20 mm, and the weight, including two batteries is 40 grams. The system is powered by two lithium cells, which provide 60 hours of continuous operation.


Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. Providing adequate pain control with minimal side effects in inpatient and ambulatory settings is a continuous challenge to the PACU nurse. Ketorolac tromethamine (Toradol, Syntex, Palo Alto, CA) is a new parenteral nonsteroidal anti-inflammatory drug (NSAID) approved for use in the United States. Ketorolac is useful in the management of short term, moderate to severe postoperative pain. It is used by itself or as an adjunct to traditional opioid analgesics. Ketorolac, like other NSAIDs, has analgesic, anti-inflammatory, and antipyretic properties. Unlike morphine or meperidine, ketorolac does not bind to opioid receptors and is not a centrally acting agent. Administered intramuscularly, peak plasma levels are reached in 45 to 50 minutes. It is administered as a 30- or 60-mg intramuscular (IM) loading dose followed by 15- or 30-mg doses IM every 6 hours, with a maximum first-day dose of 150 mg and 120 mg on subsequent days up to a recommended maximum of 5 days. The lower dose range is recommended for elderly patients, patients weighing less than 50 kg, and patients with impaired kidney function. Initial studies show that use of ketorolac decreases the overall amount of opioid analgesia needed for postoperative pain control. To date, reported occurrence of side effects is low. A case study presents a healthy ambulatory surgical patient admitted for inguinal hernia repair using epidural anesthesia. Use of ketorolac has shown initial favorable results. More research is needed to further define its role and side effects in postoperative pain management.


The effects of television viewing on preoperative anxiety. Previous studies have looked at the relationship between preoperative anxiety and postoperative course. However, few studies have looked at methods to decrease preoperative anxiety. To investigate preoperative anxiety and possible anxiety reduction strategies, the investigators devised a clinical study to examine the effects of television viewing on preoperative anxiety. The study compared patients who were not able to watch television in the preoperative setting with those who were. The investigators hypothesized that television viewing in the preoperative setting would decrease preoperative anxiety. A purposive sampling method was chosen so that the study population could be selected using certain criteria. The sample consisted of adult patients 18 to 77 years old who were admitted to the preoperative area at least 2 hours before surgery. A total of 76 subjects participated in the study. However, due to incomplete data on seven of the questionnaires, 7 of the subjects were rejected. Of the remaining 69 subjects, 39 had no television access and the remaining 30 did. Statistical comparisons of the two groups suggest that there was a significant difference in the anxiety levels of the two groups. As hoped, the hypothesis was proven correct: Those subjects who watched television in the preoperative area had significantly lower levels of anxiety than those who did not.


Is it a contact hour, a continuing education recognition point, or a continuing education unit? Based on the content of this article, the reader should be able to: (1) differentiate between a contact hour, a continuing education recognition point, and a continuing education unit; (2) identify states that require mandatory continuing education for relicensure; and (3) define certification.


When paradigms shift.

When paradigms shift. Paradigms are models that define boundaries and expected behavior. The health care paradigm is changing, and this shift from the old to the new model presents a real challenge to each manager who is trying to maintain a productive, cohesive staff.


Responding to change in the decade of dilemma. Virtually every politician seeking public office has proposed a national health care plan. Attempts to reduce the cost of health care have been less than successful. Indeed, cooperative action in dealing with health care problems is unlikely during this election year and probably for some time to come. In the following article the author shares some observations and predictions about the political, economic, social, and educational factors that will influence nursing practice in the 1990s, the decade of dilemma.


Educating patients about missed medication doses. 1. Missed-dose management, or the handling of a forgotten or omitted dose, is a necessary self-care skill for persistently and severely mentally ill patients. 2. A missed dose should generally be taken as soon as it is remembered, and doses should not be doubled. 3. Individual drug-specific instructions about missed-dose management are available for antipsychotics, antidyskinetics, and lithium. 4. Teaching patients about missed-dose management as well as the use of reminders to minimize missed doses are important nursing activities.


A new nursing medium: computer networks for group intervention. The PLWAs and the caregivers of persons with AD were similar in their adaptation to this new technology as a communication medium with nurses. Both groups availed themselves of the resources, both technological and personal, on the computer network. Although different in demographics, they also were similar in their ability to form and work in a traditional group structure. Nurses have historically intervened with groups, and this article demonstrates that nurses can intervene on a computer network with groups. Yalom's therapeutic factors exist in both non-face-to-face groups and traditional groups. The benefits of this technology to nurses are numerous: they can access clients in an efficient yet supportive manner; they can respond to multiple levels of need in multiple clients; and they can attend to emotional as well as more concrete needs of clients. The benefits to clients are also numerous: they can use the system at a time, frequency, and duration of their choice; they have the opportunity to be supported in self-care efforts versus being in a more dependent role; and they can engage in a normalization of their experiences. Computer networks can enhance nursing's ability to intervene with clients experiencing clinical problems.


Therapeutic listening: developing the concept. 1. Therapeutic listening is an art that all nurses, especially psychiatric nurses, must possess to be effective. Listening has been listed as the most effective therapeutic technique available. 2. Therapeutic listening is an interpersonal confirmation process, involving all the senses, in which the therapist attends with empathy to the client's verbal and nonverbal messages to facilitate the understanding, synthesis, and interpretation of the client's situation. 3. The therapeutic listening process includes maintaining eye contact; an attending posture; staying within conversational distance; responding with facial expressions, touch, gestures, and encouraging words; asking relevant questions; and interpreting and summarizing key points using specific words spoken by the client.


Pulling together: building a community debriefing team. 1. Research shows that many emergency workers are affected physically and emotionally by critical incident stress. 2. Debriefings conducted by trained team members are an effective method to mitigate the impact of critical incident stress. A debriefing is a structured, time-limited group intervention. 3. Cooperation among community agencies is essential for the development and effective functioning of a critical incident stress debriefing team. 4. Several teams in Illinois have organized to form a Critical Incident Stress Debriefing Network. The Illinois network is part of an international organization composed of critical incident stress debriefing providers.


Teaching hospitalized patients with serious, persistent mental illness. 1. Although patient teaching is an important nursing function, minimal research was found related to education of patients with schizophrenia. Teaching psychiatric patients about illness, treatment, and rehabilitation has not received the same attention in psychiatric nursing as it has in other nursing specialties. 2. Eighty percent of the patients who participated in patient education classes would recommend the program to others. Treatment teams reported that some patients asked more questions about their treatment and became more active in ward groups following the classes. 3. The use of nurses as patient educators facilitates professional nursing practice and effectively ensures that patients' general physical health and psychiatric education needs are systematically addressed.


Confidence builders: a self-esteem group at an inpatient psychiatric hospital. 1. Many people with mental illness experience low self-esteem. They tend to minimize their own positive attributes, strengths, and abilities, making it difficult to accept positive feedback. 2. As an alternative to the one-to-one relationship, the Self-Esteem Group provides a situation in which self-esteem can be increased through constructive social interactions, trust, and support from group members. 3. Structured exercises, which encourage sharing and development of positive aspects of self, were completed by group members during each session. These exercises made it easier for group members to focus ideas, feelings, and experiences related to the topic for discussion.


Effects of hyperthermia induced by microwave irradiation on brain development in mice. Pregnant mice were exposed to 2.45 GHz of microwave radiation for 15 or 20 min on day 13 of gestation. The highest maternal core temperature during the exposure did not exceed 42.5 degrees C. Pregnant females also were immersed in hot water at 42 degrees C for 15 min to compare thermal effects on brain development. Animals were killed 9 hours after treatment, and the pyknotic cells in the ventricular zone of telencephalon were counted. The respective incidences of these cells in the groups exposed to microwaves for 15 and 20 min were 1.83% and 3.06%. Microwave radiation for 20 min had an effect that was comparable to that of immersion in 42 degrees C hot water for 15 min. In addition, some animals were examined on day 18 of gestation, and some of their offspring were examined at 6 weeks of age in an examination of long-term effects. Brain weight for the group exposed to microwaves for 20 min was significantly lower than for the control group, and the numerical density of the neurons in the cerebrum was higher. We concluded that microwave radiation at the dose tested mainly has a thermal effect.


Rapid decrease in brain enkephalin content after low-dose whole-body X-irradiation of the rat. Methionine-enkephalin (ME) contents in the hypothalamus and other rat brain structures were measured immediately after 10 or 20 cGy whole-body X-irradiation. The ME contents of homogenates of the striatum, hypothalamus, midbrain + thalamus, hindbrain and pituitary were assayed radioimmunologically with 125I. The contents of all the structures, except the pituitary, decreased significantly after 20 cGy irradiation. The reduction in the hypothalamus was transient, ME content gradually recovering with time. These results suggest that the central nervous system of mammals is one of the most radiosensitive organs as judged by changes in stress-induced mediators such as ME.


3'-Spiro nucleosides, a new class of specific human immunodeficiency virus type 1 inhibitors: synthesis and antiviral activity of [2'-5'-bis-O-(tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranose]-3'-spiro-5"-[4"-amino-1",2"-oxathiole 2",2"-dioxide] (TSAO) pyrimidine nucleosides. A series of 3'-spiro nucleosides have been synthesized and evaluated as anti-HIV-1 agents. Reaction of O-mesylcyanohydrins of furanos-3'-ulosyl nucleosides with base afforded [1-[2',5'-bis-O- (tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranosyl]]-3'-spiro-5"- [4"-amino-1",2"-oxathiole 2",2"-dioxide] derivatives of thymine, uracil and 4-N-acetylcytosine 11 and 12. Desilylation of 11 and 12 gave the full deprotected 3'-spiro xylo- and ribofuranosyl nucleosides 13 and 14 or the partially 5'-O-deprotected-3'-spiro beta-D-xylo- and -ribo-nucleosides 15 and 16, or 2'-O-deprotected-3'-spiro beta-D-ribo-nucleoside 17. 2'-Deoxygenation of 17 afforded 2'-deoxy-3'-spiro beta-D-erythro-pentofuranosyl derivative 18. These 3'-spiro derivatives were evaluated for their anti-HIV-1 activity. All 3'-spiro nucleosides having a xylo configuration did not show any anti-HIV-1 activity. 3'-Spiro ribo-nucleosides with none or only one silyl group at C-2' or C-5' or the 2'-deoxy derivative were also inactive at subtoxic concentrations. However, 3'-spiro ribo-nucleosides having two silyl groups at C-2' and C-5' were potent and selective inhibitors of HIV-1. None of the nucleoside analogues that showed anti-HIV-1 activity proved inhibitory to the replication of HIV-2 or SIV.


Potential prodrug derivatives of 2',3'-didehydro-2',3'-dideoxynucleosides. Preparations and antiviral activities. The preparations and antiviral activities of a series (4-17) of potential prodrug forms of the antivirals 2',3'-didehydro-2',3'-dideoxyadenosine (D4A) and 2',3'-didehydro-2',3'-dideoxycytosine (D4C) are reported. The 5'-phenyl- and 5'-methylphosphonates (4, 6, 8, and 10) and their phosphonothionate congeners (5, 7, 9, and 11), with the exception of 10, were inactive in vitro against HIV-1 and HIV-2. However, the 5'-phenyl, 5'-methyl, and 5'-(3'-thymidyl) phosphate diesters (12-17) demonstrated inhibition of the cytopathic effect of HIV-1 and HIV-2 (EC50 approximately 1-60 microM) and cytotoxicities (CC50 approximately 35-200 microM) at concentration levels comparable to those of their parent compounds, D4A and D4C. This strongly suggests that the diesters are hydrolyzed to the nucleosides D4A and D4C and/or their 5'-monophosphates. The facile hydrolysis of 12 and 13 to these products was demonstrated in a medium containing 10% fetal calf serum. The molecules can serve as ready prodrug sources of the free nucleosides and their 5'-monophosphates. Evidently, the phosphonates and phosphonothionates are not similarly cleaved, nor are they phosphorylated to form antivirally active or cytotoxic products. The importance of intracellular formation of these products in the activation of 12-17 is less clear. Potential prodrugs 4-17 are all stable in aqueous solution for hours with the exception of 14. Conjugates 4-17 showed no activity against a series of DNA and RNA viruses.


HIV-1 neutralization and tumor cell proliferation inhibition in vitro by simplified analogues of pyrido[4,3,2-mn]thiazolo[5,4-b]acridine marine alkaloids. The antiviral/antitumor marine alkaloid dercitin was used as a lead compound to design analogues with anti-HIV and tumor inhibitory activities. Deletion of structural features contributing to cytotoxicity led to analogues with lowered T-lymphocyte toxicity profiles. One compound, 5, induced complete protection against HIV-1 infectivity in vitro at 12.5 micrograms/mL (38 microM) without T-cell toxicity up to 400 micrograms/mL. Compound 4 and 5 also inhibited the binding of HIV-1 to H-9 lymphocytes. These compounds may exert antiviral activity by a unique dual extracellular and intracellular mode of action--both preventing viral attachment to lymphocytes as well as intercalating with viral nucleic acid. Analogues with higher cytotoxicity such as 2 which retain the thiazole ring of the natural product proved effective in completely inhibiting the cell proliferation of breast, colon, and lung tumor cell lines at 1.5 microM concentration compared to a 70 microM dose level of 5-fluorouracil. A means of molecular separation of antiviral activity from cytotoxicity was thus achieved, and putative pharmacophores for antiviral and antitumor actions of the prototype molecule dercitin have been deduced. The 2-thio-9-acridinone derivatives 4 and 5 represent a new structural type exhibiting activity against HIV in vitro, serving as chemical leads in the design of anti-AIDS agents, while thiazolo[5,4-b]acridines such as 2 provide leads in the drug design of new antitumor agents.


Quinoline antifolate thymidylate synthase inhibitors: variation of the C2- and C4-substituents. Modifications to the bicyclic ring system of the potent thymidylate synthase (TS) inhibitor N-[4-[N-[(2-amino-3,4-dihydro-4-oxo-6- quinazolinyl)methyl]-N-prop-2-ynylamino]benzoyl]-L-glutamic acid (1, CB3717) have led to the synthesis of a series of quinoline antifolates bearing a variety of substituents at the C2 and C4 positions. In general the synthetic route involved the coupling of the appropriate diethyl N-[4-(prop-2-ynylamino)benzoyl]-L-glutamate with a disubstituted 6-(bromomethyl)quinoline followed by deprotection using mild alkali. The compounds were tested as inhibitors of partially purified L1210 TS. As a measure of cytotoxicity, the compounds were tested for their inhibition of the growth of L1210 cells in culture. Good enzyme inhibition and cytotoxicity were found for compounds containing chloro, amino, or methyl substituents at the C2 position with chloro or bromo substituents at C4. The effect on enzyme inhibition of varying the N10 substituent of 2h was similar to that observed in the quinazolinone-containing antifolates, indicating that the quinoline compounds may be interacting with the enzyme in a similar way to the quinazolinones. Also, the introduction of a 2'-fluoro substituent into the benzoyl ring of several of the quinoline antifolates led to an increase in both TS inhibition and the inhibition of L1210 cell growth. These data demonstrate that the N3-H of the pyrimidine ring of the quinazolinone antifolates is not required for binding to TS if appropriate substituents are placed at the C2 and C4 positions of the bicyclic ring system.


Inhibitors of human renin with C-termini derived from amides and esters of alpha-mercaptoalkanoic acids. New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. The corresponding sulfoxide and sulfone analogues were also investigated. Some of these derivatives, including one with a stable BocPhe replacement, were relatively potent inhibitors of human plasma renin, having IC50 values below 10 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys (Macaca mulatta) at 0.06-1 mg/kg, they reduced plasma renin activity by 87-94%. However, the accompanying drop in blood pressure was of short duration.


New potent mitomycin derivatives: synthesis and antitumor activity of 7,7-(ethylenedioxy)mitomycins. A series of 6,7-dihydro-7,7-(ethylenedioxy)mitomycins was synthesized and evaluated for antitumor and anticellular activities. These compounds were prepared by basic treatment of 7-methoxymitomycins with ethylene glycol, and were structurally novel mitomycin derivatives containing a masked quinone moiety. 5,6-Enol or 6-chloro derivatives of 6,7-dihydro-7,7-(ethylenedioxy)mitomycins were also prepared and the (allyloxy)carbonyl group at the aziridine nitrogen has proved to be an efficient protecting group in chemical modification of mitomycins. Most of these mitomycin derivatives displayed potent antitumor activity against P388 leukemia in mice and anticellular activity against HeLa S3 cells.


Synthesis and anticonvulsant activity of enaminones. A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate++ + (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of greater than 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed.


N-methylated analogs of Ac[Nle28,31]CCK(26-33): synthesis, activity, and receptor selectivity. A series of singularly N-methylated analogs of Ac[Nle28,31]CCK(26-33) were synthesized by the solid-phase methodology, and their biological activity was tested in three different in vitro bioassays. The bioassays employed were the guinea pig gallbladder (GPGB), stomach (GPS), and ileum (GPI). All N-methyl analogs were agonists in all three bioassays. N-Methylation at either N- or C-terminals did not affect potency and selectivity, whereas N-methylation of internal residues [Nle28,(N-Me)Nle31]- and [Nle28,31,(N-Me)Trp30]CCK(26-33) in the sequence resulted in analogs which were 10-fold less potent than Ac[Nle28,31]CCK(26-33) in all three preparations. Different rank orders of potencies observed for [Nle28,31,Sar29]- and [Nle28,31,(N-Me)Asp32]CCK(26-33) analogs correspond to increased selectivity to either GPGB or GPS, respectively. We propose that systematic N-methylation of single amide bonds in a bioactive peptide should be conducted as an additional routine to probe structure-activity relationships.


Stereoisomers of ketoconazole: preparation and biological activity. The four stereoisomers of the antifungal agent ketoconazole (1) were prepared and evaluated for their selectivity in inhibiting a number of cytochrome P-450 enzymes. Large differences in selectivity among the isomers were observed for inhibition of the cytochromes P-450 involved in steroid biosynthesis, whereas little differences was observed for inhibition of those associated with hepatic drug metabolism. The cis-(2S,4R) isomer 2 was the most effective against rat lanosterol 14 alpha-demethylase, (2S,4R)-2 greater than (2R,4S)-4 much greater than (2R,4R)-3 = (2S,4S)-5, and progesterone 17 alpha,20-lyase, (2S,4R)-2 much greater than (2S,4S)-5 greater than (2R,4R)-3 = (2R,4S)-4, whereas the cis-(2R,4S) isomer 4 was more effective against cholesterol 7 alpha-hydroxylase, (2R,4S)-4 greater than (2S,4S)-5 greater than (2R,4R)-3, greater than (2S,4R)-2, and the trans-(2S,4S) isomer 5 was the most effective against aromatase, (2S,4R)-5 much greater than (2R,4R)-3 = (2R,4S)-4 greater than (2S,4R)-2. The cis-(2S,4R) and trans-(2R,4R) isomers 2 and 3 are equipotent in inhibiting corticoid 11 beta-hydroxylase and much more effective than their antipodes. Little selectivity was observed for inhibition of cholesterol side chain cleavage or xenobiotic hydroxylase. These data indicate that the affinity of azoles for cytochrome P-450 enzymes involved in steroid synthesis is highly dependent on the stereochemistry of the entire molecule, whereas binding to drug metabolizing enzymes is a less selective process.


Preparation and structure-activity relationships of simplified analogues of the antifungal agent cilofungin: a total synthesis approach. The echinocandins are a well-known class of lipopeptides characterized by their potent antifungal activity against Candida species. The mechanism of action of the echinocandins is generally thought to be the inhibition of beta-1,3-glucan synthesis, an important structural component in the cell wall of Candida species. Extensive structure-activity studies on the fatty acid side chain of echinocandin B (1) led to the preparation of the clinical candidate cilofungin (4). However, little is known about the cyclic peptide. We now report the preparation, by solid-phase synthesis, of a series of simplified analogs of cilofungin in which the unusual amino acids found in the echinocandins were replaced with more readily accessible natural amino acids. The solid-phase approach to the total synthesis of these analogs allowed us to conveniently explore structural modifications that could not be accomplished by chemical modification of the natural product. The simplest analog 5 showed no biological activity. Structural complexity was then returned to the system in a systematic fashion so as to reapproach the original cilofungin structure. Antifungal activity and the inhibition of beta-1,3-glucan synthesis were monitored at each step of the process, thereby revealing the basic structure-activity relationships of the amino acids and the minimal structural requirements for biological activity in the echinocandin ring system. The results suggests that the 3-hydroxy-4-methylproline residue enhances activity but the L-homotyrosine residue is crucial for both antifungal activity and the inhibition of beta-1,3-glucan synthesis.


2-Substituted 1-azabicycloalkanes, a new class of non-opiate antinociceptive agents. 2-Substituted 1-azabicycloalkanes (3- and 5-aryloctahydroindolizines 2 and 11, 3-cyclohexyloctahydroindolizine 12, 4-aryloctahydroquinolizines 13, and 3-arylhexahydropyrrolizines 14) constitute a new class of non-opiate antinociceptive agents. These compounds demonstrated activity in the mouse abdominal constriction test and many were active in the mouse tail-flick test. trans-3-(2-Bromophenyl)octahydroindolizine (2a) did not bind to the opiate receptor nor did it affect arachidonate metabolism. 3-Aryloctahydroindolizines were prepared by catalytic hydrogenation of 1-aryl-3-(2-pyridinyl)-2-propen-1-ones. The X-ray crystal structure of (-)-2a was determined and absolute stereochemistry assigned as 3-R,8a-R.


New antiinflammatory agents. 2. 5-Phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones: a new class of nonsteroidal antiinflammatory agents with potent activity like glucocorticoids. We previously described new antiinflammatory agents, 4-hydroxy-2-oxo-1-phenyl-1H-1,8-naphthyridine-3-carboxamides 1. Further modification of the compounds bearing 1-phenyl-1,8-naphthyridin-2-one as a mother skeleton led to 5-phenylimidazo[4,5-c][1,8]naphthyridin-4(5H)-one derivatives 2 and 3. Regioselective synthesis of these compounds bearing a substituent at the 1- or 3-position was conducted according to the method shown in Schemes I and II. In this series of compounds, antiinflammatory activities were greatly influenced by the position and nature of substituents on imidazole. 3-Alkyl or 3-benzyl substitution result in the potent activity, but 1-substitution did not. Minor modification of the benzyl group reduced or eliminated the activity. Detailed examination of structure-activity relationships led to 3-benzyl-5-phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (22), which exhibited potent oral antiinflammatory activities in carrageenan-, zymosan-, and reversed passive Arthus reaction-induced rat paw edemas (ED40 = 5.3, 0.37 mg/kg, ED50 = 0.47 mg/kg, respectively). This broad activity of 22 was like that of glucocorticoids. Compound 22 did not affect activities of CO and 5-LO enzymes and receptor binding of various ligands. As one of the mechanisms of action, induction of release of glucocorticoids was postulated. These results suggest that 22 represents a novel class of antiinflammatory agents.


Quenched molecular dynamics simulations of tuftsin and proposed cyclic analogues. We have used high-temperature quenched molecular dynamics calculations to investigate the conformational properties of tuftsin (Thr-Lys-Pro-Arg) in solution. Conformers obtained after quenching of the dynamical structures were sorted into families depending on their relative energies and backbone conformations. By examination of these families, several cyclic analogues of tuftsin were proposed and examined theoretically by further quenched dynamics simulations. Two of the four proposed analogues were found to adopt essentially identical conformations to that of linear tuftsin. It is suggested that these two derivatives (cyclo[Thr-Lys-Pro-Arg-Gly] and cyclo[Thr-Lys-Pro-Arg-Asp]) may be biologically active, and that the introduction of cyclic conformational constraints should help to reduce the entropic penalty to peptide binding.


Nucleosides and nucleotides. 112. 2-(1-Hexyn-1-yl)adenosine-5'-uronamides: a new entry of selective A2 adenosine receptor agonists with potent antihypertensive activity. Chemical modifications of the potent A2 adenosine receptor agonist 2-(1-hexyn-1-yl)adenosine (7, 2-HA) at the 5'-position have been carried out to find more potent and selective A2 agonists. These analogues were evaluated for adenosine A1 and A2 receptor binding affinity in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR). Among the series of compounds, 2-(1-hexyn-1-yl)adenosine-5'-N-cyclopropyluronamide (16d) had the most potent affinity to the A2 receptor with a Ki of 2.6 nM, which is essentially the same as that of the parent agonist, 2-HA. However, the most selective agonist for the A2 receptor was 2-(1-hexyn-1-yl)adenosine-5'-N-methyluronamide (16b) with a Ki of 11 nM and a 162-fold selectivity. The N-alkyl substituents of 5'-uronamide derivatives did not seem to potentiate the A2 binding affinity but drastically reduced the A1 affinity compared with the parent 2-HA. Therefore, the A1/A2 selectivity was consequently increased. Other 5'-deoxy-5'-substituted derivatives of 2-HA such as the chloro (20), carboxamide (27, 28), sulfonamide (29), urea (30), and thiourea (22) analogues were also prepared. Among these nucleosides, no active compounds with potent or selective affinities to both receptors were found except 20. Although glycosyl conformations and sugar-puckering of these nucleosides were studied by 1H NMR spectroscopy, there were no positive correlations between active and inactive agonists. 2-(1-Hexyn-1-yl)adenosine-5'-uronamide (16a) and 16d had a potent hypotensive effect at ED30 values of 0.18 and 0.17 micrograms/kg, respectively, upon iv administration to anesthetized SHR.


Alkyl and aryl neoalkanamides: highly effective insect repellents. Alkyl and aryl neoalkanamides with a total carbon number between 11 and 14, or within a molecular weight range between 185 and 227, were highly effective repellents of male German cockroaches, Blattella germanica (L.). Comparison with known repellents showed that members of this unique family of secondary amides are among the most effective and long-lasting repellents of cockroaches examined to date. In assays with females and nymphs of the German cockroach, male American cockroaches, Periplaneta americana (L.), and carpenter ant workers, Camponotus pennsylvanicus (De Geer) methyl neodecanamide, propyl neodecanamide, and methyl neotridecanamide were found highly repellent. Because of their broad spectrum of activity, longevity, and safety, these compounds, along with several other members of this family, have important applications as repellents of nuisance pests and of arthropods of public health importance.


Mechanical control of greenhead flies (Diptera: Tabanidae) in a marsh environment. The effectiveness of New Jersey box traps for the control of adult greenhead flies, Tabanus nigrovittatus, Macquart, T. conterminus Walker, was assessed at Wallops Island, Va. Trap shape and placement were tested. Shallow (0.45 m high) traps caught significantly fewer flies than cubic (0.60 m high) traps. Traps located in the inner two of four layers of traps caught fewer flies than traps in the outer layers.


Carbon dioxide released from human skin: effect of temperature and insect repellents. Measurement with an infrared analyzer of CO2 given off by the hands of human volunteers under laboratory conditions showed that they continuously produced CO2 at the rate of 1.0-1.8 ml/h. Increased production of CO2 was observed with increase in temperature for all subjects. Treatment of subjects with three insect repellents or ethanol resulted in a short-term drop in CO2 production, after which it returned to pretreatment levels. Olfactometer studies showed no correlation between the amount of CO2 produced by hands and the attractancy of the subjects to host-seeking female Ae. aegypti (L.). The supplemental addition of five times the amount of CO2 given off by the hands did not affect attractancy of subjects to mosquitoes. The amount of CO2 released by hands is negligible compared to ambient levels of 300 ppm, and it is unlikely to be attractive at this level of release by itself.


Laboratory observations on mating and leklike aggregations in Lutzomyia longipalpis (Diptera: Psychodidae). The mating behavior of the sand fly, Lutzomyia longipalpis, was studied under laboratory conditions. Male sand flies landed on the bodies of anesthetized mice, where they exhibited leklike displays such as wing fanning, parading, and aggression. Lek behavior was more frequent in older males, and dominance hierarchies were established. Male sand flies at leks copulated more frequently than male sand flies at other locations in the cage. Females mated by older males produced more eggs than did females mated by younger males; however, there was no difference in the number of larvae produced.


Seasonal abundance of Lutzomyia shannoni (Diptera: Psychodidae) on Ossabaw Island, Georgia. Population dynamics of Lutzomyia shannoni were monitored from April 1986 through December 1987 on Ossabaw Island, Ga. Most (99%) of the 19,788 adult sand flies were collected in light traps supplemented with dry ice; less than or equal to 1% were aspirated from diurnal resting sites. Adult sand flies first appeared in April and were followed by peaks of abundance during May 1986, and May and July 1987. Numbers of adults captured fell rapidly in October and November 1986 and in September and October 1987. No specimens were collected in December 1986 or in March, November, and December 1987. Light trap catch was affected positively by mean nightly air temperature and negatively by rainfall 14 d before collection, but not by wind speed or moon phase. Vesicular stomatitis viral activity, as measured by antibodies in feral and domestic swine, roughly corresponded to the seasonal appearance of adult L. shannoni during 1986 and 1987. Significantly more adults (72%) were collected in light traps at ground level (0.5m) than at heights of 4 and 8m. Most resting adults were collected from dark, moist tree holes and cavities of various hardwoods.


Differential selection of malathion resistance in Anopheles culicifacies A and B (Diptera: Culicidae) in Haryana State, India. In November 1989, for the first time after the introduction of malathion spray in 1982, increased densities of Anopheles culicifacies Giles s.l. were observed in Chhatera and Barota, two villages in Halalpur block in Sonepat District, Haryana State, India. In bioassay tests against the diagnostic dose of malathion (5% for 1 h), 41-47% of mosquitoes survived. An culicifacies populations in this area comprise two sibling species, A and B. Differential malathion resistance was observed; in species A it was 2-9% and in species B 62-66%. Likewise, species A was found to be more susceptible to DDT than was species B. The possible use of DDT spray to delay the onset of malathion resistance is discussed.


Method to estimate relative transmission efficiencies of Anopheles species (Diptera: Culicidae) in human malaria transmission. A mathematical expression was derived to estimate the relative malaria transmission efficiency of an anopheline species with respect to a standard well-characterized species for which all vector parameters can be sufficiently determined. The method is particularly useful in situations where multiple anopheline species contribute to human malaria transmission and requires the estimation of the man-biting rate, the sporozoite rate, and the human malaria incidence. Under stable conditions of vector abundance, the average sporozoite rate in a species during a transmission season would by itself reflect its relative transmission efficiency. This "efficiency" then was used to calculate the "effective human-biting rate"; i.e., the human-biting rate of that species if it were to have ecological properties identical to those of the standard species. The standard well-characterized species then could be used with the effective human-biting rate of all species to quantify transmission, thus overcoming the need to measure vector parameters for all anopheline species contributing to transmission. An expression also was derived to calculate the relative contribution made by each species to malaria transmission. The usefulness of this method was illustrated using entomological and epidemiological data from Kataragama, Sri Lanka.


Malaria transmission and vector biology on Sainte Marie Island, Madagascar. A 17-mo longitudinal malaria survey (November 1988-March 1990) was carried out on Sainte Marie Island, an area on the east coast of Madagascar which is frequently visited by tourists. During 706 man-nights of capture, 46,401 mosquitoes belonging to 32 species were caught. Sporozoite rates were determined by ELISA and incriminated Anopheles gambiae Giles s.s., An. funestus Giles, and An. mascarensis De Meillon as vectors of malaria. An. gambiae, the main vector, was highly anthropophilic but largely exophilic. Transmission by this species occurred mainly from November to April; the overall circumsporozoite antigen positivity rate was 1.7%, with a maximum of 3.2% in March-April. The nightly peak of transmission occurred between midnight and 0400 hours. The annual inoculation rate was calculated to be 100 infective bites per human, of which 92 were of Plasmodium falciparum. An. funestus played a minor role in transmission. An. mascarensis, an anopheline endemic to Madagascar, was incriminated for the first time, as a malaria vector. The sporozoite rate in this species varied from 0.4 to 0.9% as shown by both ELISA and salivary gland dissections. Parasite indices in humans up to 20 yr of age fluctuated during the year from 64 to 80%. Bed nets are recommended for malaria protection for the local population and tourists.


Diel patterns of cat flea (Siphonaptera: Pulicidae) egg and fecal deposition. The quantity of eggs and feces deposited by replicate populations of cat fleas, Ctenocephalides felis (Bouché), from domestic house cats. Felis catus, were recorded at 1-h intervals over a 24-h period, in a photoperiod of 12:12 (L:D) (photophase, 0600-1800 hours [EST]). Egg production averaged 23.96 +/- 0.83 eggs per female per day and was greatest from 2400 to 0300 hours and lowest from 0700 to 0900 hours and from 1700 to 1900 hours. Daily fecal deposition was 0.77 +/- 0.03 mg feces per flea and did not vary significantly among hours. Flea eggs and adult feces were dropped continuously from infested cats, but significantly more eggs were shed at times of day when cats normally rest. More feces are concentrated in the small areas where cats rest than over the large areas they roam. Consequently, eggs and feces would not be deposited uniformly throughout the hosts home range, resulting in a clumped distribution of larval development sites at host resting areas.