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Two cDNAs, GluClalpha and GluClbeta, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707-711, 1994). Expression studies in Xenopus oocytes showed that GluClalpha and GluClbeta have pharmacological profiles distinct from the glutamate-gated cation channels as well as the gamma-aminobutyric acid (GABA)- and glycine-gated chloride channels. Establishing the evolutionary relationship of related proteins can clarify properties and lead to predictions about their structure and function. We have cloned and determined the nucleotide sequence of the GluClalpha and GluClbeta genes. In an attempt to understand the evolutionary relationship of these channels with the members of the ligand-gated ion channel superfamily, we have performed gene structure comparisons and phylogenetic analyses of their nucleotide and predicted amino acid sequences. Gene structure comparisons reveal the presence of several intron positions that are not found in the ligand-gated ion channel superfamily, outlining their distinct evolutionary position. Phylogenetic analyses indicate that GluClalpha and GluClbeta form a monophyletic subbranch in the ligand-gated ion channel superfamily and are related to vertebrate glycine channels/receptors. Glutamate-gated chloride channels, with electrophysiological properties similar to GluClalpha and GluClbeta, have been described in insects and crustaceans, suggesting that the glutamate-gated chloride channel family may be conserved in other invertebrate species. The gene structure and phylogenetic analyses in combination with the distinct pharmacological properties demonstrate that GluClalpha and GluClbeta belong to a discrete ligand-gated ion channel family that may represent genes orthologous to the vertebrate glycine channels.

Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.

The initial goal of this study was to localize as many genes as possible that lead to syndromic and nonspecific XLMR. More recently, this goal has been redefined to include narrowing these localizations and cloning specific genes. In the last 5 years, 61 families have participated in this study; 34 have a projected or actual lod score greater than 2.0. Restudy of 12 families reported previously has been a particularly productive aspect of this study and has led to clinical redefinition and new or improved localization of most of these syndromes. Five possible new XLMR syndromes have been identified. Five large families with nonspecific XLMR have been regionally localized. Since many XLMR conditions are based on only 1 or 2 family reports, one of the major purposes of this summary is to provide clinical data on the study families so that collaborative projects can be undertaken with other centers that have similar families.

A current list of all known forms of X-linked mental retardation (XLMR) and a slightly revised classification are presented. The number of known disorders has not increased because 6 disorders have been combined based on new molecular data or on clinical grounds and only 6 newly described XLMR disorders have been reported. Of the current 105 XLMR disorders, 34 have been mapped, and 18 disorders and 1 nonspecific XLMR (FRAXE) have been cloned. The number of families with nonspecific XLMR with a LOD score of > or = 2.0 has more than doubled, with 42 (including FRAXE) now being known. a summary of the localization of presumed nonspecific mental retardation (MR) genes from well-studied X-chromosomal translocations and deletions is also included. Only 10-12 nonoverlapping loci are required to explain all localizations of nonspecific MR from both approaches. These new trends mark the beginning of a significantly improved understanding of the role of genes on the X chromosome in producing MR. Continued close collaboration between clinical and molecular investigators will be required to complete the process.

Hormone replacement should provide a serum hormone profile similar to that found in normal physiology. This is generally impractical because hormones are usually released episodically and therefore require frequent administration. However, rather than replacing the hormone directly, in theory, one could administer a mimic or amplifier of the pulse generator that controls pulsatile release of the particular hormone. Using growth hormone (GH) as a paradigm we sought such a mimetic that would provide episodic GH release when administered by the oral route. A GH secretagogue MK0677, is described that has these ideal properties; following oral administration MK0677 amplifies episodic GH release. Mechanistically, it synergizes with growth hormone releasing hormone (GHRH) through a receptor and signal transduction pathway distinct from that of GHRH and is a functional antagonist of somatostatin (SRIF). MK0677 also acts on the arcuate nucleus and appears to stimulate GHRH release. By using 35S-MK0677, a new G-protein coupled receptor for MK0677 was characterized in the plasma membrane fraction of pituitary and hypothalamic tissue. The receptor is present in very low abundance and couples to phospholipase C. Other ligands selective for this receptor also cause synchronization of well-defined pathways leading to GH release. Repeated oral treatment of dogs once daily with MK0677 initiates amplified pulsatile GH release accompanied by increases in IGF-1 that are sustained. The unique biological properties of MK0677 and other synthetic ligands that bind to the same receptor force us to predict that these ligands mimic a naturally occurring hormone that regulates pulsatile GH release. Understanding the regulatory mechanisms involved in this paradigm has broad implications for the control of pulsatile rhythms in the endocrine system.

In this chapter we summarize the available data on a novel class of ligand-gated anion channels that are gated by the neurotransmitter glutamate. Glutamate is classically thought to be a stimulatory neurotransmitter, however, studies in invertebrates have proven that glutamate also functions as an inhibitory ligand. The bulk of studies conducted in vivo have been on insects and crustaceans, where glutamate was first postulated to act on H-receptors resulting in a hyperpolarizing response to glutamate. Recently, glutamate-gated chloride channels have been cloned from several nematodes and Drosophila. The pharmacology and electrophysiological properties of these channels have been studied by expression in Xenopus oocytes. Studies on the cloned channels demonstrate that the invertebrate glutamate-gated chloride channels are the H-receptors and represent important targets for the antiparasitic avermectins.

This study is the first systematic examination of a trapezius EMG biofeedback training regimen with tension headache sufferers. It evaluated the differential effects of three psychophysiological treatments for tension headache: (1) a standard 12-session frontal EMG biofeedback training regimen (n = 8), (2) a 12-session upper trapezius EMG biofeedback training regimen (n = 10), and (3) a standard seven-session progressive muscle relaxation therapy regimen (n = 8). Posttreatment assessment at 3 months following cessation of treatment revealed clinically significant decreases in overall headache activity (50% or greater) in 50% of subjects in the frontal biofeedback group, 100% in the trapezius biofeedback group, and 37.5% in the relaxation therapy group. Chi-squared analyses indicated that the trapezius biofeedback group was more effective in obtaining significant clinical improvement than the frontal biofeedback and relaxation therapy groups (which did not differ from each other). The three treatments did not differ on secondary measures of headache improvement (number of headache-free days, peak headache activity, and medication index). Implications for the psychophysiological treatment of tension headache, as well as future research directions, are discussed.

Xenopus laevis oocytes were injected with mRNA isolated from the free-living nematode Caenorhabditis elegans and the activation and potentiation of a glutamate-sensitive chloride current by a series of avermectin analogs and milbemycin D were determined. There was a strong correlation between the EC50 value determined for current activation in oocytes, the LD95 value for nematocidal activity, and also for the Ki value determined in a [3H]ivermectin competition binding assay. Four of the analogs were tested for potentiation of glutamate-sensitive current and the rank order for potentiation correlated with the EC50 for direct activation of current. We conclude that avermectins and milbemycins mediate their nematocidal effects on C. elegans via an interaction with a common receptor molecule, glutamate-gated chloride channels.

This study examined the temporal stability of three psychophysiological responses (frontal electromyographic activity, hand surface temperature, and heart rate) recorded over four sessions (days 1, 2, 8, and 28) on 34 subjects, 17 with high Spielberger Trait Anxiety Inventory scores and 17 with low scores. Each session consisted of a 20-minute adaptation period, a baseline condition, and two stressors (one cognitive, the other physical). Two forms of reliability coefficients were employed, intraclass correlations and Pearson Product Moment; the two types of reliability coefficients arrived at the same conclusions. Results indicated that reliability coefficients for the two anxiety groups did not differ on frontal EMG or heart rate responses; however, hand surface temperature responding was considerably less reliable for high anxious individuals than low anxious individuals. Reliability coefficients on absolute scores were, for the most part, reliable. Treating the responses as relative measures (percent change from baseline or simple change scores from baseline) produced smaller and less reliable coefficients. Magnitudes of the three physiological responses did not significantly differ as a function of high or low trait anxiety. Findings are discussed in terms of their clinical, as well as basic psychophysiological, importance.

This is a re-analysis of data from a previous study which examined the temporal stability of three psychophysiological responses [frontal electromyographic activity (EMG), hand surface temperature, and heart rate]. Each response was recorded on 64 subjects over four sessions, each of which consisted of a 20-min, adaptation period, a baseline condition, and two stressors (one cognitive, the other physical). Rather than using Pearson product-moment correlations, as nearly all psychophysiological test-retest reliability studies have, we have now analyzed the data using intraclass correlation coefficients. This type of correlation allows one to incorporate more than two test-retest values on the same subjects. Analysis indicated that, with the exception of EMG during the physical stressor, the absolute values of the responses had quite significant reliability (.70 or greater). Treating the responses as relative measures (percent change from baseline or simple change scores from baseline) produced smaller and frequently less stable coefficients. It is concluded that statistical estimates of psychophysiological response reliability are functions of the design and particular reliability analysis employed.

High affinity avermectin binding sites have been identified and partially characterized in membranes from two insect species, Drosophila melanogaster and the locus Schistocerca americana. There is a 10-fold increase in the density of ivermectin binding sites associated with membranes isolated from Drosophila heads (a neuronally enriched tissue source) compared to the bodies (Bmax values were 3.5 and 0.22 pmol/mg, respectively) with only a small difference in the apparent dissociation constant (Kd values of 0.20 and 0.34 nM for heads and bodies, respectively). Membranes prepared from metathoracic ganglia of the locust, Schistocerca americana, were highly enriched in high affinity avermectin binding sites (Kd = 0.2 nM and Bmax = 42 pmol/mg). Using an [125I]arylazido-avermectin analog as a photoaffinity probe, a 45 kDa protein was identified in both the Drosophila head and body tissue preparations. A 45 kDa protein was also specifically labeled with [125I]azido-avermectin in the locust neuronal membranes.

The avermectins are a family of macrocyclic lactones used in the control of nematode and arthropod parasites. Ivermectin (22,23-dihydroavermectin B1a) is widely used as an anthelmintic in veterinary medicine and is used to treat onchocerciasis or river blindness in humans. Abamectin (avermectin B1a) is a miticide and insecticide used in crop protection. Avermectins interact with vertebrate and invertebrate GABA receptors and invertebrate glutamate-gated chloride channels. The soil nematode Caenorhabditis elegans has served as a useful model to study the mechanism of action of avermectins. A C. elegans messenger RNA expressed in Xenopus oocytes encodes an avermectin-sensitive glutamate-gated chloride channel. To elucidate the structure and properties of this channel, we used Xenopus oocytes for expression cloning of two functional complementary DNAs encoding an avermectin-sensitive glutamate-gated chloride channel. We find that the electrophysiological and structural properties of these proteins indicate that they are new members of the ligand-gated ion channel superfamily.

It has recently been shown that Xenopus oocytes injected with mRNA from the free-living nematode Caenorhabditis elegans express avermectin-sensitive chloride channels. Joseph Arena here reviews what is known about the mechanism of action of avermectin and how these recent results relate to the mechanism in nematodes.

Membrane currents were recorded from Xenopus laevis oocytes injected with C. elegans poly(A)+ RNA. In such oocytes glutamate activated an inward membrane current that desensitized in the continued presence of glutamate. Glutamate-receptor agonists quisqualate, kainate, and N-methyl-D-aspartate were inactive. The reversal potential of the glutamate-sensitive current was -22 mV, and exhibited a strong dependence on external chloride with a 48 mV change for a 10-fold change in chloride. The chloride channel blockers flufenamate and picrotoxin inhibited the glutamate-sensitive current. Ibotenate, a structural analog of glutamate, also activated a picrotoxin-sensitive chloride current. Ibotenate was inactive when current was partially desensitized with glutamate, and the responses to low concentrations of glutamate and ibotenate were additive. The anthelmintic/insecticide compound avermectin directly activated the glutamate-sensitive current. In addition, avermectin increased the response to submaximal concentrations of glutamate, shifted the glutamate concentration-response curve to lower concentrations, and slowed the desensitization of glutamate-sensitive current. We propose that the glutamate-sensitive chloride current and the avermectin-sensitive chloride current are mediated via the same channel.

These studies describe the effect of protein kinase C (PKC) activation on the activity of voltage-sensitive L-type Ca2+ channels of GH3 pituitary cells. The rate of 45Ca2+ uptake was stimulated greater than 25-fold by depolarization in the presence of BAY K 8644; the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) reduced this response by 70% in a concentration-dependent fashion. Phorbol 12,13-dibutyrate (PDBu) inhibited depolarization-induced 45Ca2+ uptake within 1 min and caused a nearly maximal reduction after 1 h; its effects were rapidly reversible. TPA decreased the high K(+)-stimulated increase in intracellular free calcium ion concentration ([Ca2+]i) from 8.5- to 3.2-fold by 5 min and to 2.0-fold after 18 h without altering the peak [Ca2+]i response to the peptide hormone TRH. Ca2+ channel current, measured directly using the whole cell configuration of the patch-clamp technique, declined an average of 6.4% over 5 min for control cells and 28.9% when TPA was added to the bathing medium for 5 min. Treatment with 100 nM TPA for 24 h dramatically reduced peak current without shifting the peak of the current-voltage relationship. The mean peak Ca2+ channel current was reduced from 423 to 128 pA, although a few cells seemed completely resistant. To determine whether the effects of phorbol esters were due to the activation of PKC we tested the potency of several drugs to inhibit L-channel activity and to shift the affinity of the epidermal growth factor (EGF) receptor, an established PKC response.(ABSTRACT TRUNCATED AT 250 WORDS)

We report on a family with X-linked mental retardation (XLMR) and severe spastic paraplegia. Appearance is normal but there is severe involvement of the lower limbs (affected relatives never walked), with minimal involvement of the upper limbs and unusual MRI findings including macrogyria, white matter hypoplasia, lack of myelination and a markedly increased paramagnetic signal suggestive of iron deposition. Linkage studies documented possible linkage, with no recombination, between the disease locus and DXS424. A 7-point linkage analysis yielded a maximum LOD score of 1.9, (theta = 0.00) for three loci spanning Xq22-q25. The combination of the unusual clinical and MRI findings and the tentative localization to a region different than other XLMR syndromes with spastic paraplegia, provide good evidence that this is a new XLMR syndrome.

We restudied a family with X-linked mental retardation (XLMR) originally reported in abstract form by Davis et al. [1981]. All 8 living affected males were examined. Characteristics included severe mental retardation, spastic paraplegia, dysarthria, muscle wasting, scoliosis, broad shallow pectus excavatum, long face, large ears with minor modeling anomalies, foot deformities, joint contractures, and neck drop. Stature, OFC, testicular volume, high resolution chromosome and fragile X studies, and plasma amino acids were all normal. Their manifestations closely resemble those of a large family with XLMR originally reported by Allan et al. [1944] and restudied by Stevenson et al. [1990]. This condition has been termed the Allan-Herndon-Dudley syndrome (AHDS). As AHDS has been mapped to Xq21, mapping studies were undertaken to determine if this family maps to the same location. These studies demonstrate tight linkage to Xq21, with a maximum lod score of 2.88 obtained with probe pX65H7 (DXS72). Multipoint analysis located the mutant gene quite close to pX65H7 (multipoint Z = 4.14), slightly more proximal in Xq21 than was suggested by the data from the original AHDS family. It appears likely that this family is the second reported family with AHDS.

This study evaluated the effects of a 12-session frontal electromyographic biofeedback training regimen on the headache activity of eight tension headache sufferers aged 62 and older. The biofeedback sessions were slightly modified for a geriatric population, essentially to increase comprehension and retention of rationale and instructions. Post-treatment assessment at three months revealed significant decreases in overall headache activity (50% or greater) in 50% of the subjects, and moderate improvement (35%-45%) in three of the remaining four subjects. Significant clinical and/or statistical pre-post differences were also found for the number of headache-free days, peak headache activity, and medication index. This is the first prospective study of biofeedback training for tension headache in an elderly population and, unlike previous retrospective studies, suggests that such therapy may be an effective intervention in the treatment of tension headaches in the elderly.

We have studied block of L-type calcium channels by intracellular and extracellular application of the ionized dihydropyridine derivatives amlodipine and SDZ 207-180. We find that extracellular application of either drug causes voltage-dependent block of calcium channels. However, neither drug is effective when applied intracellularly. The insensitivity of calcium channels to intracellular drug is not due to the low concentrations of cytosolic calcium, because voltage-dependent block by ionized amlodipine, SDZ 207-180, and the neutral drug nisoldipine persists under conditions in which Ca0 is buffered by EGTA. In fact, the time course of the development of block by the ionized but not neutral drug molecules studied, is slower in the presence than in the absence of calcium. Our results indicate that the DHP binding site of the L-type calcium channel is close to the extracellular surface of the cell membrane and that ionized DHP molecules may interact with the receptor in a manner that is uniquely affected by calcium.

We have developed an ambulatory recorder capable of monitoring low back muscle tension, trunk motion, and ratings of pain and fatigue. It weighs 22 ounces, fits into a canteen belt, and records every second for 18 hours. Eleven subjects wore the recorder during all walking hours for between 3 and 5 days. Six subjects had chronic low back pain due to muscle tension, three experienced low back pain after labor, and two had no pain. Movement and muscle tension correlated highly when subjects were pain free but not when they were in pain. Muscle tension increased before pain was experienced.

When the patch-clamp technique was used, a slowly activating, time-dependent outward current was identified in both cell-attached and excised membrane patches obtained from guinea pig ventricular myocytes. This macroscopic patch current was present in approximately 50% of patches studied and could be observed both in the presence and absence of unitary single channel activity (i.e., ATP-sensitive K+ channels). The time course of activation of the patch current resembled that of the whole cell delayed-rectifier K+ current (IK) recorded under similar ionic conditions, and the patch current and IK were activated over a similar membrane potential range. The time-dependent patch current could be eliminated when the Nernst potential for K+ equaled that of the pulse voltage. The patch current was inhibited by external addition of the tertiary ammonium compound LY 97241 (50 microM) and was augmented after internal application of the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (500 nM). Deactivating tail currents with kinetics similar to those of IK could be recorded to cell-attached and excised patches. Unitary single channel events underlying the time-dependent patch current could not be resolved despite various attempts to increase single channel conductance. Thus our results suggest that a major component of delayed rectification in guinea pig ventricular cells is due to the activity of a high-density, extremely low conductance K+ channel.

Photographs of normal and abnormal relatives with X-linked mental retardation (XLMR) and clinical data are combined in a Macintosh II computer system to provide an objective and versatile means of evaluating developmental abnormalities. The system includes a flatbed scanner for the entry of photographs and text, additional memory to enhance resolution of photographs, and several programs which facilitate searches for keywords. The primary advantages of the system include an easy interaction between descriptive words and photographs, and rapid comparison of whole faces and specific traits from many individuals. Information within families and between disorders can easily be compared in coded or uncoded fashion. Data from the 34 currently described syndromes emerging from the category of "non-specific XLMR" are being used to develop and test this approach. Neither standard photographs nor most computerized diagnostic systems permit this flexibility. Ultimately, this approach will provide a valuable diagnostic and teaching aid.

This paper presents the results of two studies. In the first, 20 tension headache subjects were evaluated in both a headache and non-headache state on bilateral trapezius and unilateral frontalis electromyographic activity during six positions: standing, bending from the waist, rising, sitting with back unsupported, sitting with back supported, and prone. Results indicated no effect of headache state on either measure. In a second study, 11 of the tension headache sufferers in Study One and 11 age-matched controls were compared on the same measures (controls were assessed two times, with a one-week duration separating evaluations). Results indicated a diagnosis by position interaction, with post-hoc tests revealing the muscle activity of tension headache sufferers to be considerably higher during the prone position than that of non-headache controls. Non-significant trends were found when examining the data for clinically significant abnormalities (90% of the headache sufferers were found to have significant clinical abnormalities).

This paper presents the results of two studies in which bilateral surface EMG recordings of paraspinal muscle tension were measured in 29 lower back pain and 20 normal subjects in 6 different positions (standing, bending from the waist, rising, sitting with back supported, sitting unsupported, prone) on two occasions, and a comparison of the data from both studies. Measures were highly reliable when examined using analysis of variance procedures. Statistically significant reliability coefficients were obtained when the absolute values of the measures were examined, although in some instances less than 20% of the variance was explained. When examined as relative [percent change from baseline (prone) condition] values, differences between the two groups were observed: the normals were statistically more reliable than lower back pain subjects during every condition. Implications for clinical work and both basic and applied research are discussed.

The results with the K+ channel blocking compounds are encouraging because they show a slight structural change in a parent blocking compound can dramatically alter the type of K+ channel blocked by a drug. Our work continues in an effort to determine a more detailed relationship between structural features of a blocker and the type of K+ channel effected. We hope to be able to reveal the requirements for potent and specific blockers of each of these channel types. Selective blockade of these, and other, K+ channels in heart and smooth muscle cells, a goal suggested by the preliminary results presented here, may provide useful tools for more detailed studies of K+ channels. Our experiments also show that temperature can be used to separate the beta-adrenergic regulation of ICa and IDR suggesting different modulatory mechanisms. The results with forskolin show this separation exists at the level of elevated cAMP. This suggests that the K+ and Ca++ channel proteins may be phosphorylated by the same cAMP-dependent protein kinase but with different temperature-sensitive kinetics. It will be interesting to see if this temperature-sensitivity extends to phosphorylation of the channel during intracellular application of cAMP-dependent protein kinase.

This study reports the results of the first investigation into the relationship between situational stress and phantom limb pain. Twenty-seven male amputees recorded their pain and overall stress levels daily for 180 days using a 1-10 rating scale. Three possible relationships into the etiology and/or maintenance of phantom limb pain were examined using cross-lagged correlational techniques: an isomorphic relationship (same time increases in pain lead to same time increases in stress and vice versa), a consequence relationship (increases in pain precede increases in stress), and a precursor relationship (increases in stress precede increases in pain). Thirty-seven per cent of subjects demonstrated some significant precursor relationship. Although support was found for all three hypotheses, the most frequently observed relationship was the isomorphic one. Seventy-four per cent of subjects demonstrated some significant stress-pain relationship. The results lend support to the psychological theory underlying the use of psychophysiological interventions such as biofeedback and relaxation therapy in amputees with phantom limb pain.

Changes in pH0 were used to to vary the ratio of neutral to ionized amlodipine (acid dissociation constant = 10(-8.6). The behavior of neutral and charged drug blockade of calcium channel current (ICa) was tested in the context of the modulated receptor hypothesis. ICa was recorded at room temperature from enzymatically isolated guinea pig ventricular cells using the whole-cell arrangement of the patch-clamp technique. When amlodipine was predominantly charged (pH0 = 7.4), trains of pulses that induced multiple channel openings enhanced block, but inhibition of ICa was also promoted by depolarizing changes in holding potential. Neutral amlodipine (pH0 = 10.0), blocked ICa at depolarized membrane potentials without channel openings. This form of the drug resembled other previously described neutral dihydropyridine (DHP) blockers in its voltage dependence. Recovery from block by ionized drug molecules was very slow and incomplete, whereas block by neutral molecules was always reversible at hyperpolarized membrane potentials. We conclude that amlodipine, like other DHP calcium channel blockers, preferentially blocks calcium channels in depolarized cells. At pH0 7.4 amlodipine molecules gain access to the DHP receptor more readily when channels open, but channel openings are not required for this interaction. Recovery from block by ionized drug is almost irreversible, suggesting that channel openings are needed for this process or that the ionized drug stabilizes the calcium channel in a nonconducting state.

When Oliver Wendell Holmes wrote "To guard is better than to heal, the shield is nobler than the spear!" he must have had in mind the origin, many years later, of the poison control center movement. In 1952, the American Academy of Pediatrics (AAP), through a survey by its newly appointed Committee on Accident Prevention, found that the most common medical emergency in children was poisoning. The study brought forth many requests for up-to-date information on toxic ingredients in household products, as well as for improved therapeutic measures. This gave impetus to the development and implementation of poison control centers in the United States, an endeavor practically all-pediatric oriented. Then, the development of safety closures and packaging and the Poison Prevention Packaging Act in 1970 rapidly followed. This is a historical account of the AAP's role and the combined efforts of practicing and academic pediatricians in a mid-20th century movement that has saved countless children's lives.

The present study examined the psychological test responses of 99 headache sufferers and 30 matched nonheadache controls. Headache subjects were of four types: migraine (n = 26), muscle contraction (n = 39), combined migraine-muscle contract ion (n = 22), and cluster (n = 12). Measures consisted of the Minnesota Multiphasic Personality Inventory, a modified hostility scale derived from the MMPI, Back Depression Inventory, State-Trait Anxiety Inventory, Autonomic Perception Questionnaire, Rathus Assertiveness Schedule, Social Readjustment Rating Scale, Psychosomatic Symptom Checklist, Schalling-Sifneos Scale, Need for Achievement, and Hostile Press. Significant differences were found on five clinical scales of the MMPI--1, 2, 3, 6, and 7. Of the non-MMPI scales, only the Psychosomatic Symptom Checklist and Trait Anxiety Inventory were significant. Control subjects revealed no significant findings on any tests. The headache groups fell along a continuum, beginning with cluster subjects, who showed only minimal distress, continuing through migraine and combined migraine-muscle contraction, and ending with muscle contraction subjects, who revealed the greatest degree of psychological disturbance. However, none of the headache groups could be characterized by marked elevations on any of the psychological tests, which contrasts with past research findings. It is suggested that the present results may be more representative of the "typical" headache sufferer.

The Psychosomatic Symptom Checklist (PSC), a questionnaire assessing psychosomatic symptoms, was administered to two separate samples of college students. For Sample 1 (N = 698), the questionnaire was readministered to three separate subsets at intervals of either 1 week (N = 143), 4 weeks (N = 74), or 8 weeks (N = 48). Each subset of subjects recompleted the PSC on only one of the three retest intervals. Based on the initial administration an analysis of the normative data revealed a mean total score of 23.7, suggesting a relatively low degree of psychosomatic symptoms in this group. Although total scores decreased slightly over time, test-retest correlations remained high (r greater than 0.80, P less than 0.0001). Individual item correlations was greater than r = 0.50 throughout. Sample 2 (N = 249) completed the PSC, Beck Depression Assertiveness Scale (RAS), and intercorrelations were computed between these measures. This analysis revealed little overlap between the psychosomatic complaints assessed by the PSC and other commonly used measures of psychological distress. Finally, a factor analysis revealed one major factor on which all but 2 of the 17 questionnaire items loaded significantly. These results suggest that the PSC is sensitive to psychosomatic distress and remains reliable over time.

Four studies were conducted on a sample of 230 undergraduates to determine the psychometric properties of a measure of alexithymia, the Schalling-Sifneos Scale. In the first study it was found that scores on the scale are approximately normally distributed for each sex with 8.2% of males and 1.8% of females in the alexithymia range. In the second study a factor analysis of the scale revealed three distinct factors: (1) 'difficulty in expression of feelings'; (2) 'the importance of feelings especially about people'; (3) 'day-dreaming or introspection'. In the second factor analytic study, scores from several standard psychological tests on the same subjects were introduced with the scale items. Two factors in this analysis were comprised almost entirely of the other test scores: a 'general psychological distress factor' and a 'concerns about physical symptoms factor'. The other two factors were similar to factors 1 and 2 above in terms of items. The Rathus Assertiveness Scale loaded positively on the equivalent of factor 1. In the lst study, it was shown that Schalling-Sifneos Scale score is relatively orthogonal to other psychological tests with the exception of a Psychosomatic Symptom Checklist and thus is measuring something other than depression, anxiety, etc.

Real time ultrasonography is a diagnostic technique very widely used in pediatrics and with specific applications in neonatology. Bedside its use in Neonatal I.C.U. it has many interesting aspects for intraabdominal and intracranial pathology. In some particular conditions this procedure can be the first diagnostic tool. Conventional X-rays can be performed after sonographic data have been analyzed.

The omphalosite monster is acardiac (deprived of heart) and his survival is only possible through intrauterine life because of the umbilical vascular connections with his healthy monochorionic twin brother who takes in charge the circulation of both. We report one typical case of the acephalic variety in which all structures derived from the fetal cephalic fold were absent. Its only eventual clinical interest is limited to the prenatal radiological diagnosis and the neonatal onset of congestive heart failure in the healthy twin, a fact which must be known in order to establish an early treatment. On this occasion, we briefly review the current knowledge about this very rare form of monstrosity.

The electrophysiologic properties of amlodipine in single guinea-pig ventricular cells were investigated. The degree of ionization of the drug molecule was found to affect both the development of and the recovery from block of L-type calcium channels. Under alkaline conditions, when most of the drug is in a neutral form, the actions of amlodipine resemble previously described neutral dihydropyridine (DHP) compounds. Under these conditions, calcium channel block by amlodipine is reversibly regulated by cell membrane potential, i.e., block is more pronounced at voltages positive to -50 mV and completely relieved at voltages negative to -80 mV. When the drug molecule is ionized, block develops very slowly at positive membrane potentials and is very difficult to relieve on returning the membrane potential to more negative voltages. It is concluded that the degree of ionization of the drug molecule limits access to the DHP receptor and that the drug-bound receptor can be titrated by extracellular hydrogen ions. These results place limitations on the location of the DHP receptor within the cardiac sarcolemmal membrane.