Unrelenting Depression and Suicidality in Women with Autistic Traits.

Understanding the cognitive and emotional mechanisms that link autistic traits and risk for suicide is a vital next step for research and clinical practice. This study included a broad sample of adult women (n = 74) who report finding social situations confusing and/or exhausting, and who score high on measures of autistic traits. Regardless of autism diagnostic status, these women reported high rates of suicidal thoughts and behaviors. Depression symptoms were more associated with suicidality than were autistic trait measures of social communication. Measures of neurotypical "imagination" and of repetitive behavior likewise were associated with suicidality risk. Simultaneously feeling sad and feeling stuck or unable to imagine alternate strategies, may uniquely increase suicide risk in autism.

Immunotherapy with Mycobacterium vaccae and peripheral blood flow in long-treated leprosy patients, a randomised, placebo-controlled trial.

OBJECTIVE: to evaluate immunotherapy as a means of improving peripheral blood flow in chronic leprosy patients. DESIGN: this was a double-blind, randomised, placebo-controlled, clinical trial. MATERIALS: heat-killed Mycobacterium vaccae 1mg plus 0.02 microg Tuberculin protein per 0.1 ml dose in borate buffer, with saline as placebo. Those studied were 92 long-treated residents of a leprosy centre in Iran, 10 of their healthy children and 10 staff members. Evaluation employed the Perimed PF2, Laser-Doppler Flowmeter, a platinum skin thermistor, and a thermal sensibility tester. METHODS: single intradermal injections of test or placebo were given to 103 patients 18 months before the blinded evaluation. Fingerpulp blood flux was measured in controlled conditions and vasomotor reflexes and skin sensation to touch, pain and heat were evaluated in 45 and 47 patients in the placebo and M. vaccae groups, respectively, and in 20 healthy control persons. RESULTS: Laser-Doppler flux, skin temperature, vasomotor reflexes and sensation were impaired in leprosy patients. Immunotherapy improved (p < 0.05) Laser-Doppler flux, skin temperature and temperature sensation. CONCLUSIONS: immunotherapy, given 18 months earlier, significantly improved blood flow and temperature sensation, in fully-treated, chronic, leprosy patients. The same principles might be employed in other conditions of reduced peripheral blood flow.

Dysfunctional beliefs discriminate personality disorders.

This study examines whether specific sets of dysfunctional beliefs are differentially associated with five personality disorders (PDs) as predicted by cognitive theory. Seven hundred fifty-six psychiatric outpatients completed the Personality Belief Questionnaire (PBQ) at intake and were assessed for PDs using a standardized clinical interview conducted by assessors who were blind to patients' PBQ responses. Findings showed that patients with avoidant, dependent, obsessive-compulsive, narcissistic, and paranoid PDs preferentially endorsed PBQ beliefs theoretically linked to their specific disorders. The study results support the cognitive theory of personality disorders. Suggestions are made regarding the clinical utility of the PBQ with personality-disordered patients and future research on the PBQ.

Evidence for sodium-coupled acid-base transport across the basolateral membrane of the reabsorptive duct of the human eccrine sweat gland.

Intracellular pH was measured in isolated nonperfused ducts of human eccrine sweat glands in vitro to investigate basolateral acid-base transport mechanisms. Bath sodium removal led to a bicarbonate-independent, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid insensitive acidification. The recovery of this acidification was ethylisopropyl amiloride sensitive, suggestive of basolateral sodium:hydrogen exchange. Whereas bath chloride removal led to a small acidification this was not 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid sensitive and its causes remain unclear. Elevation of bath potassium to depolarize the basolateral membrane led to a small alkalinization but this was not mimicked by addition of barium or chloride removal. As chloride removal and barium addition would be expected to cause larger depolarizations than potassium elevation these observations do not support a major role for electrogenic acid-base transport. In conclusion, although this study does not support a major role for electrogenic acid-base transport, it has demonstrated the basolateral presence of sodium-coupled acid-base transport in the reabsorptive duct of the human eccrine sweat gland, which most likely represents a sodium:hydrogen exchanger involved in regulation of intracellular pH.

Evidence for the construct validities of the Beck Youth Inventories with child psychiatric outpatients.

To provide further information about the construct validities of the Beck Youth Inventories of Emotional and Social Impairment, these inventories were administered to 35 female and 65 male outpatients whose ages ranged from 7 to 12 years and who were diagnosed with various psychiatric disorders. The Children's Depression Inventory was also administered, and the children were rated by a parent with the Conners' Parent Rating Scale-Revised: Short Form. The scores on the former inventory were more positively correlated with the scores on the Beck Youth Depression Inventory (r =.81, p<.001) than with scores on the four other Beck Youth Inventories, and those on the Conners Oppositional scale were comparably correlated with the scores on the Beck Youth Disruptive Behavior (r=.49, p<.001) and Anger (r=.41, p<.001) Inventories. These latter correlations were higher than those for scores on the Oppositional scale with the scores on the three other Beck scales.

Depression.

Depression occurs in up to 45% of medically hospitalized older patients. The diagnosis of depression in this population is particularly difficult. Assessing for depression is made easier by the use of scales for screening and is best accomplished using the inclusive approach. These depressions can be divided into two groups: "reactive" depression and major depression. Depression is treatable using a variety of modalities that include psychotherapy, pharmacotherapy, and electroconvulsive therapy.

Complex cognitive therapy treatment for personality disorder patients.

Preliminary studies have found cognitive therapy to be a promising treatment for personality disorder patients. Therapy is based on an individualized formulation of the case and is generally much more complex and potentially more lengthy than the treatment for patients with Axis I disorders alone. Modifications of treatment include a greater focus on the therapeutic relationship, increased emphasis on developmental events, variations in session structure, and utilization of specialized strategies to alter dysfunctional beliefs and compensatory behavioral strategies.

A comparison of focused and standard cognitive therapy for panic disorder.

The relative efficacy of two psychotherapeutic approaches to panic disorder, namely, focused cognitive therapy (FCT) and standard cognitive therapy (SCT) was examined. FCT focused specifically on the "catastrophic misinterpretation" of physical and psychological sensations experienced during panic attacks induced in the office or occurring spontaneously between sessions. SCT focused primarily on the cognitions and beliefs relevant to interpersonal concerns involved in generalized anxiety. We hypothesized that FCT would be more effective than SCT since the latter did not include an induced panic exercise (exposure condition) specific to the patient's panicogenic cognitions. Forty patients diagnosed with panic disorder were randomly assigned to the SCT and FCT groups for approximately 12 to 18 sessions of treatment. Both groups reported significant decreases in the severity of the clinical measures at termination. Moreover, 89.5% of the SCT group and 84.2% of the FCT group were free of panic attacks at 1-year follow-up. Contrary to the predictions, the results for measures of panic attack frequency, anxiety, and depression did not reveal any significant differences between the two groups. Results suggest that in-office "exposure" is not necessary for improvement and that a primary focus on cognitions associated with generalized anxiety may be an effective intervention. However, since improvement in panic was correlated with normalizing of panic-related beliefs in both conditions, it is suggested that cognitive change may be a crucial ingredient of improvement in panic episodes.

Identification of a complex congenital heart defect susceptibility locus by using DNA pooling and shared segment analysis.

The identification of genetic loci involved in most forms of congenital heart disease has been hampered by the complex inheritance patterns of these disorders. Atrioventricular canal defects (AVCDs) are most commonly associated with Down syndrome, although non-syndromic cases also occur. Non-syndromic AVCDs have been attributed to multifactorial inheritance. However, the occurrence of a few kindreds with multiple affected individuals has suggested that a major genetic locus can account for the disorder in some families. We have used a combination of DNA pooling and shared segment analysis to perform a high density screen of the entire autosomal human genome in an extended kindred. In so doing, we have identified a genetic locus on chromosome 1 shared by all affected individuals. Our data demonstrate the existence of a congenital heart defect susceptibility gene, inherited as an autosomal dominant with incomplete penetrance, involved in AVCD. Furthermore, our data demonstrate the power of using key isolated kindreds in combination with high density genomic screens to identify loci involved in complex disorders such as congenital heart defects.

Sympathetic vasomotor dysfunction in leprosy patients: comparison with electrophysiological measurement and qualitative sensation testing.

Testing of skin vasomotor reflexes (VRs) by laser Doppler flowmetry (LDF) is now a recognised method of measuring peripheral dysautonomia. To assess its specificity as an indicator of impairment to unmyelinated autonomic fibres, VR testing at the fingerpulp was compared with standard qualitative sensation (QST) and with sensory electrophysiological (SNVC) measurements in 39 Iranian leprosy patients. There was a significant relationship between VR and SNCV values (but not QST): these were jointly measurable in 38.5% of fingers, and jointly absent in 35.3% of fingers which also showed significantly reduced LDF perfusion and skin temperatures. However, in 10.3% of fingers, predominantly index and otherwise apparently healthy, VRs were absent but SNCV present, suggesting early sub-clinical autonomic impairment. In a further 16% of fingers, predominantly ulnar and with poor microcirculation, intact (though impaired) VRs could be recorded despite the absence of SNCV responses, suggesting sparing or regeneration of these fibres. This evidence suggests that where there is heterogeneity of nerve damage a combination of VR and electrophysiological testing can indicate the functional status of distinct fibre types.

Perfusión Doppler con laser ionfrarrojo y cercano al rojo en manos de pacientes de lepra en España

Se ha empleado una nueva técnica de perfusión Doppler con láser a las longitudes de onda, rojo (663 nm) y cercano al rojo (780 nm) para obtener imágenes del flçujo sanguíneo de los dedos de pacientes de lepra y vonluntarios sanos en el Sanatorio de Fontilles. La técnica permite medir el flujo en las estructuras dérmicas y subdérmicas y podría ser útil para localizar deterioro microcirculatorio. Se pueden medir niveles muy elevados de riego en la pulpa de los dedos a la temperatura ambiente de Fontilles (23-6.ºC), ya debido a una abundante anastomosis arteriovenosa, desempeñan un papel termorregulador. Sin embargo en muchos pacientes, incluyendo los que no presentan un compromiso clínico en las manos, el riego sanguíneo y temperaturas cutáneas estaban significativamente reducidas, confirmando hallazgos previos en pacientes de lepra en India e Iran. Los hallazgos preliminares indican que estas disminuciones de riego no están localizadas a una región anatómica pero pueden afectar todos los dedos evaluados de un individuo sugiriendo un deterioro más generalizado de la función termoregulatoria. Mientras que esto puede implicar un mecanismo central, también se podría explicar por una vasculitis sub-cutánea continua de los dedos. Nuestros trabajos anteriores indicando una asociación entre pérdida de sensación y reducción del flujo sanguíneo, también sugieren factopres neurales como una depleción de neuropéptidos sensorilaes.

Interaction between adrenergic agonists and forskolin on adenylate cyclase activity in the rabbit proximal tubule.

Using a micro-radioimmunoassay, cAMP was measured in single, isolated S2 proximal straight tubules dissected from rabbit kidneys to investigate the effects of adrenergic agonists on adenylate cyclase activity. The baseline activity of adenylate cyclase was low and unaffected by either the alpha 2 agonist clonidine, the beta agonist isoprenaline (in the absence or presence of 1 microM forskolin) or 1 microM forskolin. Adenylate cyclase activity was markedly stimulated by 20 microM forskolin, an effect which was inhibited by 1 microM clonidine. The inhibition by clonidine was not apparent in the presence of the alpha 2 antagonist yohimbine. These results confirm the inability of isoprenaline to stimulate adenylate cyclase in the rabbit proximal tubule and demonstrate the coupling of alpha 2 receptors, in an inhibitory fashion, to adenylate cyclase. The inhibitory action of the alpha 2-receptor agonist was independent of other hormone activity in the renal proximal tubule.

Effects of treatment on the histopathology of leprosy.

AIMS: To identify the histological changes in leprosy skin lesions over the first few weeks after the start of leprosy treatment and to examine their relationship to reversal reaction. METHODS: Sequential skin biopsy during treatment with multiple drug therapy. In this study, a series of 28 patients was studied, from whom two or more biopsies were taken at two week intervals. Fourteen patients had paucibacillary leprosy (PBL) and 14 had multibacillary leprosy (MBL). RESULTS: In most cases, granuloma fraction and bacterial index fell during treatment, the bacterial index being less sensitive than the granuloma fraction. Since the biopsies were fixed in buffered formalin and processed through to paraffin wax, little immunohistochemistry was feasible. However, there was strong evidence of immune activation, with increased expression of HLA-DR in the granulomas of MBL and PBL cases: the epidermis also expressed HLA-DR in several patients. Such changes may reflect gamma IFN production from granuloma lymphocytes. Patients with reversal reaction often showed HLA-DR expression on admission which decreased with corticosteroid treatment. CONCLUSIONS: The results suggest that activation of cell mediated immunity in leprosy lesions occurs during treatment with multiple drug therapy and may not be restricted to those with clinical evidence of reversal reaction.

Delayed hypersensitivity and HLA in smear-positive pulmonary tuberculosis.

Tuberculin responses were quantified by induration of the skin, velocity of blood flow in dermal microcirculation and composition of the cellular infiltrate in 125 patients with tuberculosis and 39 healty controls. The diameters of the tuberculin responses were greater in HLA-DR15-positive patients than in DR15-negative patients. The density of infiltrating CD(4+)-positive cells showed a positive correlation with induration in DR15-negative subjects (r = 0.54). A fraction of DR15-positive patients gave large tuberculin responses (> or = 15 mm) but with few CD4+ cells in the test site (< 500/mm2); these patients had a greater percentage of cells in the diffuse dermal infiltrate than in the perivascular region, greater blood flow velocities in the tuberculin response but more frequently with central relative slowing of blood flow and had higher total IgG and specific antimycobacterial antibody levels compared to other DR15-positive patients. If the inflammatory infiltrate in the lungs parallels that in the tuberculin skin test, the lack of immunocompetent cells and tissue hypoxia could permit pulmonary cavitation and explain the association of HLA-DR15 with smear-positive pulmonary tuberculosis.

Dibutyryl cyclic adenosine monophosphate stimulates the sodium pump in rabbit renal cortical tubules.

The elevation in oxygen consumption (QO2) observed following addition of the sodium ionophore nystatin in suspensions of rabbit renal proximal tubules was significantly increased by 1 mM dibutyryl cyclic adenosine monophosphate (db-cAMP). The QO2 after subsequent addition of strophanthidin to block the sodium pump was unaffected by db-cAMP. However, 10 microM forskolin in the presence of 100 microM IBMX had no significant effect on the QO2 observed following addition of either nystatin or strophanthidin. Nevertheless, we can conclude that db-cAMP does stimulate the sodium pump activity independently of sodium transport mechanisms in the rabbit renal proximal tubule.

Circulation and sensation at the fingertips of claw hands.

Measurements of skin blood flow (by laser Doppler flowmetry) and temperature were made under environmental conditions promoting peripheral vasodilatation at the fingertips of a disfigured 'clawed' hand in 12 leprosy patients long-resident at Baba Baghi Leprosy Hospital, Tabriz, Iran. Sensory function was assessed by measuring the responses to light touch, pain and temperature of each finger, and peripheral autonomic function was gauged by estimating palmer sweating and by measuring skin vasomotor reflexes in response to inspiratory gasp. In 2 patients all measured fingers had laser Dopper flux (LDFlux) values and skin temperatures lower than the 95% confidence limits for the mean of 20 healthy controls, i.e. were impaired; in 2 patients all fingers had normal values for LDFlux and temperature; and in 8 patients there was a combination of impairment with most fingers normal for these parameters but with the small finger most commonly impaired. There were 10 (67%) fingers with impaired LDFlux and temperature values who had significant sensory impairment, whereas only 5 (18%) of the fingers with normal LDFlux values and temperatures had a similar sensory deficit. Overall, the fingers with the most impaired sensation had significantly (P < 0.05) lower LDFlux and temperature values than those with no sensory deficit. Microcirculatory impairment was not related to disordered skin vasometer reflexes or dysfunction of sweating. We concluded that the relationship between motor (skeletal muscle) nerve paralysis and any subsequent sensory neuropathy and/or microcirculatory impairment is more complex than might be expected from previous understanding of the disease.

Different modulation of hepatocellular Na+/H+ exchange activity by insulin and EGF.

Indirect evidence suggests that insulin, like epidermal growth factor (EGF), stimulates liver cell Na+/H+ exchange. We directly studied the effect of insulin on intracellular pH (pHi) and the Na+/H+ exchanger in isolated rat hepatocytes with the fluorescent probe, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). The effects of insulin were compared with those of EGF. Studies were carried out in the absence of HCO3- and in the presence of acetazolamide to isolate the Na+/H+ exchanger from other pH regulatory mechanisms. Insulin (9 nM) caused a reversible acidification of baseline pHi, whereas no significant effect was observed with EGF (30 nM). pHi was acidified by two different methods (NH4Cl pulse and external Na+ removal) to assess liver cell Na+/H+ exchange activity. In the NH4Cl pulse experiments, insulin had no significant effect on the Na+/H+ exchanger compared with the control (0.141 +/- 0.009 pH units/min, n = 14, and 0.122 +/- 0.023 pH units/min, n = 16, respectively). However, in the same conditions, EGF nearly doubled the rate of the Na+/H+ exchange activity (0.193 +/- 0.015 pH units/min, P < 0.05, n = 6). In the Na+ removal experiments, EGF again significantly increased the pHi recovery rate (0.542 +/- 0.032 pH units/min, n = 3) compared with the control (0.227 +/- 0.028 pH units/min, n = 5) and insulin (0.245 +/- 0.053 pH units/min, n = 5). Compared with control conditions, a subchronic administration of insulin (9 nM) in vitro had no significant effect on the Na+/H+ exchanger, nor did it affect baseline pHi.(ABSTRACT TRUNCATED AT 250 WORDS)

Ca(2+)-activated K+ channels are involved in regulatory volume decrease in acinar cells isolated from the rat lacrimal gland.

The volumes of acinar cells isolated from rat lacrimal gland were measured on computer by video-imaging. Cells were found to swell on exposure to hypotonic solutions; they subsequently exhibited a regulatory volume decrease (RVD). RVD was inhibited in the absence of extracellular Ca2+, and by the K+ channel blocker tetraethylammonium chloride (2 mM TEA+). The possible involvement of K+ channels in RVD was further investigated in cell-attached patches. Exposing the cells to a hypotonic solution activated channels with a conductance of 141 +/- 6 pS (n = 11). These channels were partially blocked by 0.5 mM TEA+, and channel activation was not observed in the absence of extracellular Ca2+. Experiments in the inside-out patch configuration demonstrated that the channels activated by hypotonic stress were "maxi" Ca(2+)-activated K+ channels. It is concluded that the opening of these channels plays an important role in RVD, by facilitating K+ loss from the cell.

Effect of hyperoxia at 1 and 2 ATA on hypoxia and hypercapnia in human skin during experimental inflammation.

Transcutaneous PO2 and PCO2 measurements and estimates of skin respiration were monitored at different levels of inspired PO2 in 20 healthy adults during the first 4 days of the tuberculin reaction, a convenient model of acute inflammation. Hyperoxia at 1 and 2 ATA significantly increased transcutaneous PO2 levels in undisturbed and in inflamed skin but did not fully correct the relative hypoxia at the site of inflammation. Hypercapnia was reduced with O2 breathing at 2 ATA. The apparent rate of O2 consumption at the reaction site was raised during hyperoxia, most prominently at 2 ATA. The most intense reactions showed a central relative slowing of laser-Doppler blood flow indicative of microcirculatory impairment. The extent of the relative hypoxia and hypercapnia was greatest in these strongest reactions. The density of lymphocytes and monocytes in biopsies of 48-h reactions was loosely related to the corresponding transcutaneous PO2 measurements. The present study provides evidence that diffusion barriers, in addition to increased local respiration, can contribute to the apparent hypoxia and hypercapnia of this inflammatory model.