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The role of thromboelastography in the management of children with snake-bite in southern Africa.

In the absence of a direct laboratory test of envenomation, there is a need for an alternative mechanism for the early recognition of envenomation following snake-bite in children. A severe clinical diathesis may result either from envenomation or from the release of an inappropriate tourniquet applied as 'first-aid' often several hours before presentation to hospital. Abnormalities of clotting are associated with both events. A normal thromboelastogram (TEG) provides early recognition of patients in whom the clinical course is likely to be benign (sensitivity = 94%). An abnormal TEG identifies patients of whom 50% will develop a severe clinical diathesis. A TEG is a more accurate predictor of disease severity than International Normalized Ratio alone. The TEG does not supplant clinical observation in the management of snake-bite in children but allows stratification into high- and low-risk categories.

Child↗

Lonomia achelous caterpillar venom (LACV) selectively inactivates blood clotting factor XIII.

Lonomia Achelous Caterpillar Venom (LACV) causes a severe acquired bleeding diathesis in exposed persons. The condition is characterized by prolonged bleeding from superficial wounds and mucous membranes. Intracranial or intra-abdominal hemorrhage is a common and often fatal complication. A constant finding in these cases is a profound decrease of clotting Factor XIII (FXIII) activity. In the present study, the effects of LACV on plasmatic and purified human FXIII has been evaluated. The results show that native LACV and one of its chromatographically purified fractions (termed FIID) produce a dose dependent decrease of FXIII activity accompanied with an impairment of fibrin(ogen) crosslinking. We conclude that the inactivation of FXIII by fraction FIID (which will be named Lonomin V), is one of the principal patho-physiological mechanisms behind the acquired bleeding diathesis seen in these cases.

Animals↗

Molecular genetic approaches to puerperal psychosis.

Puerperal psychosis, an episode of mania or psychosis precipitated by childbirth follows approximately one in 1000 deliveries. The evidence of clinical, outcome and genetic studies supports the hypothesis that the majority of puerperal psychotic episodes are manifestations of an affective disorder diathesis with a puerperal trigger. Furthermore the available evidence supports the hypothesis that genes are involved in susceptibility to both diathesis and trigger. For complex genetic disorders such as affective illness there are marked benefits in focussing on a homogeneous subtype which allows a subset of hypotheses to be tested. Molecular genetic studies of puerperal psychosis provide an excellent example of this strategy, allowing a hierarchy of hypotheses concerning the involvement of neurosteroid pathways in pathophysiology to be tested. Puerperal psychosis results in considerable suffering to a woman and her family. Elucidating the pathophysiological basis of this disorder will lead to better prevention and treatment and, it is anticipated, inform research on affective disorders more generally.

Bipolar Disorder↗

Allergic sensitization increases airway reactivity in guinea pigs with respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) causes acute bronchiolitis in children and has been implicated in the pathogenesis of recurrent wheezing and asthma. However, few children exposed to RSV experience acute bronchiolitis or its sequelae, suggesting a subgroup of susceptible children. An allergic diathesis may predispose children to subsequent airway disease. OBJECTIVE: This study was carried out to determine whether a preexisting allergic state, induced by repeated inhalational exposures to ovalbumin, potentiates nonspecific airway responsiveness to acetylcholine and increases airway inflammation during acute RSV bronchiolitis in guinea pigs. METHODS: Forty guinea pigs were randomized into four groups: nonsensitized, noninfected (ovalbumin-, RSV-); sensitized, noninfected (ovalbumin+, RSV-); nonsensitized, infected (ovalbumin-, RSV+); sensitized, infected (ovalbumin+, RSV+). Depending on grouping, animals were exposed to either repeated aerosols of ovalbumin or saline solution and were subsequently inoculated with either human RSV or uninfected culture medium. Six days after inoculation, animals underwent acetylcholine challenge, and lung specimens were prepared for histologic scoring of airway inflammation. RESULTS: Maximal increases in pulmonary resistance (centimeters of water per milliliter per second) to acetylcholine were greater for RSV alone (12.4 +/- 3.9) and ovalbumin alone (13.7 +/- 3.9) compared with controls (4.3 +/- 1.1), but significantly greater increases occurred in ovalbumin+, RSV+ animals (34.0 +/- 11.0). These ovalbumin+, RSV+ animals demonstrated the combined histologic changes noted with RSV alone and ovalbumin alone including airway epithelial necrosis, mononuclear and granulocyte infiltrates, airway wall edema, hyperplasia of bronchus-associated lymphoid tissue, and goblet cell metaplasia. CONCLUSION: Prior allergic sensitization potentiates the physiologic and structural changes induced by acute RSV bronchiolitis. These results suggest that an allergic diathesis may increase the severity of RSV infections in children.

Acetylcholine↗

The clinical spectrum of atopic dermatitis.

Updating our clinical concept of atopic dermatitis (AD) evolves from the better understanding of all the immunologic aberrations expressed by the polygenic combinations and permutations associated with the atopic diathesis. Recognizing the immunopathologic features of AD readily underscores that AD without "atopy" is an oxymoron. Appreciating "pruritus" as the impetus to scratch, which isomorphically gives rise to the "eczema," shifts the goal of management from suppressing inflammation to avoiding the triggers of pruritus. Recognizing the full spectrum of dermatologic findings in AD endorses the preferred label as a dermatitis, rather than the inferred restrictive label, atopic eczema. As our knowledge of immunology evolves, our criteria for the diagnosis and management of the atopic diathesis are sure to change.

Adult↗

Passovoy factor: A hitherto unrecognised factor necessary for haemostasis.

A moderate bleeding diathesis transmitted as an autosomal dominant was found in five members of four generations of the same family. The affected patients had prolonged partial thromboplastin-times and normal levels of all the known clotting-factors. The haemorrhagic diathesis was attributed to a deficiency of a hitherto unrecognised coagulation factor--i.e., the Passovoy facto.

Adult↗

The role of cyclothymia in atypical depression: toward a data-based reconceptualization of the borderline-bipolar II connection.

OBJECTIVE: Recent data, including our own, indicate significant overlap between atypical depression and bipolar II. Furthermore, the affective fluctuations of patients with these disorders are difficult to separate, on clinical grounds, from cyclothymic temperamental and borderline personality disorders. The present analyses are part of an ongoing Pisa-San Diego investigation to examine whether interpersonal sensitivity, mood reactivity and cyclothymic mood swings constitute a common diathesis underlying the atypical depression-bipolar II-borderline personality constructs. METHOD: We examined in a semi-structured format 107 consecutive patients who met criteria for major depressive episode with DSM-IV atypical features. Patients were further evaluated on the basis of the Atypical Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL-90), and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified form for reverse vegetative features as well as Axis I and SCID-II evaluated Axis II comorbidity, and cyclothymic dispositions ('APA Review', American Psychiatric Press, Washington DC, 1992). RESULTS: Seventy-eight percent of atypical depressives met criteria for bipolar spectrum-principally bipolar II-disorder. Forty-five patients who met the criteria for cyclothymic temperament, compared with the 62 who did not, were indistinguishable on demographic, familial and clinical features, but were significantly higher in lifetime comorbidity for panic disorder with agoraphobia, alcohol abuse, bulimia nervosa, as well as borderline and dependent personality disorders. Cyclothymic atypical depressives also scored higher on the ADDS items of maximum reactivity of mood, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the interpersonal sensitivity, phobic anxiety, paranoid ideation and psychoticism of the HSCL-90 factors. The total number of cyclothymic traits was significantly correlated with 'maximum' reactivity of mood and interpersonal sensitivity. A significant correlation was also found between interpersonal sensitivity and 'usual' and 'maximum' reactivity of mood. LIMITATION: Correlational study. CONCLUSIONS: Mood lability and interpersonal sensitivity traits appear to be related by a cyclothymic temperamental diathesis which, in turn, appears to underlie the complex pattern of anxiety, mood and impulsive disorders which atypical depressive, bipolar II and borderline patients display clinically. We submit that conceptualizing these constructs as being related will make patients in this realm more accessible to pharmacological and psychological interventions geared to their common temperamental attributes. More generally, we submit that the construct of borderline personality disorder is better covered by more conventional diagnostic entities.

Adolescent↗

Alcoholism and drug abuse in three groups--bipolar I, unipolars and their acquaintances.

OBJECTIVE: Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. METHOD: Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls = 469; bipolars = 277; unipolar depressives = 678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. RESULTS: The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. LIMITATION: As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. CONCLUSIONS: (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. CLINICAL IMPLICATIONS: The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials.

Adult↗

Substance use disorders, externalizing psychopathology, and P300 event-related potential amplitude.

We hypothesize the existence of an inherited predisposition for a spectrum of behaviors and traits characterized by behavioral disinhibition. This externalizing spectrum includes childhood disruptive disorders, antisocial behavior, substance use disorders, personality traits related to behavioral undercontrol, and the precocious expression of problem behavior. We further hypothesize that a genetically influenced central nervous system diathesis underlies this spectrum and is reflected in reduced P300 amplitude in a visual oddball event-related potential task. A review of evidence bearing on the model is derived from findings from the Minnesota Twin Family Study, a population-based, longitudinal investigation of twin youth. These findings indicate that the collection of attributes related to behavioral disinhibition is familial, heritable, and interrelated. Evidence supporting P3 amplitude reduction (P3-AR) as an index of genetic vulnerability for this externalizing spectrum includes its association with (a) familial risk for substance use and antisocial personality disorders, (b) diagnoses of childhood disruptive disorders and substance use disorders, (c) early onset of undersocialized behavior, and (d) quantitative phenotypes related to externalizing problems. In addition, the development of substance use disorders over a 3-year period is associated with P3-AR measured prior to their expression. These findings suggest that P3-AR indexes one aspect of the genetic diathesis for a spectrum of externalizing problem behavior.

Adolescent↗

Air pollution and its effect on the upper respiratory tract and on allergic rhinosinusitis.

The nose is the first organ system encountered by inhaled air and its associated pollutants. Pollutants are deposited during inspiration through the nose. They accumulate on mucus and are absorbed in the nasal mucosa, resulting in a number of deleterious effects on the body. Irritation of the nose and sinus from these pollutants, resulting from direct contact with the nasal mucosa, leads to inflammation, edema, swelling, and blocked sinuses. The result is acute and chronic sinusitis. Absorption of these chemicals into the body produces systemic effects. Their effect on the immune system, although subtle, leads to dramatic changes in the allergic diathesis. The T suppressor cell is the most sensitive cell of the immune system and the first to be affected by exposure to chemical pollutants. Diminution of the suppressor activity and the relative increase in helper activity in turn lead to increased immunoglobulin production and the manifestation of allergy symptoms. The underlying biochemical reaction is caused by the effects of pollutants on the T suppressor cell. Patients with existing allergies become brittle and difficult to treat with the exacerbation of the allergic diathesis. Removal of these chemical pollutants from the body as quickly as possible is essential for effective treatment of this problem. Dietary antioxidants help reduce the oxidizing effect of the pollutants and act as conjugators to remove the pollutants from the body.

Absorption↗

Spinal subdural hematoma.

Although spinal subdural hematoma is a rare condition, it has a higher incidence in persons with a bleeding diathesis and in those with a bleeding diathesis who have had a lumbar puncture. We report a case of a 65-year-old woman on oral anticoagulants presenting with atypical symptoms who developed a spinal subdural hematoma over a six-hour period. This resulted in complete paraplegia of her lower extremities with no improvement after surgical spinal cord decompression.

Female↗

Genetic and environmental risk factors for the onset of drug use and problems in adoptees.

Applying survival analysis methodology to age-of-onset data from an adoption study (N = 196), we present evidence that risks for both drug use and drug problems (DSM abuse or dependence) are elevated when combined antisocial personality (ASP) and substance abuse is present in the same biological parent. It is increased not only in comparison to adoptees with no known biological risk, but also when compared to adoptees with a biological background for only substance problems or only ASP. Neither of these later groups showed a statistically higher risk when compared with controls. Among adoptees with recurrent drug use, adolescent aggressivity is also elevated when the combined substance abuse/ASP biological diathesis is present. Statistical control for aggressivity diminished but did not eliminate the predictive significance of the combined biological diathesis for drug problems. We also verify, using more refined methodology, our previous reports of gender and adverse adoptive environmental influences on drug-related outcomes in these subjects. We could not document a biology-environment interaction, but power to do so was rather low. We argue that the observed biological associations are broadly consistent with generalization to other substances of an alcoholism phenotype similar to Cloninger's Type II or Babor's Type B.

Adolescent↗

Inherited bleeding disorders.

Congenital bleeding disorders comprise a heterogeneous group of diseases that reflect abnormalities of blood vessels, coagulation proteins and platelets. Studies of these diseases, many of which are rare and several of which result in a mild bleeding diathesis only, have significantly increased our understanding of normal haemostasis. Two lessons have been learned. First, quantitative abnormalities of coagulation proteins and platelets are an important, but not the only, cause of significant haemorrhage; some cases of inherited bleeding disorders reflect synthesis of a dysfunctional coagulation protein or production of abnormal platelets. Diagnostic tests that reflect qualitative abnormalities are therefore important in the evaluation of selected patients with inherited bleeding disorders. Second, in occasional patients the inherited disorder is complex and reflects combined abnormalities of coagulation proteins alone or in association with platelet disorders. In clinical practice it is useful to distinguish disorders that cause significant clinical bleeding from those that cause few or no symptoms. Examples of the former include severe deficiencies of factors VIII and IX, and the homozygous forms of factor II, V, VII, X, XI, XIII, fibrinogen and von Willebrand factor. Comparable platelet disorders include the inherited thrombocytopenias with platelet counts less than 20 x 10(9) litre-1 and the homozygous forms of Bernard-Soulier syndrome and Glanzmann's thrombasthenia. The most frequently encountered mild haemostatic abnormalities include type I von Willebrand's disease, the platelet storage pool deficiency syndromes and the mild and moderate forms of haemophilia A and B; occasionally heterozygous or homozygous forms of the rarer coagulation disorders, e.g. factor XI deficiency, may present with a mild bleeding diathesis. Finally, some disorders are entirely asymptomatic, e.g. factor XII deficiency and deficiencies of other contact coagulation factors. Management of patients with inherited bleeding disorders should reflect knowledge of the specific disorder to be treated plus careful consideration of the clinical circumstance for which therapy is proposed. In all cases, once a decision to treat has been made, the safest efficacious therapy should be given (for example DDAVP in the treatment of patients with mild haemophilia A or type I von Willebrand's disease). Although blood products are now much safer and the risk of blood transmitted viral infections is low, there still remains a risk that transfusion of any blood product may be associated with serious side-effects. As a result, therapy should be given only after careful consideration of the risk: benefit ratio and not merely to treat an abnormal laboratory result.(ABSTRACT TRUNCATED AT 400 WORDS)

Afibrinogenemia↗

Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye.

Vasospasm can have many different causes and can occur in a variety of diseases, including infectious, autoimmune, and ophthalmic diseases, as well as in otherwise healthy subjects. We distinguish between the primary vasospastic syndrome and secondary vasospasm. The term "vasospastic syndrome" summarizes the symptoms of patients having such a diathesis as responding with spasm to stimuli like cold or emotional stress. Secondary vasospasm can occur in a number of autoimmune diseases, such as multiple sclerosis, lupus erythematosus, antiphospholipid syndrome, rheumatoid polyarthritis, giant cell arteritis, Behcet's disease, Buerger's disease and preeclampsia, and also in infectious diseases such as AIDS. Other potential causes for vasospasm are hemorrhages, homocysteinemia, head injury, acute intermittent porphyria, sickle cell disease, anorexia nervosa, Susac syndrome, mitochondriopathies, tumors, colitis ulcerosa, Crohn's disease, arteriosclerosis and drugs. Patients with primary vasospastic syndrome tend to suffer from cold hands, low blood pressure, and even migraine and silent myocardial ischemia. Valuable diagnostic tools for vasospastic diathesis are nailfold capillary microscopy and angiography, but probably the best indicator is an increased plasma level of endothelin-1. The eye is frequently involved in the vasospastic syndrome, and ocular manifestations of vasospasm include alteration of conjunctival vessels, corneal edema, retinal arterial and venous occlusions, choroidal ischemia, amaurosis fugax, AION, and glaucoma. Since the clinical impact of vascular dysregulation has only really been appreciated in the last few years, there has been little research in the according therapeutic field. The role of calcium channel blockers, magnesium, endothelin and glutamate antagonists, and gene therapy are discussed.

Constriction, Pathologic↗

Chronic spinal disorders and psychopathology. research findings and theoretical considerations.

BACKGROUND CONTEXT: Numerous studies have documented a strong association between chronic spinal disorders and psychopathology. However, there have been methodological shortcomings associated with much of this. PURPOSE: This article reviews the relevant research literature, including methodological refinements that have resulted in improved measurement of psychopathology, in order to provide the most updated conclusions concerning the links between spinal disorders and psychopathology. STUDY DESIGN: A systematic review of all Medline referenced articles on this subject during the past three decades. METHODS: Previous research has shown that chronic spinal disorders are most often associated with depressive disorders, somatoform disorders, anxiety disorders, substance use disorders, and personality disorders. In addition to reviewing this research, the relationship between chronic spinal disorders and depressive disorders is examined in more detail. RESULTS: Although the relationship between spinal disorders and psychopathology is complex, a diathesis-stress model is emerging as the dominant overarching theoretical model. In this model, diatheses are conceptualized as pre-existing semidormant characteristics of the individual before the onset of chronic spinal disorders, which are then activated by the stress of this chronic condition, eventually resulting in a diagnosable depressive disorder. CONCLUSIONS: In the present review, a diathesis-stress model was applied specifically to the relationship between chronic spinal disorders and depressive disorders. Such a model may also be applicable to the relationship between chronic spinal disorders and other types of psychopathology, such as anxiety and substance use disorders. However, conclusive empirical support will require a prospective research design, given that these diatheses could be validly assessed only before the onset of the chronic pain condition.

Chronic Disease↗

Attachment, autonomy, and multifinality in adolescent internalizing and risky behavioral symptoms.

A diathesis-stress interaction model is used to describe multifinality in adolescent internalizing and risky behavioral outcomes. Problematic behavior associated with adolescent insecure preoccupation (a diathesis) was expected to interact with the level of maternal autonomous discourse (a stressor) to predict specific adolescent outcomes. Assessments of adolescent preoccupied attachment organization, observations of maternal displays of autonomy in mother-adolescent interactions, and adolescent reports of internalizing symptoms and risky behaviors were obtained at age 16. As predicted, maternal autonomy in the mother-adolescent relationship helped to explain multifinality in dysfunctional symptoms among preoccupied adolescents. Adolescent preoccupation was more strongly linked to internalizing behavior when mothers demonstrated low levels of autonomy in interactions with their adolescents and more strongly linked to risky behavior when mothers displayed extremely high levels of autonomy. Implications for autonomy processes in increasing our understanding of how adolescent insecure-preoccupation relates to profiles of specific problems during adolescence are discussed as is the importance of exploring the role of attachment in different contexts.

Adolescent↗

Decreased platelet membrane anisotropy in patients with adrenoleukodystrophy treated with erucic acid (22:1)-rich triglycerides.

Low platelet count and bleeding diathesis have been observed in patients with adrenoleukodystrophy (ALD) treated with erucic acid (22:1)-rich triglycerides ("Lorenzo's oil'). To investigate possible alterations of biophysical membrane properties, we measured platelet membrane anisotropy, which is inversely related to membrane fluidity, in 16 patients with and in 3 patients without treatment. In patients on treatment, platelet membrane anisotropy was significantly decreased. Additionally, we found increased platelet concentrations of 22:1 and compromised in vitro platelet aggregation response. The decrease of platelet membrane anisotropy is probably a main cause of bleeding diathesis. Long-term haematological side-effects must be considered in ALD patients treated with Lorenzo's oil.

Adolescent↗

Depressive reactions to failure in a naturalistic setting: a test of the hopelessness and self-esteem theories of depression.

We tested the hopelessness and self-esteem theories of depression and an integration of the two by examining whether a stable, global attributional style (attributional diathesis) and low self-esteem interacted with the outcomes students received on a midterm examination to predict their subsequent depressive reactions over the course of 5 days. Students' immediate depressive reactions (on receipt of grades) were predicted solely by the examination outcome, whereas their enduring depressive reactions during the following 4 days were predicted by the Attributional Diathesis x Low Self-Esteem x Failure interaction. The results also indicated that the three-way interaction predicted enduring depressive reactions through the mediating role of hopelessness.

Adaptation, Psychological↗