Recommendations for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia.

There have recently been safety concerns regarding an increased risk of vaccine-induced immune thrombotic thrombocytopenia (VITT) following administration of SARS-CoV-2 adenoviral vector vaccines. The Southern African Society of Thrombosis and Haemostasis reviewed the emerging literature on this idiosyncratic complication. A draft document was produced and revised by consensus agreement by a panel of professionals from various specialties. The recommendations were adjudicated by independent international experts to avoid local bias. We present concise, practical guidelines for the clinical management of VITT.

Treatment of pulmonary arterial hypertension: A review of drugs available for advanced therapy.

Pulmonary hypertension (PH) has traditionally been considered a rare disease with a uniformly poor prognosis. However, this was prior to the introduction of advanced therapies for this condition, and more recent registries in the treatment era have shown 5-year survival rates of up to 65%. Prior to 2000, there was only one licensed therapy for pulmonary arterial hypertension (PAH); less than 20 years later, the US Food and Drug Administration has approved 14 different medications for PAH. This review aims to summarise for the general pulmonologist the evidence for the current internationally available advanced therapies for PAH (World Health Organization Group I disease), which is characterised haemodynamically by the presence of precapillary PH in the absence of another cause. The benefit of these agents, either alone or in combinations, is now undisputed and their use is advocated in all current international guidelines for PAH. The improvement in survival of patients with PAH over the concurrent timeline emphasises the importance both of the availability and usage of effective therapies and of patients being seen in specialist centres, where physicians are familiar with using these therapies.

Management of pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a potentially lethal disease mainly affecting young females. Although the precise mechanism of PAH is unknown, the past decade has seen the advent of many new classes of drugs with improvement in the overall prognosis of the disease. Unfortunately the therapeutic options for PAH in South Africa are severely limited. The Working Group on PAH is a joint effort by the South African Heart Association and the South African Thoracic Society tasked with improving the recognition and management of patients with PAH. This article provides a brief summary of the disease and the recommendations of the first meeting of the Working Group.

20p11 deletion in a female child with panhypopituitarism, cleft lip and palate, dysmorphic facial features, global developmental delay and seizure disorder.

Deletions of 20p are rare with the majority of reported cases involving individuals with 20p12 deletions associated with Alagille syndrome. We report on a child with a de novo mosaic 20p11 deletion who presents with panhypopituitarism; hypoplastic pituitary gland and ectopic posterior pituitary gland on MRI of the brain; cleft lip and palate; kyphosis with anterior beaking of L1 and L2 vertebral bodies; pulmonic stenosis; dysmorphic facial features including flat nasal bridge, hypoplastic premaxilla, hypotelorism, preauricular pit, and cupped ears; seizure disorder; variable muscle tone; and global developmental delay. Array comparative genomic hybridization revealed this deletion to be approximately 5.4 Mb in size, containing 35 genes. Previously, an infant with 20p11.22 deletion who had panhypopituitarism, craniofacial, and genital abnormalities was reported, but the precise parameters of that deletion are unavailable. Several other reported cases of 20p11 deletions also have phenotypic overlap with our case. The similarities in clinical features of these patients suggest that the genes at 20p11 have a critical role in development of midline brain structures.

Personality correlates of glycemic control in type 2 diabetes.

OBJECTIVE: To determine whether traits of normal personality are associated with variations in glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A longitudinal cohort study was conducted using data from 105 type 2 diabetic patients in a clinical trial of a stress management intervention. Before treatment assignment, patients completed the NEO Personality Inventory, Revised, which is a questionnaire inventory measuring 5 major domains of normal personality and 30 important traits that define these domains. Glycemic control was assessed by measures of HbA1c and average blood glucose levels based on 7 days of self-monitoring at baseline and at 6 and 12 months. Relationships between personality traits and measures of glycemic control were examined by correlation and linear regression models that were adjusted for age, sex, race, duration of diabetes, medication status, and experimental treatment. RESULTS: Lower average blood glucose values at baseline were associated with higher scores for the personality domain of neuroticism and several specific traits including anxiety, angry hostility depression, self-consciousness, and vulnerability but were associated with lower scores for the trait of altruism. Results were similar for HbA1c but were not as strong. Follow-up results were similar but were less consistent. CONCLUSIONS: Personality traits may offer new insights into variations in glycemic control in patients with type 2 diabetes undergoing standard management. The relative tendency to experience fewer negative emotions and to focus on the needs of others instead of oneself could prove to be a risk factor for poor glycemic control.

Recent developments in tritium incorporation for radiotracer studies.

The essential nature of rapid radiotracer synthesis very early in drug discovery programs has driven the need for better and more varied tritium incorporation methods. This review presents a summary of recent advances for tritium introduction via tritiated water, tritium gas, complex tritides, and a range of recently improved tritiation reagents. Access to a wider range of tritiated reagents (for tritioacetylation, tritioformylation, methylation, etc.) and commercial manifolds for the transfer and use of tritium gas is also discussed.

Inhibition of protein synthesis by didemnin B: how EF-1alpha mediates inhibition of translocation.

The antineoplastic cyclic depsipeptide didemnin B (DB) inhibits protein synthesis in cells and in vitro. The stage at which DB inhibits protein synthesis in cells is not known, although dehydrodidemnin B arrests translation at the stage of polypeptide elongation. Inhibition of protein synthesis by DB in vitro also occurs at the elongation stage, and it was shown previously that DB prevents EF-2-dependent translocation in partial reaction models of protein synthesis. This inhibition of translocation displays an absolute requirement for EF-1alpha; however, the dependence upon EF-1alpha was previously unexplained. It is shown here that DB binds only weakly to EF-1alpha/GTP in solution, but binds to ribosome. EF-1alpha complexes with a dissociation constant K(d) = 4 microM. Thus, the inhibition of protein synthesis by DB appears to involve an interaction with both EF-1alpha and ribosomes in which all three components are required. Using diphtheria toxin-mediated ADP-ribosylation to assay for EF-2, it is demonstrated that DB blocks EF-2 binding to pre-translocative ribosome.EF-1alpha complexes, thus preventing ribosomal translocation. Based on this model for protein synthesis inhibition by DB, and the proposed mechanism of action of fusidic acid, evidence is presented in support of the Grasmuk model for EF-1alpha function in which this elongation factor does not fully depart the ribosome during polypeptide elongation.

Examining communication and assertiveness as predictors of condom use: implications for HIV prevention.

The current study explored the relationship between communication and assertiveness in general and sexual contexts and examined each construct's differential ability to predict reported condom use among college students. The results suggest that the constructs are positively related to each other, but general communication does not predict sexual assertiveness. Although sexual assertiveness is a better predictor of condom use than general assertiveness, general communication, and sexual communication, it needs to be considered within the context of other variables (e.g., normative beliefs regarding condom use). HIV prevention programs and models of health behavior should incorporate individual characteristics such as sexual assertiveness. The results of this study suggest that sexual assertiveness, social norm perceptions of condom use, self-efficacy for HIV prevention, and condom attitudes are among the critical variables that should be examined in an integrated model of sexual health behavior.

Eating habits of children with autism.

Autism is a developmental disorder characterized by severe deficits in social interaction and communication, as well as by stereotyped and repetitive behaviors. Children with autism frequently have significant eating difficulties with highly restricted range of food choices. Eating habits and patterns are often unusual and have an impact on family life. The purpose of this article was to review pertinent information regarding this complex developmental disorder and describe a recent study based on a parent survey of feeding patterns in children with autism to give a new perspective for both parents and professionals.

[3H]Azidodantrolene: synthesis and use in identification of a putative skeletal muscle dantrolene binding site in sarcoplasmic reticulum.

Dantrolene sodium is a medically important hydantoin derivative that interferes with release of Ca2+ from intracellular stores of skeletal muscle by an unknown mechanism. Identification of the molecular target of dantrolene would greatly aid in understanding both the mechanism of action of the drug and the dynamics of intracellular Ca2+ release in muscle. [3H]Azidodantrolene was designed and synthesized as a photoaffinity analogue in order to identify a putative dantrolene receptor in skeletal muscle. Introduction of 1 mole-atom of tritium into aldehyde 5b was required during radioligand synthesis in order to ensure high enough specific activity for detection of photo-cross-linked proteins by fluorographic methods. This was accomplished by reduction of ester 3 with custom synthesized, 100% tritium-labeled lithium triethylborotritide, followed by oxidation to 5b by manganese(IV) oxide. Compound 6b was demonstrated to be >/=95% tritium-labeled at the imine position by NMR spectroscopy, and the specific radioactivity of [3H]azidodantrolene sodium was empirically determined by HPLC and liquid scintillation counting to be 24.4 Ci/mmol, approximately 85% of theoretical maximum. [3H]Azidodantrolene was found to be pharmacologically active in ligand-receptor binding studies with skeletal muscle sarcoplasmic reticulum membranes. Photo-cross-linking experiments analyzed by SDS-PAGE and tritium fluorography have identified a approximately 160-kDa specifically labeled protein as the putative, intracellular, skeletal muscle dantrolene receptor. This photolabeled protein comigrates with a protein in Western blots immunologically cross-reactive to a polyclonal anti-rabbit skeletal muscle ryanodine receptor antibody. Thus, the putative dantrolene receptor may be related to the skeletal muscle ryanodine receptor.

Case reports in autism: issues in diagnosis and treatment.

Autism is a relatively common developmental disorder characterized by pervasive impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Two case reports are presented to illustrate important aspects of diagnosis and treatment. Early clinical diagnosis is essential so that appropriate intervention can be implemented. A multidisciplinary approach to treatment is recommended due to the impact of autism on many aspects of behavior and development.

Personality predictors of mood related to dieting.

The clinical utility of a model of normal emotional functioning (vs. psychopathology) and the moderating effects of neuroticism (N) and extraversion (E) on mood were examined during a 6-week weight-loss trial. Participants were 40 obese women who completed measures of negative affect (NA) and positive affect (PA) weekly during the diet and measures of anxiety and depression (Beck Depression Inventory [BDI]) at pre-, mid-, and postdiet. Results indicated that (a) average NA and PA were each uniquely related to postdiet BDI scores, (b) N was significantly related to NA during the diet and postdiet BDI scores, and (c) N and E interacted to predict PA during the diet. The results suggest that assessment of personality and normal mood variation may be useful additions to weight-loss intervention and research.

Social marketing to eliminate leprosy in Sri Lanka.

PIP: Leprosy is a chronic infectious disease which, if untreated, can lead to permanent and progressive nerve damage and thus to deformities of the limbs, eyes, and face. People with leprosy have long been ostracized by society. The clinical signs of leprosy include insensitive skin lesions and thickened peripheral nerves. Untreated infectious leprosy cases are the main source of infection, transmitting the disease through nasal secretions. People with low cell-mediated immunity are at risk of developing clinically active leprosy irrespective of gender, age, or social class. The World Health Organization (WHO) has, since 1982, recommended multiple drug therapy (MDT) against leprosy, an approach capable of curing the disease within 1 year and interrupting its transmission. According to WHO, leprosy is currently a public health problem in 55 countries and more than 20% of the estimated 1.15 million cases of leprosy worldwide remain undetected. Although Sri Lanka was the first country in South Asia to provide MDT to all registered leprosy patients, first making it available in 1984, the disease continues to be transmitted due to the large number of undetected cases in the country. An ongoing social marketing program was therefore launched in 1990 by the local health ministry and the Novartis Foundation for Sustainable Development to eliminate leprosy from Sri Lanka. The program encourages people with suspicious skin lesions to seek diagnosis and care, teaches health care providers to recognize leprosy and refer cases for treatment, and helps the general public to understand that leprosy is just a normal disease. The socially marketed product is MDT, provided free-of-charge by the Novartis Foundation to all leprosy patients.^ieng

Tritium NMR studies of the human carbonic anhydrase I-benzenesulfonamide complex.

Tritium NMR spectroscopy has been used to examine the complex formed by [4-3H]benzenesulfon-amide and human carbonic anhydrase I. The results show that in solution the inhibitor forms a 1:1 complex with the enzyme. A 100-spin computational model of the system, constructed with reference to crystallographic results, was used to interpret tritium relaxation behavior and 3H{1H} NOEs. The analysis shows that the rate of dissociation of the enzyme-sulfonamide complex is 0.35 s-1 and that the aromatic ring of the inhibitor undergoes rapid rotation while complexed.

A male with fetal valproate syndrome and autism.

Fetal valproate syndrome (FVS) is characterized by minor craniofacial anomalies, major organ malformations, and developmental delay. We report on a patient who has a clinical phenotype compatible with both FVS and autism. The presence of an autistic disorder in a previously reported case of FVS and similar findings in our patient suggest that a relation between this known teratogen and autism may exist.