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.

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.

Structure and dynamics of tosylchymotrypsin at pH 7 examined by tritium NMR spectroscopy.

3H-NMR spectroscopy of specifically tritiated and tritiated/deuterated derivatives of tosylchymotrypsin has been used to examine the behavior of the tosyl group in this protein at pH 7. The presence of several tritiated isotopomers complicates analysis of experiments and extensive computer simulations of T1 relaxation, line widths, and various nuclear Overhauser experiments for the collection of tritiated species present in the samples were used to the interpret the observations made. These analyses suggests that the tosyl group of tosylchymotrypsin at pH 7 is largely retained within the substrate specificity pocket observed in the crystal structure. This outcome is in strong contrast to the situation observed at pH 4, where the tosyl group is mobile enough to be found outside the specificity pocket an appreciable fraction of the time, and may be the result of protein association at pH 7.

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.

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.

Vinblastine sensitivity of leukaemic lymphoblasts modulated by serum lipid.

The high-resolution proton magnetic resonance spectrum of leukaemic lymphoblasts is characteristic of neutral lipid in an isotropic environment. When such lymphoblasts are selected for resistance to the anticancer drug vinblastine, the intensity of this spectrum increases with increasing drug resistance. A reversal of this trend can be achieved by growing cells in delipidated serum, whereby lipid spectrum and drug resistance are diminished. However, both can be restored by subsequent regrowth in normal medium. Thus, although detectable genetic changes accompany the development of vinblastine resistance, the expression of these changes can be modulated by environmental lipid.

Lipid domain in cancer cell plasma membrane shown by 1H NMR to be similar to a lipoprotein.

Human blood lipoproteins have been characterised by 1H NMR methods and chemical analysis, and comparisons made with the properties of the triglyceride-rich plasma membrane domain found in cancer cells. By means of selective and non-selective T1 experiments, the lipids in HDL and LDL are shown to be in diffusive exchange. In contrast, the lipids of chylomicra and VLDL do not exhibit lipid diffusion, and therefore resemble the neutral lipids of cancer cell plasma membranes. 2D scalar correlated NMR (COSY) spectra of cancer cells or solid tumours are similar to those obtained from VLDL and LDL. The long T2 relaxation value observed for neutral lipid methylenes in metastatic cancer cells (greater than 300 ms) was not observed for any of the 4 lipoproteins studied. None of the lipoprotein classes gave a T2 longer than 250 ms.

Cell surface involvement in cancer metastasis: an NMR study.

NMR spectroscopy is one of the few techniques which has the sensitivity to detect subtle changes to the surface chemistry of cells. It has previously been demonstrated that high resolution 1H NMR methods can distinguish tumour cells with the capacity to metastasis and this information appears to arise from a type of proteolipid in or attached to the plasma membrane. Here we report that the 1H NMR signal, which we have used to identify metastatic cells in rat tumours, is significantly reduced in intensity after cultured cells are treated with trypsin/EDTA. The long T2 relaxation value (greater than 350 ms) observed in metastatic cells is absent after enzyme treatment. 2D scalar correlated NMR (COSY) spectra of these treated cells show that a cross peak normally associated with malignancy and metastatic disease is markedly reduced. These findings indicate that the plasma membrane lipid particle which generates the high resolution spectrum is directly affected by trypsin/EDTA. Alterations to the cell surface properties were also demonstrated in vivo since reduced numbers of metastases were observed in animals injected with enzyme-treated cells. The correlation between the absence of a long T2 relaxation value and the diminished numbers of metastases in animals suggests that the plasma membrane particle is involved in the metastatic PROCESS.

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.

Use of nuclear magnetic resonance in probing ligand-macromolecule interactions.

Nuclear magnetic resonance techniques can be used to study ligand-macromolecule interactions under a wide variety of conditions. There are a number of different approaches, which are generally applicable under different conditions of exchange rate and binding constant. In the tight binding limit direct structural studies using NOE are possible using labeled ligand (13C, 15N) and/or labeled macromolecule. In the intermediate exchange regime, line broadening complicates the analysis of bound conformations of ligands. However, a good deal of information can be obtained about the binding kinetics and about the number and nature of binding modes when several are present. In such cases it is often best to use an NMR active nucleus which can be directly detected, with high sensitivity. Tritium has good characteristics in this respect, and has been effective in a number of cases. In the fast exchange limit it is often best to use the rapid dissociation of the ligand to transfer structural information from the bound form to the free, where it can be sensitively and selectively detected, often by direct observation of 1H values. There are a number of conditions on the binding kinetics which must be met, and systems with multiple binding sites generally cannot be analyzed. The large number of different NMR approaches which can be used, often only under special conditions of exchange, complicates planning of NMR studies of ligand-macromolecule interactions. However, once the characteristics of binding affinity and exchange rate have been determined, it is usually possible to apply NMR spectroscopy to obtain information about the binding. The instrumental demands for carrying out ligand-macromolecule interactions are generally not more than those required for studies of the macromolecules alone.

[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.

The mycorrhizal relationship of multinucleate rhizoctonias from non-orchids with Microtis (Orchidaceae).

Multinucleate rhizoctonias isolated from the roots of non-orchid plants were used in symbiotic germination tests with seed of 18 orchid species from 10 genera. The rhizoctonias only stimulated germination of Microtis. Investigation of the natural mycosymbionts of adult Microtis failed to yield fungi similar to the original multinucleate rhizoctonias: 27 Microtis plants collected at seven sites in the Sydney region yielded 26 binucleate rhizoctonias tentatively identified as Tulasnella calospora (Boudier) Juel and one very slow growing multinucleate rhizoctonia tentatively identified as Sebacina vermifera Oberwinkler. Fungi closely resembling the original multinucleate rhizoctonias were isolated by baiting the soil with subterranean clover (Trifolium subterraneum L.) plants at three of the seven Microtis sites.

Ultrastructural evidence for the identity of some multinucleate rhizoctonias.

The ultrastructure of the pore cap in ten multinucleate rhizoctonias, endophytes of non-orchids and of Microtis (Orchidaceae), was compared with that in isolates of four Sebacina species. The pore cap in all the rhizoctonias was an imperforate, disc-like structure, Slightly smaller in diameter than the flange forming the septal pore canal. The cap was formed by two Bat lamellae continuous with, but more electron-dense than, the membranes of the endoplasmic reticulum. The lamellae enclosed a lumen containing a deposit of electron-dense material. The pore cap in the rhizoctonias was indistinguishable from that in an isolate of Sebacina vermifera Oberwinkler. In contrast, the pore caps in isolates of S. calcea (Pers.: Fr.) Bres., S. umbrina Rogers and S. grisea (Pets.: Fr.) Bres., which were also imperforate and contained a band of electron dense material, were strongly dome-shaped and extended from one side of the flange to the other.

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.

Vitamin retention in cook/chill and cook/hot-hold hospital food-services.

The vitamins with the greatest losses during hot-holding of food (> 10% after 2 hours) are vitamin C, folate, and vitamin B-6; retinol, thiamin, riboflavin, and niacin appear to be relatively stable. The 66 studies reviewed in this article give inadequate information on the losses of many other vitamins. In cook/chill food-services, substantial losses of sensitive vitamins occur during each of the chilling, storage, and reheating stages. Different reheating methods have similar effects on the amount of vitamin retention. Losses of vitamin C and folate can be greater than 30% when food is reheated after storage for 24 hours at 3 degrees C. Current research indicates that under normal operating conditions, with hot-holding limited to less than 90 minutes, vitamin retention is better in a conventional food-service than in a cook/chill system.

Case study: cross-gender preoccupations with two male children with autism.

Persons with autism frequently exhibit circumscribed interests and unusual preoccupations. In this case study, two young males with autism are presented who have preoccupations with feminine gender-stereotyped activities and objects. These types of preoccupations in children with autism have not been reported in the literature, but may be more prevalent than realized due to parental underreporting given the negative stigma associated with feminine interests in young boys. The development of gender identity in young children with autism has rarely been addressed in the literature. It seems unlikely that these two cases can be categorized as gender identity disorders. Understanding these preoccupations in the context of autism rather than focusing on the gender identity issues has important implications for treatment. These cases point to the need for further study of the complex interplay of environmental and neurobiologic factors affecting gender identity roles and preoccupations in autism.

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.

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.

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.