Brain HMPAO-SPECT and ocular microangiopathic syndrome in HIV-1-infected patients

OBJECTIVE: The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome. METHODS: We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semi-quantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and, retinal cotton-wool spots were counted. CD4 count, neopterin, beta 2-microglobulin (beta 2M), haemoglobin, and age were determined as putative confounding variables. RESULTS: Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3 +/- 0.5 (mean +/- s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1 +/- 0.6 and mean cotton-wool spot count was 1.1 +/- 0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5 +/- 0.3 and mean cotton-wool spot count was 4.9 +/- 1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r = 0.72; P < 0.001) and number of cotton-wool spots (r = 0.78; P < 0.001), whereas only a slight association with staging of HIV disease was found (P = 0.052). Analysis of covariance controlling for CD4 count neopterin, beta 2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P < 0.001) and the conjunctival sludge rating (P < 0.001). CONCLUSION: There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system [corrected].     

Effect of nadroparin, a low-molecular-weight heparin, on clinical and angiographic restenosis after coronary balloon angioplasty: the FACT study. Fraxiparine Angioplastie Coronaire Transluminale

BACKGROUND: Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty. METHODS AND RESULTS: In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10,250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37+/-0.66 mm, 51.9+/-21.0%) did not differ from the corresponding values in the control group (1.48+/-0.59 mm, 48.8+/-18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%). CONCLUSIONS: Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.     

Acquisition of the mental state verb know by 2- to 5-year-old children

The production of the cognitive internal state word know by four 2- to 5-year-old children and their parents was examined. The levels of meaning of cognitive words can be categorized hierarchically along the dimensions of conceptual difficulty and abstractness (see Booth & Hall, 1995). The present study found that children and their parents expressed low levels of meaning less frequently, whereas they expressed high levels of meaning more frequently as a function of age. The children's use of know was also correlated positively with (1) their number of different words produced suggesting that cognitive words are related to more general semantic processes, and (2) with parental use of those same cognitive words suggesting that parental linguistic input may be an important mechanism in cognitive word acquisition. Finally, young children tended to use know more to refer to themselves than to refer to others, whereas their parents tended to use know equally to refer to self and others. The importance of cognitive words in a theory of language acquisition is discussed.     

Optic chiasm astrocytomas of childhood. 1. Long-term follow-up

There are many in vivo animal models for studying airway mucus secretion and hypersecretion, each with advantages and disadvantages. Use of a particular test system will depend upon the aspect of secretion to be modelled. Airway hypersecretory diseases exhibit chronic mucus hypersecretion, of which the clinical impact is predominantly in the distal airways. The majority of documented test preparations study acute secretion, invariably using tracheal preparations, but have been invaluable in elucidating the normal physiology of airway mucus secretion. Chronic models of the hypersecretory state in the distal airways have been developed, but are predominantly histologic in nature (for example quantification of increased goblet cell number). There are few investigations of mucus hypersecretion. Examination of the 'antisecretory' potential of pharmaceutical compounds has been investigated predominantly in chronic histologic models with the drug being given 'prophylactically' rather than 'therapeutically'. Refinement of chronic hypersecretory models should lead to elucidation of the connection between airway irritation, inflammation, MUC gene expression, mucous cell hyperplasia/metaplasia, airway hypersecretion and bronchial hypersecretory disease.     

Requirement of cysteine-rich repeats of the Fas receptor for binding by the Fas ligand

The Fas receptor is a member of a family of cell death receptors, including tumor necrosis factor receptor I (TNFR I), death receptor 3 and 4 (DR3 and DR4), and cytopathic avian receptor 1 (CAR1). The Fas receptor is composed of several discrete domains, including three cysteine-rich domains (CRDs), a transmembrane domain, and an intracellular domain responsible for transmitting an apoptotic signal. While the mechanism of Fas-mediated cell death has become elucidated, the requirements for Fas ligand binding to the receptor have not been fully defined. Using a series of chimeric Fc-receptor fusion proteins between the human Fas receptor and TNFR I, each cysteine-rich domain of Fas was found to be required for interaction with the Fas ligand. Interestingly, TNFR I CRD1 could partially substitute for the Fas CRD1. The importance of this domain was underscored by the analysis of a Fas extracellular mutation (C66R), which resulted in a complete loss of ligand binding. This mutation was cloned from a human patient suffering from Canale-Smith syndrome, which is characterized by autoimmunity resembling that observed in the lpr and lprcg mice. The localization of essential ligand binding domains in the Fas receptor correlated exactly with the ability of the Fas receptor fusion proteins to prevent cell death mediated by the Fas ligand.     

Stress fracture of the sternum: an unusual injury?

Stress fracture of the sternum is a rare condition which presents as acute anterior chest pain after repetitive upper-body exercise. Two case reports are presented and it is postulated that this is an often underdiagnosed condition which should be considered in the differential diagnosis of acute chest pain in the athlete. Awareness of the injury together with meticulous clinical examination supported by good quality radiographs or isotope bone scan may lead to an increase in the diagnosis of this injury.     

Alterations in reflex function contributing to syncope: orthostatic hypotension, carotid sinus hypersensitivity and drug-induced dysfunction

Orthostatic hypotension and related neurologic symptoms are frequently encountered in clinical practice. The maintenance of appropriate blood pressure and heart rate responses upon assuming the upright posture are dependent upon: 1. intact mechanical (venous valves) mechanisms, 2. functioning arterial and cardiopulmonary baroreceptors, 3. normal peripheral neural pathways, 4. normal central neural integration, and 5. appropriate neurohormonal secretion. Dysfunction at one or more of these loci may facilitate the occurrence of orthostatic hypotension and syncope. In general, the mechanisms of orthostatic hypotension may be divided into three categories. In the first category, processes interfere with normal compensatory responses to upright posture. Examples of this mechanism include age related autonomic changes, diabetic neuropathy and central nervous system disease such as Shy-Drager syndrome. The second principal mechanism involves overwhelming otherwise normal reflexes by an intense orthostatic stimulus. An obvious example of this mechanism is syncope related to hemorrhage. A final category of orthostatic hypotension relates to interference with reflex responses by drugs that may limit vasoconstriction, heart rate or cardiac output adjustments or exaggerate venous pooling. These are commonly used medications such as vasodilators, beta-adrenergic blockers and nitrates. The treatment of orthostatic hypotension revolves around the recognition of underlying causes or contributing factors amenable to correction or avoidance. Other helpful treatment options include nocturnal head-up tilting and mineralocorticoids, both of which help to expand blood volume. Many other therapeutic agents have been tried in small and selected patient populations, often with disappointing results. While many of the drugs available (phenylephrine, ephedrine, tyramine, dihydroergotamine) can improve upright blood pressure, side effects are common, and supine hypertension is problematic in many patients. Interventions of this type should be carefully initiated in a monitored setting. The carotid sinus is an important component of a neural control system responsible for heart rate and blood pressure homeostasis. Excessive heart rate and blood pressure responses to distortion of the carotid sinus are the basis for the carotid sinus syndrome (CSS). Patients with CSS tend to be elderly males and local pathology in the neck is frequently involved. Atherosclerotic coronary artery disease and hypertension are important clinical correlates. Two major categories of carotid sinus hypersensitivity (CSH) are recognized: cardioinhibitory and vasodepressor. Cardioinhibitory CSH is the most common, and in its purest form consists of sinus bradycardia or arrest, asystole or AV block during carotid sinus massage. This vagally-mediated response is eliminated by atropine. Cardiac pacing is nearly universally successful in preventing severe symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)     

Evaluation of the clinical impact of endoscopic ultrasonography in gastrointestinal disease

A total of 120 gastro-intestinal tracts and 960 faecal samples were examined to assess the prevalence and seasonal changes in the gastro-intestinal helminth parasites of Red Sokoto (maradi) goats slaughtered at Ibadan between May 1991 and April 1992. Egg types of strongyles, Strongyloides, Trichuris, Skrjabinema, Dicrocoelium and Moniezia were encountered in 93%, 83%, 44%, 0.9%, 2.3% and 31% of the faecal samples respectively. However, only strongyle, Strongyloides and Trichuris eggs occurred in large numbers and were more common during the rainy season than in the dry season. The parasites recorded and their prevalences were Haemonchus contortus (90.0%), H. ovis (5.0%), Strongyloides papillosus (80.8%), Trichostrongylus colubriformis (78.3%), T. axei (69.2%), Trichuris ovis (72.5%), T. globulosa (38.3%), Oesophagostomum columbianum (67.5%), Cooperia curticei (58.3%) Gaigeria pachyscelis (40.8%), Skrjabinema ovis (5.0%), Nematodirus battus (5.8%), Moniezia expansa (29.2%), M. benedeni (10.0%), Paramphistomum spp. (5.0%) and Cysticercus tenuicollis (33.3%). Haemonchus ovis is reported for the first time in Nigeria. Mixed infections were most prevalent. Young goats were more commonly infected and had higher worm counts than adult goats. Only Haemonchus, Trichostrongylus, Strongyloides and Cooperia spp. occurred in large numbers. Irrespective of the age of the goats, higher worm counts were generally encountered during the rainy season than in the dry season. The results are discussed in relation to the control of helminthiasis in grazing animals in Nigeria.     

Unit risk estimates for airborne arsenic exposure: an updated view based on recent data from two copper smelter cohorts

The current unit risk for airborne arsenic, 4.29 x 10(-3), was established by the EPA in 1984. Using updated results from a cohort mortality study on Tacoma smelter workers and recent findings from a cohort study of 3619 Swedish smelter workers, new unit risk estimates were developed for the respective cohorts. Methods were analogous to those used by the EPA in 1984, and all estimates were derived under an absolute risk model. A new unit risk 1.28 x 10(-3), was estimated for the Tacoma smelter cohort which was a factor of 5 less than the EPA's earlier estimate, and a direct result of radically revised exposure estimates. A unit risk of 0.89 x 10(-3) was estimated from the Swedish study. Pooling these new unit risk estimates with the EPA's earlier estimates from the Montana smelter cohort yielded a composite unit risk of 1.43 x 10(-3). Based on this estimate, the present unit risk may overestimate the effects of airborne arsenic by a factor of 3. A need to update the unit risk for airborne arsenic and the collateral IRIS database is evident from the results.