Oral hairy leukoplakia in vertically and horizontally acquired HIV infection

Two boys aged 7 and 8 years, respectively, with oral hairy leukoplakia as the sole clinical sign indicative for HIV infection are reported.     

Atypical Kawasaki disease with peripheral gangrene and myocardial infarction: Therapeutic implications

We describe a 2-month-old girl with atypical Kawasaki disease (KD) complicated by peripheral gangrene and myocardial infarction. Peripheral ischaemia leading to gangrene is a rare but serious complication of KD in infants younger than 7 months of age. Treatment has been targeted at reducing arterial inflammation, arteriospasm and thrombosis. We report the first patient with incomplete KD and peripheral ischaemia in whom therapy with prostaglandin E1 (PGE1) as vasodilating and antithrombotic agent appeared successful, restoring hand and foot perfusion without significant long-term sequelae. However, PGE1 could have supported development of myocardial infarction by shunting blood away from ischaemic areas distal to a giant coronary artery aneurysm with beginning thrombosis.Conclusion Atypical KD with peripheral gangrene appears to react favourably to treatment with PGE1, but needs careful monitoring to detect early signs of cardiac ischaemia.     

Renal transplantation and osteoporosis

A cross sectional study assessed the bone mineral density (BMD) of 20 young adult patients who received a renal transplantation in childhood. The BMD of the lumbar spine, mainly trabecular bone, and of the total body, mainly cortical bone, were measured and expressed as an SD score. Fourteen patients (70%) had a BMD SD score of the lumbar spine below -1, of whom six patients were below -2. Fifteen patients (75%) had a BMD SD score of the total body below -1, of whom seven patients were below -2, Both trabecular and cortical bone appeared to be involved in the osteopenic process. The cumulative dose of prednisone was inversely correlated to both lumbar spine and total body BMD SD score. In a multiple regression analysis the cumulative dose of prednisone appeared to be the only factor with a significant effect on BMD SD score. Most young adult patients who had received a renal transplantation in childhood had moderate to severe osteopenia. Corticosteroid treatment played a major part in the development of osteopenia in these patients.     

Congenital acatalasemia: a study of neutrophil functions after provocation with hydrogen peroxide

Five Swiss subjects with hereditary acatalasemia (4 homo-, 1 heterozygous) were studied by a series of neutrophil function tests. H2O2 was added to a polymorphonuclear neutrophil leukocyte-suspension to produce a metabolic stress; neutrophil functions related to membrane deformation were subsequently found to be depressed, i.e., chemotaxis, membrane potential, and chemiluminescence. This mechanism might be one pathogenetic factor in the formation of mucosal ulcers in acatalasemic individuals.     

Clonidine toxicity revisited

The incidence of clonidine overdose is increasing, yet there is a paucity of new information regarding treatment options for clonidine toxicity. Reported treatment approaches vary widely, demonstrating the lack of science on which current treatment is based. Available research needs to be reassessed. Neurotransmitters, receptors, endogenous opioids, and baseline sympathetic tone determine the clinical response to clonidine as well as the potential response to drug therapy following clonidine overdose. This article reviews aspects of clonidine toxicity that need to be further investigated. Multicenter research trials will be required to evaluate new treatment options.     

Regulation of p53: intricate loops and delicate balances

The p53 tumor suppressor protein provides a major anti-cancer defense mechanism, as underscored by the fact that the p53 gene is the most frequent target for genetic alterations in human cancer. Recent work has led to the realization that p53 lies at the hub of a very complex network of signaling pathways, which integrate a variety of intracellular and extracellular inputs. Part of this network consists of an array of autoregulatory feedback loops, where p53 exhibits very intricate interactions with other proteins known to play important roles in the determination of cell fate. We discuss two such loops, one involving the beta catenin protein and the other centering on the Akt/protein kinase B. In both cases, the central module is the interplay between p53 and the murine double minute 2 (Mdm2) protein, which inactivates p53 and targets it for rapid proteolysis. Whereas deregulated beta catenin can lead to Mdm2 inactivation and p53 accumulation, active p53 can promote the degradation and downregulation of beta catenin. Similarly, Akt can block p53 activation by potentiating Mdm2, whereas activated p53 can tune down Akt in several different ways. In each case, the actual output of the loop is determined by the delicate balance between the opposing effects of its different components. Often, this balance is dictated by additional signaling processes that occur simultaneously within the same cell. Genetic alterations characteristic of cancer are capable of severely distorting this balance, thereby overriding the tumor suppressor effects of p53 in a manner that facilitates neoplastic conversion.     

Psychological test performance during experimental challenge to toluene and n-butyl acetate in cases of solvent-induced toxic encephalopathy

OBJECTIVES: This study determined whether performance in neurobehavioral tests deteriorates during subjectively annoying chemical challenge below known neurotoxic thresholds among persons with toxic encephalopathy with subjective hypersensitivity to chemicals. METHODS: Subjects with symptoms and previous neuropsychological test results compatible with toxic encephalopathy (TE) of either type 2A (N=12) or 2B (N=12) and unexposed referents (N=12) were challenged in an exposure chamber. In a counterbalanced design, the subjects were exposed on 2 occasions to increasing air concentrations of n-butyl acetate and toluene at levels well below the thresholds for neurotoxic effects. Attention and motor speed tests were given (i) in room air outside the chamber before the challenge, (ii) in room air inside the chamber before the exposure, (iii) at 12 ppm (44 or 56 mg/m3), and (iv) at 48 ppm (at 180 or 228 mg/m3). RESULTS: For both substances the TE groups showed a slight increase (deterioration) in the simple reaction-time task during chemical exposure, but not in the complex reaction-time task or in the digit symbol test of the Wechsler Adult Intelligence Scale. Contrary to reference subjects, the TE subjects did not show any improvement or learning effect in the digit symbol test over the chamber phases. n-Butyl acetate tended to affect cognitive functioning more obviously than toluene did. Suggestion or expectancy effects were not observed in any group in the clean-air baseline conditions. CONCLUSIONS: The results do not support the notion that men with subjective hypersensitivity to chemicals would be more affected than healthy men regarding cognitive functioning during annoying solvent exposure below thresholds for acute neurotoxic effects.     

Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age

The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate.