Longer Disease Course Research Articles

Disease Duration Determines Canine Distemper Virus Neurovirulence

The Morbillivirus hemagglutinin (H) protein mediates attachment to the target cell. To evaluate its contribution to canine distemper virus neurovirulence, we exchanged the H proteins of the wild-type strains 5804P and A75 and assessed the pathogenesis of the chimeric viruses in ferrets. Both strains are lethal to ferrets; however, 5804P causes a 2-week disease without neurological signs, whereas A75 is associated with a longer disease course and neurological involvement. We observed that both H proteins supported neuroinvasion and the subsequent development of clinical neurological signs if given enough time, demonstrating that disease duration is the main neurovirulence determinant.

Patterns of levodopa response in Parkinson's disease: a clinico-pathological study

Patients with Parkinson's disease who develop disabling levodopa-induced motor fluctuations have a stronger therapeutic response than those who experience a more modest but stable response. A difference in the histopathological lesion between the two groups might be responsible. Case records from 97 patients with pathologically proven Parkinson's disease were reviewed to determine the pattern of levodopa response. Pathological findings for fluctuating and non-fluctuating cases were compared. Patients with motor fluctuations had a younger age of onset and longer disease course (P < 0.001), although mean age at death was almost the same. Four milestones of advanced disease (frequent falls, visual hallucinations, cognitive disability and need for residential care) occurred at a similar time from death in each group; this interval was not proportionate to the disease duration. There were no significant differences in the severity or distribution of Lewy body or other pathologies. Irrespective of the pattern of levodopa response, patients reach a common pathological endpoint at a similar age, and the duration and manifestations of end-stage disease are alike. A non-linear or exponential time relationship may govern the late clinical and pathological progression of Parkinson's disease.

Analysis on relevant factors of hyperthyroidism complicating hyperthyroid heart disease

目的 探讨甲状腺功能亢进性心脏病(甲亢心)易发的相关因素及临床特点.方法采用向前逐步筛选变量法对48例甲亢心行Logistic多因素回归分析,内容包括性别、年龄、病程、病情、发病情况、是否规律治疗及有无其他并发症.结果甲亢心的发生与患者年龄、病程、病情、是否规律治疗密切相关,甲亢心的心脏表现呈多样性,以心律失常多见,尤以房颤(75%)为主.结论甲状腺功能亢进症(甲亢)并发甲亢心的因素较多,对于年龄偏大、病程长、病情重、未行规律治疗的甲亢患者要重视甲亢心的发生,可给予必要的预防与治疗。

Sleep-disordered breathing and respiratory failure in acid maltase deficiency.

Sleep-disordered breathing (SDB) and respiratory failure (RF) are complications of acid maltase deficiency (AMD), a rare hereditary myopathy. To define the relationship between lung and respiratory muscle function, to establish incidence and patterns of SDB, and to determine daytime predictors of SDB. Sitting and supine lung and respiratory muscle function tests were obtained in 27 subjects with juvenile and adult AMD (aged 39 +/- 19 years) and compared with outcomes of polysomnography. Ventilatory restriction was present in 17/27 subjects. Inspiratory vital capacity (IVC) correlated (p < 0.005) with peak inspiratory muscle pressure (PIP, R = 0.61), respiratory muscle strain (P(0.1)/P(0.1max), R = -0.68), and gas exchange by day (PaO(2): R = 0.71; PaCO(2): R = -0.64) and night (SaO(2): R = 0.73; P(tc)CO(2): R = -0.75). Diaphragm weakness (DW) was present in 13 subjects, 10 of whom had hypercapnic RF (PaCO(2) 65 +/- 7 mm Hg), and was associated with longer disease course. SDB was found in 13 subjects, 12 with DW. It was characterized by REM-sleep hypopneas that, as ventilatory restriction worsened, were complemented by hypoventilation (P(tc)CO(2) > 50 mm Hg) first in REM sleep, then in non-REM sleep (p < 0.005). SDB was predicted by DW (sensitivity 80%, specificity 86%) and nocturnal hypoventilation by IVC < 40% (sensitivity 80%, specificity 93%). Noninvasive ventilation, instituted for daytime respiratory failure or nocturnal hypoventilation, normalized daytime and nocturnal gas exchange (p < 0.005). Vital capacity correlates with respiratory muscle function in AMD. Diaphragm weakness is the major cause of SDB and RF. SDB and nocturnal hypoventilation are predictable from daytime function tests.

Ganancia, pérdida y concordancia en el diagnóstico de asma entre neumólogos y no neumólogos

To determine and analyze the degree of agreement and disagreement in the diagnosis of bronchial asthma (BA) by respiratory disease specialists and generalists in regional hospital and primary care settings. Ninety-six outpatients (16 to 70 years of age) were studied; all had been assigned a diagnosis of BA by the referring physician or by the respiratory disease specialist. We recorded 1) clinical symptoms, determining the initial probability of a diagnosis (IPD)of BA to be high, medium or low; 2) results of spirometry and bronchodilator testing (BDT), peak flow variability and methacholine challenge testing; 3) prick test results, eosinophil levels and total serum IgE levels. Three diagnoses were recorded: the initial diagnosis (ID) by the referring physician to whom follow-up data were unavailable; diagnosis by the respiratory disease specialist based only on clinical symptoms (RSS); and the final diagnosis(FD). To arrive at a FD of BA, it was necessary to have a high or medium IPD and a positive BDT. A Kappa test was used to analyze the degree of agreement among the three diagnoses. Group features associated with greater or lesser agreement were analyzed by chi-square tests and analysis of variance. Agreement was acceptable between RSS and FD (K = 0.63) but very low between ID and RSS and between ID and FD. In the latter two cases, agreement was greatest for patients diagnosed in hospital and for those with high IgE levels (p < 0.05), with high IPD, longer course of disease and a history of asthma (p < 0.01) (odds ratio =59.8). Diagnostic disagreement occurred mainly for patients for whom a BA diagnosis was gained later, the of under-diagnosis being 39%. The patients involved visited the physician only because they had observed an isolated symptom related to asthma (odds ratio = 119) and to arrive at a diagnosis bronchomotor tests other than BDT were required (p < 0.01). a) The degree of agreement for a diagnosis of BA is low. b)The functional profile of patients for whom diagnostic agreement exists differs from that of patients for whom diagnosis is gained through testing. c) In the context of this study, a high rate of under-diagnosis is evident.

Fatal familial insomnia: clinical features and molecular genetics.

Fatal familial insomnia (FFI) is an autosomal dominant prion disease clinically characterized by inattention, sleep loss, dysautonomia, and motor signs and pathologically characterized by a preferential thalamic degeneration. FFI is linked to a missense mutation at codon 178 of the prion protein gene, PRNP, coupled with the presence of the codon methionine at position 129, the locus of a methionine-valine polymorphism. Homozygotes at codon 129, expressing methionine also in the nonmutated allele, have a shorter disease course (often less than 1 year), prominent sleep and autonomic disturbances at disease onset, and pathology restricted to the thalamus. Heterozygotes at codon 129, expressing valine in the nonmutated allele, have a longer disease course (often longer than 1 year), ataxia and dysarthria at disease onset, and lesions widespread to cerebral cortex. Both in the thalamus and in the cortex, the limbic structures are those most consistently and severely involved: the anterior ventral and mediodorsal thalamic nuclei, the cingulate gyrus, and the orbitofrontal cortex. FFI is thus a prion disease selectively damaging the thalamocortical limbic structures. Loss of sleep, sympathetic hyperactivity, and flattening of vegetative and hormonal circadian oscillations characterize FFI and result from a homeostatic imbalance caused by the interruption of the thalamocortical limbic circuits, the phylogenetically most advanced structures involved in the control of the sleep-wake cycle and the body's homeostasis. The selective atrophy of the limbic thalamus that characterizes FFI might be due to the binding of FFI toxic PrP or PrPres to specific receptors on thalamolimbic neurons.