Microcomputer Automated System for Measuring Systolic Time Intervals in Response to Exercise and a Psychophysiological Task

A microcomputer automated system for measuring systolic time intervals is described. Electrocardiogram, phonocardiogram, and carotid pulse tracings were measured in 38 healthy male subjects during baseline conditions and during either exercise on a bicycle ergometer or a video-game task. These measurements were recorded on both a traditional 3-channel ECG recorder and the computerized system. Both methods of recording systolic time intervals were independently scored by two different experimenters. In this way, interrater reliability of hand-scoring, intermethod reliability between hand-scoring versus computer-scoring, and interrater reliability of computer-scoring could be assessed. The interrater reliabilities of hand-scored systolic time intervals were generally above .90, ranging from .73 for left ventricular ejection time to .99 for R-R intervals of the ECG, with a mean of .92. The intermethod reliability of the computer versus hand-scored systolic time intervals also proved to be generally above .90, ranging from .76 for S1-S2 components of the phonocardiogram to .99 for R-R, with a mean of .94. The interrater reliabilities of the computer-scored systolic time intervals were all above .90, ranging from .93 for S1-S2 to .99 for R-R, with a mean of .98. These data indicate that the computerized method of scoring systolic time intervals is at least as reliable as the more traditional scoring of paper tracing.     

Attenuation of pathological tremors by functional electrical stimulation II: Clinical evaluation

In this study we evaluated a technique for tremor suppression with functional electrical stimulation (FES), the technical details of which were described in the previous paper. Three groups of patients were investigated: those with essential tremor, parkinsonian tremor, and cerebellar tremor associated with multiple sclerosis. In each group, tremor was attenuated by significant amounts (essential tremor: 73%; parkinsonian tremor: 62%; cerebellar tremor: 38%). These attenuations were in good accord with predictions based on the dynamic analyses and filter designs derived in the previous paper. With filters “tuned” to the lower mean tremor frequency encountered in the cerebellar patients, more attenuation was possible in this group as well. We identified some practical limitations in the clinical application of the technique in its present form. The most important was that in daily use, only one antagonist pair of muscles can realistically be controlled. At first sight, this restricts the usefulness of the system to patients with single-joint tremors. However, the concomitant use of mechanical orthoses may broaden the scope of application.     

RESPONSE CONTINGENCY AND HUMAN GASTRIC ACIDITY

The purpose of this study was to investigate the relationship between avoidance behavior of human subjects and gastric acid changes. An intragastric radio transmitter was employed to record stomach acid secretion rates. The subjects were divided into two groups. The members of the Response-Contingent (RC) group were led to believe that they would be able to avoid a strong electric shock during the Test phase of their session. In the No-Response (NR) group, subjects were correctly told that they would be without means of avoiding shock. The results demonstrated that (a) subjects could not be differentiated according to gastric acid secretion rate strictly on the basis of whether or not they made an avoidance response to an aversive stimulus; (b) a non-significant majority of subjects in both groups exhibited decreased gastric acid secretion rates during the Test phase; and (c) both groups showed a significantly faster rate of gastric acid secretion during the Post-Test phase than during the Test condition.     

Molecular identification of pathogenetic IdLNF+1 autoantibody idiotypes derived from the NZBxSWR F1 model for systemic lupus erythematosus

The acceleration of nephritis in SNF(1) mice by CD4(+) T-cell clones reactive with a nephritogenic idiotype, Id(LN)F(1) [1], as well as the ability of anti-Id(LN)F(1) antisera to down-regulate the production of Id(LN)F(+)(1) immunoglobulin (Ig) in vivo and delay nephritis [2], suggests that dysregulation of this idiotype may contribute to the development of SNF(1) nephritis. Herein, we show that a monoclonal Id(LN)F(1)-expressing antibody, 540, significantly (P< or = 0.01) stimulated Id(LN)F(1)-reactive T-cell clones B6 and D2 to proliferate, while other Id(LN)F+1 antibodies did not. Further, injection of 540-producing hybridoma cells into nonautoimmune (SWRxBalb/c)F(1) mice resulted in the deposition of Id(LN)F(+)(1) Ig in the kidneys, in a pattern indicative of early nephritis. To identify the pathogenetic Id(LN)F(1) epitope(s) at the molecular level, we compared the deduced amino acid sequences of the heavy and light chain variable regions of pathogenetic and non-pathogenetic Id(LN)F(1)-expressing Igs 540, 317, and 533. Two overlapping peptides derived from the V(H) sequence of 540 (aa 54-66 and 62-73), which both contain the triple basic amino acid motif K(X)K(X)K, stimulated SNF(1) T cells and T-cell clones B6 and D2. These results further support the involvement of a subset of Id(LN)F(1)-expressing Ig in SNF(1) nephritis.     

A critical function for type I interferons in cancer immunoediting

'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in this process, the involvement of type I interferons (IFN-alpha/beta) has not been elucidated. We now show that, like IFN-gamma, endogenously produced IFN-alpha/beta was required for the prevention of the growth of primary carcinogen-induced and transplantable tumors. Although tumor cells are important IFN-gamma targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma.     

Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy

The clinical progression of Duchenne muscular dystrophy (DMD)patients with deletions can be predicted in 93% of cases bywhether the deletion maintains or disrupts the translationalreading frame (frameshift hypothesis). We have identified andstudied a number of patients who have deletions that do notconform to the translational frame hypothesis. The most commonexception to the frameshift hypothesis is the deletion of exons3 to 7 which disrupts the translational reading frame. We identifieda Becker muscular dystrophy (BMD) patient, an intermediate,and a DMD patient with this deletion. In all three cases, dystrophinwas detected and localized to the membrane. One DMD patientwith an inframe deletion of exons 4–18 produced no dystrophin.One patient with a mild intermediate phenotype and a deletionof exon 45, which shifts the reading frame, produced no dystrophin.Two patients with large inframe deletions had discordant phenotypes(exons 3–41, DMD; exons 13–48, BMD), but both produceddystrophin that localized to the sarcolemma. The DMD patient,113, indicates that dystrophin with an intact carboxy terminuscan be produced in Duchenne patients at levels equivalent tosome Beckers. The dystrophin analysis from these patients, togetherwith patients reported in the literature, indicate that morethan one domain can localize dystrophin to the sarcolemma. Lastely,the data shows that although most patients show correlationof clinical severity to molecular data, there are rare patientswhich do not conform.     

烧伤的流行病学、人口统计学及结局特点

老年人的群体在不断扩大，而他们烧伤的发病率和死亡率都要比年轻人高。最近的一项病例回顾研究分析了一家烧伤中心7年来住院患者的资料，结果显示，1557位住院患者中有221位（11％）年龄在59岁以上（含59岁）。其中有97位（44％）是女性，反映出老年患者中女性比例较高。     

Hearing impairment as an early sign of alpha‐mannosidosis in children with a mild phenotype: Report of seven new cases

Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDE^R) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management.