Neuropsychological stability over two years in asymptomatic carriers of the Huntington's disease mutation.

This study examined whether neuropsychological changes emerge over time in asymptomatic adults who have the Huntington's disease mutation. We also evaluated whether scores on cognitive tests or psychological symptom scales varied as a function of CAG repeat length or proximity to disease onset. Twenty two healthy "mutation positive" and 37 "mutation negative" adults completed cognitive tests and psychological rating scales before disclosure of their genetic test results and on an annual basis thereafter. Repeated measures ANOVAs analysed differences between the two groups over three assessments. Correlations of cognitive and psychological symptom test scores with estimated number of years to disease onset and CAG repeat length were computed. The two groups did not differ at study entry; nor did they differ in the rate of change over time. Tests of sustained attention and mental speed correlated with estimated years to disease onset, but not with repeat length. As a group, clinically asymptomatic adults with the Huntington's disease mutation do not display neuropsychological deficits when studied over a two year interval. However, persons who are likely nearing clinical onset of Huntington's disease may develop minor deficits in selected cognitive domains before they reach threshold for diagnosis.     

Educational support groups of patients with ankylosing spondylitis: a preliminary report

Educational support groups (ESGs) for patients with ankylosing spondylitis were found to significantly (P less than 0.01) increase knowledge about the disease and its treatment. Compliance of participants with their prescribed exercise programs was improved, although the improvement did not achieve statistical significance. Compliance with prescribed application of heat to joints was not changed. Control patients showed no substantial changes in knowledge or compliance. Although analysis of pretest and posttest responses on a questionnaire did not indicate that the ESGs enhanced the patients' ability to cope with ankylosing spondylitis or their perception of the adequacy of family relationships with regard to the disease, verbal feedback concerning these areas was positive in most cases. Patients did not express negative feelings about the thought of meeting another person with ankylosing spondylitis whose disease was less severe or whose coping ability was greater or less than their own. Two patients who initially believed that they would feel threatened if they were to meet a more severely ill patient relinquished that concern after ESG participation.     

Effects of indomethacin and prostacyclin on isolated human pial arteries contracted by CSF from patients with aneurysmal SAH

In small human cerebral arteries preincubated with indomethacin, contractions induced by cerebrospinal fluid (CSF), from patients with subarachnoid hemorrhage were markedly increased. Also contractions induced by noradrenaline, but not 5-hydroxytryptamine, were augmented. Prostacyclin and its metabolite 6-keto-prostaglandin (PG)E1 reversed the contractions induced by CSF, as well as by noradrenaline, 5-hydroxytryptamine, and PGF2 alpha. The findings suggest that these substances are able to counteract the influence of vasoconstrictor material in hemorrhagic CSF. If the capacity to synthesize these "protective" arachidonic acid metabolites is reduced, the resulting imbalance between contractile and relaxant forces acting on the vessel wall may lead to sustained cerebral vasoconstriction.     

PHS perspectives on misconduct in science.

The Public Health Service (PHS) has undertaken a major effort to develop improved policies and procedures for dealing with misconduct in its research programs. Included in the definition of "misconduct" are the violation of Federal laws, regulations, or policies governing research or research training conducted, funded, or regulated by the Department of Health and Human Services; breaches of professional ethics that raise serious questions about an investigator''s or institution''s scientific or fiscal integrity; and serious failures to comply with other terms or conditions of an award. Recent incidents of falsification or misrepresentation of data and failure to comply with requirements for protection of human and animal subjects of research represent only a fraction of all research projects. However, they are troubling evidence that the traditional safeguards of science are not sufficient to prevent and detect willful wrongdoing. Research agencies, awardee institutions, and individual investigators have a collective responsibility to prevent misconduct in public research programs. The agencies and institutions, in turn, must deal promptly and equitably with allegations or evidence of misconduct. Individual research institutions and their professional organizations have developed policy statements affirming their responsibility for the integrity of the research enterprise and proposing specific procedures for dealing with incidents of misconduct. The National Institutes of Health currently serves as lead agency for a parallel PHS effort that includes a statement of general policies and principles, to be augmented by specific procedures for awarding agencies, regulatory agencies, and PHS intramural programs, as well as procedures for information sharing and joint investigations.     

100 years of intubation anesthesia. William Macewen, a pioneer of endotracheal intubation

Endotracheal anaesthesia with the help of orotracheal intubation is 100 years old. In 1880, William Macewen was the first to describe and to perform that technique. In his paper entitled "clinical observations on the introduction of tracheal tubes by the mouth instead of performing tracheotomy or laryngotomy' he describes in addition two cases of endotracheal intubation lasting at least 36 h. He can, therefore, be said also to have performed the first long-time intubation.     

Loss of heterozygosity for the short arm of chromosome 11 (11p15) in human milk epithelial cells immortalized by microinjection of SV40 DNA.

We have developed, by microinjection of SV40 DNA into human milk epithelial cells, a new mammary cell line, Hu-MI, which exhibits the phenotype of luminal cells or so-called "breast cancer precursor cells." This cell line retains the phenotype of primary cells as demonstrated by the expression of keratins 18 and 19 and of polymorphic epithelial mucins. However, the cells do not grow in agar after more than 80 passages, nor do they form tumors in nude mice. Established cells contain 2 copies of SV40 DNA integrated into the cellular genome and up to 14 copies of free SV40 DNA. A deletion of the short arm of chromosome 11 (11p15) including the c-Ha-ras and the beta-globin genes was found in the immortalized cells when the DNA from these cells was compared to the DNA from peripheral blood mononuclear cells obtained from the same donor. In addition, this cell line showed a good transfection efficiency for other DNA sequences using classical transfection and selection techniques with a neomycin resistance gene (pKOneo). Selective microinjection of DNA into tumor precursor cells may prove useful for the study of the molecular mechanisms involved in breast carcinogenesis. The possible significance of the loss of 11p13-15 in malignant progression of breast cancer is discussed.     

Is verbal recognition memory really different in Huntington's and Alzheimer's disease.

Verbal recall and recognition were examined in Huntington's disease (HD) and Alzheimer's disease (AD) patients. Subgroups of HD and AD patients were matched for overall severity of dementia. Subjects were administered the Hopkins Verbal Learning Test, a list-learning task with three free-recall trials followed immediately by one yes/no recognition trial with semantically related and unrelated distractors. The matched AD and HD groups did not differ in the number of words recalled, although the HD patients showed slightly greater improvement over trials. Recognition performance was evaluated with measures of accuracy and response bias that are independent of each other. The matched groups did not differ in overall recognition accuracy, but the AD patients tended to have a more liberal ("yea-saying") response bias than did the HD patients. In addition, only the AD patients were differentially enticed to false-positive responding by semantically related distractors. The results suggest that the rule for making decisions when uncertain, rather than memory strength per se, distinguishes the recognition memory performance of AD and HD patients.     

Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study

Summary Magnetic resonance imaging and a comprehensive cognitive evaluation were carried out in a series of 29 patients with mild to moderate Huntington's disease (HD). A factor analysis of the neuropsychological test scores provided three factors: a memory/speed-of-processing factor, a frontal factor, and a response inhibition factor. The memory/speed factor correlated significantly with measures of caudate atrophy, frontal atrophy, and atrophy of the left (but not the right) sylvian cistern. There were no significant correlations between the frontal or response inhibition factors and measures of cortical or subcortical brain atrophy. Our findings confirm that subcortical atrophy is significantly correlated with specific cognitive deficits in HD, and demonstrate that cortical atrophy also has important association with the cognitive deficits of patients with HD.     

Quantification of doses to mediastinal lymph nodes in Hodgkin's disease.

Hodgkin's disease is highly curable today. Radiotherapy (RT) is the treatment of choice in the early stages. A mantle field is often used in the RT of Hodgkin's disease, and the technique and dosimetry are quite complex. We used computerized tomography (CT)-based dosimetry to determine doses delivered to different mediastinal nodes with the commonly used technique in Hodgkin's disease that was originally described by Kaplan. We used dose-volume histograms to determine doses to various groups of nodes in nine patients. Significant inhomogeneity (30%, 30%, 35%, 35%, 30%, 40%, 35%, 35%, and 30% in the nine patients) in dose distribution was found within the mediastinum. With the advent of 3-dimensional CT-based treatment planning, we are able to quantify such inhomogeneities. The question arises whether a homogeneous, lesser dose can achieve equal results. Average doses and "effective doses" were also calculated. The "effective doses" in eight patients (for a prescribed dose of 44 Gy) with a midline posterior spinal cord block added at 20 Gy were 37.3 Gy, 34.3 Gy, 36.0 Gy, 38.4 Gy, 35.8 Gy, 38.1 Gy, 36.7 Gy, and 36.7 Gy, respectively. A homogeneous dose equivalent to effective dose may achieve the same control as an inhomogeneous dose delivery. Prospective 3-D dosimetric studies are required to confirm this concept.