Antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors

BACKGROUND: Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles.They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders. OBJECTIVE: To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. PATIENTS AND METHODS: Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects. RESULTS: Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups. CONCLUSIONS: These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.     

The Massachusetts Behavioral Health Program Year 5: Transition to a New Managed Care Organization

Year 5 of the Massachusetts Behavioral Health Program was a transition to management by a new private managed care organization. Fifty-eight providers interviewed for an ongoing panel survey reported slightly lower levels of quality, access, utilization, and length of stay than a year earlier. Relationships with providers and advocates improved after an initial difficult period, while consumer and family involvement at all levels remained low. The greatest changes in managed care appeared to take place during the initial transition from fee-for-service care, but intractable problems continue, and full participation of stakeholders seems difficult to achieve.     

Visual perceptions of head-fixed and trunk-fixed anterior/posterior axes

The purpose of the present experiment was to determine the preferred visual straight ahead or anterior/posterior (a/p) axis at the perceptual level. The ability of 12 neurologically normal, young adult subjects to position a rod parallel to the head and trunk a/p axes while viewing eccentrically located visual targets were studied under six conditions: 1. fixed — subjects stood erect with the head aligned to the trunk and viewed a central target while visually aligning a hand-held rod to the head and trunk a/p axis. 2. eyes — subjects moved only their eyes to view eccentric targets and aligned the rod to the head and trunk a/p axis. 3. head-trunk — subjects viewed the eccentric targets by rotating the head about a vertical axis and aligned the rod to the trunk a/p axis. 4. head-head — subjects viewed the targets as in 3 and positioned the rod parallel to the head a/p axis. 5. trunk-head — subjects viewed the targets by rotating the trunk and head as a unit about the vertical axis and aligned the rod parallel to the head a/p axis (note that the head and trunk a/p axes were misaligned by the experimenter prior to target viewing). 6. trunk-trunk — subjects viewed targets as in 5 and positioned the rod parallel to the trunk a/p axis. Subjects performed 25–35 consecutive trials within each condition. Perceptual errors were similar for aligning the rod to the trunk and head a/p axes; however, moving the trunk produced much larger constant and variable perceptual errors than moving the head. In a second experiment, four subjects controlled the position of a lighted rod held by a robot arm in complete darkness. They were instructed to align the rod to either the head or trunk a/p axis under conditions similar to the fixed, head-trunk, and head-head tasks described above. Perceptual errors were much larger when aligning the rod to the head a/p axis than to trunk a/p axis when the head was moved. This shows that the trunk a/p axis is clearly preferred at the perceptual level when visual background cues are not present.These data strongly suggest that the visual coordinate system uses a trunk-fixed a/p axis to define the subjective straight-ahead direction and right/left position of a target. Implications of these findings for sensorimotor transformations in control of upper limb movements to visual targets are discussed.     

Malignant lymphoma, small lymphocytic type: a clinicopathologic study of 84 cases with suggested criteria for intermediate lymphocytic lymphoma.

Clinical and histopathologic findings were reviewed in 84 cases of malignant lymphoma of the small (well differentiated) lymphocytic type. The slides were studied without clinical information, and the following morphologic features were evaluated: pattern of growth, number of large lymphocytes, mitotic rate, degree of capsular involvement, presence of plasma cells and/or plasmacytoid lymphocytes, and presence of residual germinal centers. Subsequently, clinical information was obtained. The minimum follow-up period on living patients was 5 years. The patients were divided into 3 clinical categories: 1) monoclonal gammopathy (MG)-11 cases, 2) chronic lymphocytic leukemia (CLL) without MG-56 cases, and 3) those without MG or CLL at the time of lymph node biopsy-17 cases. The criterion for CLL was an initial absolute lymphocyte count less than 4000/mm3. Four of the patients with MG also had CLL, and 6 of those in the third group later developed CLL, from 1 to 61 months after lymph node biopsy. Generalized lymphadenopathy was the usual presentation in all 3 groups, and bone marrow examination was positive in all but 1 of the 49 cases, representing all 3 groups, in which it was performed. Median survival for the 84 patients was 51 months. The only clinical parameters which showed a significant association with poorer survival were age above 60 and anemia (Hb. conc. less than 11.0). There was no significant relationship between morphologic characteristics and clinical categories other than the association of plasmacytoid cells with MG in 6 cases. A mitotic rate of 30 or more mitoses per 20 high power fields (HPF), found in 5 cases with at least 1 in each clinical category, showed a highly significant association with decreased survival (p = .01). Variations in mitotic rate between 0 and 29 mitoses per 20 HPF and other morphologic parameters did not show a significant relationship with prognosis. It was concluded that malignant lymphoma of the small lymphocytic type is a definite clinicopathologic entity which may or may not exhibit MG or CLL, and it is proposed that the term "intermediate lymphocytic lymphoma" be applied only to those cases showing histopathologic characteristics of small lymphocytic lymphoma and a mitotic rate of 30 or more mitoses per 20 HPF.     

A six year longitudinal study of the occupational consequences of drinking over "safe limits" of alcohol.

Although much research has focused on the psychological, social, and economic consequences of heavy problem drinking, there has been far less attention paid to the consequences of "moderate" drinking. This study used a unique opportunity to carry out a six year follow up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to details on sickness absence, labour turnover, and promotion. It has provided evidence that even moderate alcohol consumption in the working population is associated with social costs for the employer and the employee, including substantial sickness absence, and lack of promotion in men, although the increase in labour turnover was not statistically significant. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on performance and labour turnover.     

Functional Impairment and Cognition in Bipolar Disorder

Bipolar disorder is a common, chronic and severe mental disorder, affecting approximately 2% of the adult population. Bipolar disorder causes substantial psychosocial morbidity that frequently affects the patient's marriage, children, occupation, and other aspects of the patient's life. Few studies have examined the functional impairment in patients with affective illness. Earlier outcome studies of mania reported favorable long-term outcomes. However, modern outcome studies have found that a majority of bipolar patients evidence high rates of functional impairment. These low reports of functional recovery rates are particularly surprising. The basis for such limited functional recovery is not entirely clear. Factors associated with functional dysfunction include presence of inter-episode symptoms, neuroleptic treatment, lower social economic class, and lower premorbid function. Cognitive dysfunction, a symptom domain of schizophrenia, has been identified as an important measure of outcome in the treatment of schizophrenia. Recently, there has been some suggestion that there may be impaired neuropsychological performance in euthymic patients with recurring mood disorders. Whether impaired neuropsychological performance in associated with the functional impairment in bipolar patients who have achieved syndromal recovery is an intriguing question. The literature on functional impairment and cognition in bipolar disorder is reviewed.     

In vivo degradation of tungsten embolisation coils

It has been suggested that tungsten embolisation coils in intracranial aneurysms may dissolve in situ. These coils are also used, in much larger quantities, for the occlusion of larger vessels outside the cranium. This study was performed to investigate whether tungsten embolisation coils may become degraded in vivo and to examine whether this is radiographically evident on medium-term follow-up. 10 patients who had undergone aortic stent-graft repair of an abdominal aortic aneurysm (8 male and 2 female, mean age 69.7 years) and 10 age- and sex-matched controls were studied. The study group had also received an average of 64 cm of tungsten coil either to prevent or to treat an endoleak. Whole blood, serum and urine tungsten levels were assayed. Immediate post-operative and follow-up abdominal radiographs were reviewed by two consultant vascular radiologists to detect visible changes in the coils. Whole blood, serum and urine levels of tungsten were highly and significantly elevated (p < 0.001) in the study group compared with the controls. No radiographic changes in the coils were seen at an average of 16.7 months. In conclusion, tungsten embolisation coils dissolve in humans but radiographic changes are not apparent on medium-term follow-up. The clinical significance of these findings is uncertain but long-term follow-up is needed.     

Functional impact of breast cancer by age at diagnosis.

PURPOSE: To explore changes in physical and psychosocial function before and after breast cancer by age at diagnosis. PATIENTS AND METHODS: A total of 122,969 women from the Nurses' Health Study (NHS) and NHS 2, ages 29 to 71 years, who responded to pre- and postfunctional status assessments were included; 1,082 women were diagnosed with breast cancer between 1992 and 1997. Functional status was measured using the Medical Outcomes Study Short Form 36 (SF-36). Mean change in health-related quality of life (HRQoL) scores was computed across categories representing the combination of incident breast cancer (yes or no) and age at diagnosis (< or = 40, 41 to 64, or 65+ years). RESULTS: Compared with women < or = 40 years without breast cancer, women with breast cancer experienced significant functional declines. Young (age < or = 40) women who developed breast cancer experienced the largest relative declines in HRQoL (as compared with middle-aged and elderly women) in multiple domains including physical roles (-18.8 v -11.5 and -7.5 points, respectively), bodily pain (-9.0 v -2.7 and -2.7 points), social functioning (-11.3 v -4.3 and -4.4 points) and mental health (-3.1 v 0.0 and +0.4 points). Much of the decline in HRQoL among elderly (age > or = 65) women with breast cancer was age related. CONCLUSION: Young women may fare worse than middle-aged or elderly women in both physical and psychosocial dimensions after breast cancer diagnosis. The needs of women facing breast cancer may be better understood within a life stage framework.