Reduced natural killer cell cytotoxicity in depression but not in schizophrenia.

A reduction of natural killer (NK) cell activity has been found in hospitalized patients with major depressive disorder. To examine whether a reduction of NK activity is found in other psychiatric patients or related to the nonspecific effects of hospitalization, NK cell cytotoxicity was compared in hospitalized depressed patients, schizophrenic inpatients, and two groups of controls separately age matched to each patient group. NK activity was significantly (p less than 0.01) lower in depressed inpatients than control subjects. However, in the hospitalized schizophrenic patients values of natural cytotoxicity did not differ from controls. These findings suggest that reduced NK cytotoxicity in depression is independent of the effects of hospitalization.     

Shoulder instability: impact of glenohumeral arthrotomography on treatment

We used arthrotomography to study the glenoid labrum in 114 patients. Sixty-nine of the patients had anatomic instability of the shoulder (including recurrent dislocation and subluxation of the shoulder), and 45 patients had functional instability of the shoulder (denoted by chronic pain, clicking of the joint, and the sensation that an unstable condition exists without the objective signs of it). Labral tears were revealed arthrotomographically in 86% of the patients with anatomic instability, while only 40% of the patients with functional instability had labral abnormalities, and these were primarily of minor severity. Fifty-six patients (44 of whom had anatomic instability; 12, functional instability) required surgery. The surgical findings were correlated with the arthrotomographic findings, and no false-positive results were revealed. However, arthrotomography demonstrated only part of the pathologic condition of two patients. These results confirm that there is a strong correlation between labral pathologic conditions and anatomic instability of the shoulder. Arthrotomographic studies have a great impact on the selection of therapy in cases of both anatomic and functional instability of the shoulder.     

Institution-wide program for impaired residents at a major teaching hospital

An institution-wide program for residents impaired by alcohol, other drugs, or emotional problems was established in 1983 at the Medical College of Wisconsin Affiliated Hospitals. The goal of the program was to help impaired house staff members to continue their training in a nonpunitive environment. An approach to reviewing allegations of impairment and a legal agreement between the hospital and the recovering resident were implemented. Because no residents were reported for impairment during its first two years, the program's emphasis was shifted from an investigative to an educational, assistive role. Major problems in carrying out the program have been the program's lack of authority to ensure cooperation by program directors and by impaired residents; a widespread unfamiliarity with intervention procedures despite efforts to inform residents, their spouses, faculty members, and administrators about the program; and misconceptions that the program is punitive. Further impediments are lack of a budget to provide educational activities, inadequate socializing between the faculty and the house staff that would enable faculty members to recognize early signs of impairment; and inadequate health insurance coverage for long-term treatment.     

Sensorimotor disinhibition in Parkinson's disease: effects of levodopa.

It has been known for some time that patients with Parkinson's disease (PD) have difficulty executing simultaneous motor acts, yet the pathophysiology underlying this impairment remains uncertain. We examined the possibility that these dual-task deficits stem from defective sensorimotor mechanisms producing interference between the motor programs underlying the two tasks. Patients with PD and normal control subjects were tested on their ability to maintain steady-state force with one hand while performing a force-reaction time task with the other hand. Although performance was worse on the dual-task than on the single-task condition for both subject groups, only the patients with PD demonstrated significant interference between the two tasks. The interference across tasks improved in 87% of the patients with PD when tested after treatment with carbidopa/levodopa (Sinemet). These findings support the contention that, in patients with PD, disturbances in the execution of simultaneous motor performance may be due to sensorimotor disinhibition.     

Antitumorale Wirkung von Interferonen und Interleukinen in Kombination mit Strahlentherapie

BACKGROUND: During the last 2 decades, cytokines such as interferons (IFN) have been used to modulate tumor response in radiotherapy. Initially, the focus was on antiviral and radiosensitizing effects of interferons but increasingly, the function of interferons and interleukins (IL) within the immune response to tumor cells is becoming important. METHOD: The cellular immune response toward tumor cells is reviewed. The role of cytokines in antigen presentation and activation of effector cells and their interactions with radiation are described. Preclinical strategies of the antitumor action of cytokines are presented and discussed based on the induction of IFN-gamma by IL-12. RESULTS: Recent advances in immunology have demonstrated the importance of local interactions between antigen-presenting cells (APC) and effector cells such as natural killer (NK) cells and T-lymphocytes for an effective immune reaction against tumors. Interferons stimulate such interactions, while IL-2 plays a central role in the activation of NK cells and T-lymphocytes. The interactions between APC and effector cells are suppressed by many tumors but can be stimulated by irradiation. Since systemic application of interferons is quite toxic, present strategies aim at local expression, e. g., the induction of IFN-gamma expression in Th1 cells by IL-12. CONCLUSION: The improved understanding of immunologic mechanisms has emphasized the role of the cytokine network in the interaction between tumor cells and effector cells such as NK cells and T-lymphocytes. This opens new possibilities for the application of cytokines as biological response modifiers, which may eventually help widening the therapeutic window in radiotherapy.     

The relationship between borderline personality disorder and anxiety disorders

Eleven "pure" borderlines, ten borderlines with depression, 16 "pure" depressives, and 31 normal subjects were compared on a number of standardized inventories of anxiety. While patient groups experienced more anxiety of all types than did normals, borderlines did not emerge as more anxious than other patient groups. Qualitative differences in the anxiety experienced by borderlines and nonborderlines are discussed.     

Differences among hospitals in Medicare patient mortality.

Using hospital discharge abstract data for fiscal year 1984 for all acute care hospitals treating Medicare patients (age greater than or equal to 65), we measured four mortality rates: inpatient deaths, deaths within 30 days after discharge, and deaths within two fixed periods following admission (30 days, and the 95th percentile length of stay for each condition). The metric of interest was the probability that a hospital would have as many deaths as it did (taking age, race, and sex into account). Differences among hospitals in inpatient death rates were large and significant (p less than .05) for 22 of 48 specific conditions studied and for all conditions together; among these 22 "high-variation" conditions, medical conditions accounted for far more deaths than did surgical conditions. We compared pairs of conditions in terms of hospital rankings by probability of observed numbers of inpatient deaths; we found relatively low correlations (Spearman correlation coefficients of 0.3 or lower) for most comparisons except between a few surgical conditions. When we compared different pairs of the four death measures on their rankings of hospitals by probabilities of the observed numbers of deaths, the correlations were moderate to high (Spearman correlation coefficients of 0.54 to 0.99). Hospitals with low probabilities of the number of observed deaths were not distributed randomly geographically; a small number of states had significantly more than their share of these hospitals (p less than .01). Information from hospital discharge abstract data is insufficient to determine the extent to which differences in severity of illness or quality of care account for this marked variability, so data on hospital death rates cannot now be used to draw inferences about quality of care. The magnitude of variability in death rates and the geographic clustering of facilities with low probabilities, however, both argue for further study of hospital death rates. These data may prove most useful as a screening mechanism to identify patterns of potentially poor quality of care. Careful choice of the mortality measure used is needed, however, to maximize the probability of identifying those hospitals, and only those hospitals, warranting more in-depth review.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.