"The myth of mental illness:" continuing controversies and their implications for mental health professionals

Since the publication of "The Myth of Mental Illness" in 1960, there has been an ongoing debate about Thomas Szasz's ideas concerning mental illness. In this paper, Szasz's views are summarized, as are the views of Szasz's critics. Specifically, the following areas are addressed: Szasz's definition of disease, his notions regarding the unconscious and rationality, his beliefs regarding culpability, his proposed differences between psychiatry and other branches of medicine, the uses of the term "mental illness," and the possibility of implicating physical lesions in some mental illnesses. With this discussion as a backdrop, the importance of these issues to mental health practitioners is addressed.     

Outcome of Perthes'' disease in unselected patients after femoral varus osteotomy and splintage

PURPOSE: To study the incidence, cause, recovery time, and prevention of diplopia following subcutaneous injection of botulinum A toxin for the treatment of facial spasms. METHODS: Patients who experienced diplopia after botulinum A toxin injections had their deviations examined in detail. When the muscle that caused diplopia was identifiable, the injection closest to that muscle was omitted in the next treatment in an attempt to prevent diplopia. RESULTS: Of 250 patients receiving about 1500 sets of injections, 25 (1.7%) incidents of diplopia occurred in 10 patients. Excluding two patients who declined further treatment after having diplopia on their first botulinum A toxin treatment, seven of the remaining eight patients had multiple incidents of diplopia. The most common pattern of diplopia was "uncertain diagnosis." The most common identifiable cause of diplopia was paresis of the inferior oblique muscle. Omission of the injection into the central portion of the lower eyelids in the next treatment prevented recurrence of diplopia in only one of the four patients. No significant correlation between botulinum A toxin doses injected and times to recovery was noted. CONCLUSIONS: Diplopia following botulinum A toxin treatment is uncommon. Seven patients (3% of patients studied) had 22 episodes of diplopia (88% of episodes). When diplopia occurs, it tends to recur on reinjection, sometimes with a prolonged recovery time. This response may not be dose dependent. The extraocular muscles of some patients may be more susceptible to chemodenervation than others, or botulinum A toxin may diffuse to extraocular muscles more easily in some patients than in others.     

Cellular and molecular biomarkers indicate precocious in vitro senescence in fibroblasts from SAMP6 mice. Evidence supporting a murine model of premature senescence and osteopenia

A variety of short-lived mouse strains (SAMP strains) and control strains of less abbreviated life span (SAMR strains) have been proposed as murine models of accelerated senescence. Each SAMP strain, in addition to displaying "progeroid" traits of accelerated aging, exhibits a singular age-related pathology. The application of this animal model to the study of normal aging processes has been and remains controversial. Therefore, we have undertaken a study of dermal fibroblasts derived from the short-lived SAMP6 strain, which shows early-onset and progressive osteopenia. We have investigated cellular and molecular characteristics that are associated with in vitro aging of normal human fibroblasts, and which are exacerbated in fibroblasts from patients with Werner syndrome, a human model of premature senescence. We found that SAMP6 dermal fibroblasts, relative to SAMR1 and C57BL/6 controls, exhibit characteristics of premature or accelerated cellular senescence with regard to in vitro life span, initial growth rate, and patterns of gene expression.     

Hematopoietic malignancies demonstrate loss-of-function mutations of BAX

The BCL-2 gene family regulates the susceptibility to apoptotic cell death in many cell types during embryonic development and normal tissue homeostasis. Deregulated expression of anti-apoptotic BCL-2 can be a primary aberration that promotes malignancy and also confers resistance to chemotherapeutic agents. Recently, studies of Bax-deficient mice have indicated that the pro-apoptotic BAX molecule can function as a tumor suppressor. Consequently, we examined human hematopoietic malignancies and found that approximately 21% of lines possessed mutations in BAX, perhaps most commonly in the acute lymphoblastic leukemia subset. Approximately half were nucleotide insertions or deletions within a deoxyguanosine (G8) tract, resulting in a proximal frame shift and loss of immunodetectable BAX protein. Other BAX mutants bore single amino acid substitutions within BH1 or BH3 domains, demonstrated altered patterns of protein dimerization, and had lost death-promoting activity. Thus, mutations in the pro-apoptotic molecule BAX that confer resistance to apoptosis are also found in malignancies.     

Ethical care at the end of life

In treating dying patients, who by virtue of their physical and emotional situation are frail and vulnerable, physicians must meet a high standard of professional, ethical care. Such a standard is based upon a philosophy of care that recognizes the patients' inherent worth as human beings and their uniqueness as individuals. The ethical and virtuous physician will practice in accordance with the principles of biomedical ethics that form the foundations of thought and treatment approaches in this area and will seek to do the best for the patient and the family. "Doing the best" includes respecting autonomy through gentle truth-telling, helping the patient and family to set treatment goals, and providing for symptom control, continuing attentive care and accompaniment throughout the course of the illness. Total care includes physical, emotional and spiritual aspects, is sensitive to cultural values and is best provided by an interdisciplinary team. Practices of symptom control in routine care and in crisis situations, as well as the cessation and non-initiation of treatment, will have as their goals the relief and comfort of the patient. The ethical physician will not act with the intention of bringing about the death of the patient, whether by ordering medication in excess of that required for symptom control, administering a lethal injection or any other means.     

Sites important for PLCbeta2 activation by the G protein betagamma subunit map to the sides of the beta propeller structure

The betagamma subunits of the heterotrimeric GTP-binding proteins (G proteins) that couple heptahelical, plasma membrane-bound receptors to intracellular effector enzymes or ion channels directly regulate several types of effectors, including phospholipase Cbeta and adenylyl cyclase. The beta subunit is made up of two structurally different regions: an N-terminal alpha helix followed by a toroidal structure made up of 7 blades, each of which is a twisted beta sheet composed of four anti-parallel beta strands (Wall, M. A., Coleman, D. E., Lee, E., I?iguez-Lluhi, J. A., Posner, B. A., Gilman, A. G., and Sprang, S. R. (1995) Cell 83, 1047-1058; Lambright, D. G., Sondek, J., Bohm, A., Skiba, N. P., Hamm, H. E., and Sigler, P. B. (1996) Nature 379, 311-319). We have previously shown that sites for activation of PLCbeta2, PLCbeta3, and adenylyl cyclase II overlap on the "top" surface of the propeller, where Galpha also binds (Li, Y., Sternweis, P. M., Charnecki, S., Smith, T. F., Gilman, A. G., Neer, E. J., and Kozasa, T. (1998) J. Biol. Chem. 273, 16265-16272). The present study was undertaken to identify the regions on the side of the torus that might be important for effector interactions. We made mutations in each of the outer beta strands of the G protein beta1 propeller, as well as mutations in the loops that connect the outer strands to the adjacent beta strands. Our results suggest that activation of PLCbeta2 involves residues in the outer strands of blades 2, 6, and 7 of the propeller. We tested three of the mutations that most severely affected PLCbeta2 activity against two forms of adenylyl cyclase (ACI and ACII). Both inhibition of ACI and activation of ACII were unaffected by these mutations, suggesting that if ACI and ACII contact the outer strands, the sites of contact are different from those for PLCbeta2. We propose that distinct sets of contacts along the sides of the propeller will define the specificity of the interaction of betagamma with effectors.     

Hemophilia. A new approach to an old disease

The history of hemophilia diagnosis and therapy has been a turbulent one. We are coming full circle, back to the use of genetics as the main diagnostic tool for this disease. Therapeutically, the retroviruses that ravaged one generation of hemophiliac patients now may participate in the cure for the next generation. The hemophilia community hopes that the future of hemophilia care will follow a course guided by this modified quote from James Russell Lowell: "New times demand new measures, and men [and women]. As the world advances and in time outgrows the laws that in our fathers' [and mothers'] days were the best, doubtless after us some purer scheme will be shaped out by wiser man [and women] than we, made wiser by the steady growth of truth."