Naloxone and shuttlebox self-stimulation in the rat

Rats self timed electrical brain stimulation on and off periods in a shuttlebox. Electrodes for self-stimulation were located either in the lateral hypothalamic area (LHA) or the periaqueductal gray (PAG). Doses of the narcotic antagonist, naloxone, were administered intraperitoneally immediately prior to self-stimulation testing. Doses of 1.0, 5.0, 10.0 or 50.0 mg/kg failed to alter shuttlebox self-stimulation behavior. These results are inconsistent with one lever-press self-stimulation study employing PAG electrodes [3], but agree with other studies using LHA electrodes [9, 15, 21, 24]. Possible reasons for the discrepancy are suggested.     

Describing the severity of mottling in a community: a different approach

Dean's community mottling index, though a useful summary measure, suffers from the use of arbitrary scores and the inability to describe the frequency in each of the levels of mottling. An alternative statistical approach, based on the proportional odds model, is used here to describe the severity of mottling in a community. The use of this model is demonstrated on prevalence data collected on 16 Texas communities.     

Acute lower limb ischemia: Pathogenesis and management

Acute lower limb ischemia continues to be a problem both in diagnosis and management. The high mortality rate appears to be related to the metabolic consequences of ischemia, a function not only of time, but also of severity. The etiology of acute ischemia is reviewed along with the pathophysiological response. The management of the patient centers on diagnosis of cause and estimation of the severity of ischemia. Correction of metabolic disturbances and early restoration of flow is the preferred treatment, although there remains a place for late operative intervention in patients with less severe symptoms. Despite improved diagnostic and operative techniques, the thrombotic and metabolic changes that occur in the small vessels and muscular tissues appear to limit the success rate, with mortality rates remaining around 25%.     

Application of control theory to endocrine regulation and control

This paper considers some aspects of the application of control theory to endocrine regulation and control. Consideration is given to both the structural and functional aspects of various control concepts and ideas in this context. For single-input, single-output feedback control structures, emphasis is placed on loop gain and its importance in establishing the functional capability of such structures. Examples are given of both functional and nonfunctional feedback structures proposed by endocrinologists. For multi-input, multi-output structures, emphasis is placed on the concept of input and output decoupling, and the possible applicability of these concepts to hormonal control system interrelationships is illustrated. Finally, the possible application of optimal control theory to endocrine regulation and control is illustrated by means of a naive and highly simplified example involving control of the thyroid gland by the pituitary gland, and several surprising and interesting implications are shown to be implicit in the resulting control structure. Some of the material in this paper was developed while the author was an MHTP Fellow, Department of Psychiatry and Laboratory of Environmental Neurobiology, UCLA School of Medicine.     

Benefits of a multidisciplinary approach to breast care

The University of Michigan Breast Care Center (BCC) was established in 1985 to provide comprehensive, multidisciplinary diagnosis and treatment of benign and malignant breast disease. This work presents an overview of our experience in the BCC and assesses the clinical, academic, financial, and educational effectiveness of the program. A database was used to generate a list of all patients seen in the BCC between February 1, 1985 and December 31, 1991. Participating departments provided information regarding outpatient, inpatient, clinical and consultative activities, and referral patterns attributable to BCC endeavors. BCC educational and academic activities were reviewed and profiled. Clinical information was culled from the BCC database, hospital records, and the hospital tumor registry. The BCC has resulted in a fivefold increase in breast care related activity at the University of Michigan Medical Center. Over half of the patients treated in the BCC with primary operable breast cancer receive breast-conserving therapy. The BCC performs a unique educational function, providing the primary breast care experience for house staff as well as one third of the third year medical school class. The BCC supports over 20 clinical research protocols, and patient enrollment in clinical trials has increased dramatically since 1985. The BCC also provides support to basic science researchers receiving over 2.5 million dollars in peer reviewed direct cost support. These data suggest that a multidisciplinary approach to patient care as embodied by the BCC can be clinically, financially, and academically superior and productive. This model warrants further investigation not only in the field of breast care, but also in other clinical situations that require multidisciplinary input and therapy. © 1993 Wiley-Liss, Inc.     

Phase II evaluation of teniposide (VM-26) in metastatic breast carcinoma

The Southeastern Cancer Study Group performed a Phase II study of teniposide in previously treated patients with metastatic breast cancer. No responses were observed in 11 evaluable patients who received teniposide 60 mg/m² by IV infusion for five consecutive days every three weeks. Toxicity was primarily gastrointestinal and hematologic and was frequently severe. This study demonstrated no therapeutic activity for teniposide when given in this dose and schedule to patients with heavily pretreated metastatic breast cancer.     

Bioassay screening for toxicants in oil samples from the toxic-oil syndrome outbreak in Spain

A bioassay screening procedure was developed using an agar-plate inhibition assay and applied to a set of 32 oil samples obtained during investigations of the toxic-oil syndrome in Spain. After blind-decoding, it was noted that the assay had singled out the case-associated sample as the most toxic oil from the 32-sample set. Five other oil samples were also selected by the assay. Further evaluation showed that these case-associated, suspect case-associated, and miscellaneous oils had significantly more peroxidation than the controls, as indicated by the thiobarbituric acid assay. Products reactive with dinitrophenylhydrazine were present in greater amounts in the assay-selected oils, also indicating larger amounts of aldehydic and ketonic peroxidation products. A volatile peroxidation product, 4-hydroxy-2,3-nonenal (4-hydroxynonenal), was identified and was very toxic to the bioassay screen. The assay-selected oils had significantly greater amounts of this compound. Heating the toxic oils either removed or destroyed the toxic components as revealed by bioassay testing. The 4-hydroxynonenal and other unidentified toxic products were present in the assay-selected oils before heating and absent after heating. Toxic peroxidation products apparently caused the observed response in the assay-selected oils. These findings may indicate that peroxidation, or some type of free radical process, was associated with the toxicity of these oils to humans. The bioassay procedure should be applied to a larger set of epidemiologically documented oils to determine if this screening process can contribute to a better understanding of the toxic-oil syndrome.