Schedule-controlled brain self-stimulation: Has it utility for behavioral pharmacology?

We review evidence that schedule-controlled intracranial self-stimulation (ICSS) has properties in common with conventional reinforcements, such as food and water, but unlike the latter, animals will respond for ICSS for long periods of time at a near-constant rate. Schedule-controlled ICSS has proven to be more sensitive to drug-induced changes than has ICSS on a continuous reinforcement schedule, and it permits a more fine-grained analysis of the pattern of responding that results in the reinforcement. Evidence is accumulating that the schedule of ICSS itself leads to neurochemical changes in areas of the brain, such as the nucleus accumbens, in which reward processes occur. Results obtained from schedule-controlled ICSS would complement those obtained by drug self-administration studies which generally use intermittent reinforcement. A systematic examination of ICSS schedules at different brain sites would greatly facilitate our interpretation of drug effects and this would have utility for behavioral pharmacology.     

Human chronic kidney allograft rejection is accompanied by increased intraglomerular cathepsin B and L activity

Abstract The major reason for late graft losses is chronic rejection. Recently, a large number of studies have indicated that proteolytic enzymes play an important role as mediators of glomerular injury. The cysteine proteinases cathepsins B and L degrade structural matrix proteins such as type I collagen and laminin. We investigated intraglomerular protease activities in 12 patients after kidney graftectomy because of end-tage renal disease following chronic rejection. A group of 12 patients undergoing nephrectomy because of cancer served as controls using only non-involved parts of the kidney. The activities of cathepsins B and L in homogenates of isolated glomeruli were measured fluorometrically methylcoumarylamidc substrates and related to DNA content. In rejected kidney allografts we observed significantly enhanced intraglomerular cathepsin B activity and cathepsin B + L activity.     

Lifetime diagnoses in patients with somatoform disorders: Which came first?

Thirty inpatients with somatoform disorders were examined with the structured clinical interview SCID for psychiatric lifetime diagnosis. In the present diagnoses, we found a concordance of 63% for somatoform and affective disorders and the lifetime comorbidity of both disorders was 87%. Additionally, patients with somatoform disorders frequently had a history of other psychiatric disorders (for example, anxiety disorders, 40%). For 73% of patients with somatoform disorders and a history of affective disorders, the onset of the somatoform disorder was prior to the onset of another psychiatric disorder. The time interval between the onsets of somatoform disorders and affective disorders was greater than 1 year for most patients; for 46% of the patients with a history of both disorders, the time interval between the two disorders was more than 5 years. The course of illness for somatoform and affective disorders was quite different; while affective disorders tended to episodic periods with interim remissions, the somatoform disorders usually showed long, chronic courses (mean duration of the current somatoform disorder was 11.9 years). Finally, the Symptom Check List SCL-90R demonstrated good discrimination between patients with affective and anxiety disorders. However, the SCL-90R failed to discriminate patients with somatoform disorders from affective- and anxiety-disordered subjects. Therefore, the development of other psychometric scales is necessary for the evaluation of patients with somatoform disorders.     

Creating a professional practice environment on a shoestring

Did you ever think, “If we just had a little money we could…”? The current health care environment is wrought with financial stressors that can be overwhelming and take up most of our time. Such stress can limit the development of a professional practice environment if you let it. How do you not only survive but thrive in this financial climate?     

CO2 laser surgery of oral premalignant lesions

Experiences gained in the CO2 laser treatment of patients with oral dysplastic precancerous lesions are presented. Besides 7 lichens planus, 50 leukoplakias of all grades of dysplasia, and carcinoma in situ and one lentigo maligna were removed superficially with a defocused laser. Within the average follow-up period of 37 months, 22% local recurrences were observed. In comparison with conservative drug therapy, conventional surgical procedures, and cryosurgical therapy, the CO2 laser treatment of multicentric premalignant diseases of the oral mucosa can be recommended as an alternative therapy.     

Silent supraglottic carcinoma

In a review of 51 consecutive patients with previously untreated squamous cell carcinoma of the supraglottic larynx, five (9.8%) patients were found to have no mucosal abnormality on initial evaluation by both computed tomography (CT) and direct laryngoscopy. All five patients who manifested submucosal disease had at least one endoscopic procedure done with a biopsy negative for cancer before definitive diagnosis, resulting in an average delay from initial endoscopy to diagnosis of 19.8 weeks. These inapparent or "silent" neoplasms present unique problems in regard to establishing a diagnosis by routine biopsy techniques, even though CT reliably demonstrates their presence. Early diagnosis requires aggressive biopsy techniques based on CT findings.     

Immune reactions associated with silicone-based ventriculo-peritoneal shunt malfunctions in children

The implantation of ventriculo-peritoneal (VP) shunting systems is the most commonly performed neurological procedure in children with hydrocephalus. Although the overall complication risk is low, the cumulative risk of shunt failure is high and unfortunately results in a high prevalence of revision surgeries. In this study, we explored the concept that some pediatric patients may develop an immune response to either the proteins attached to the silicone implant surface or to the biomaterial itself, and that this reaction may contribute to VP shunt failure in some individuals. The data displays that the sterile shunt malfunction group had a higher rate of protein deposition and increased levels of autoantibodies to the extracted surface proteins as compared to individuals with functioning shunting systems. The precise nature of the shunt-bound proteins that serve as antigens in this experiment have not yet been determined. The data also indicated that some individuals develop antibodies to polymeric substances that cross-react with partially polymerized acrylamide. The detection of significant amounts of shunt-bound protein, antibody responses to these proteins and to polymeric substances suggest that an immunological response to these proteins may play a role in the mechanism behind sterile shunt malfunctions.