Depletion in amygdaloid 5-hydroxytryptamine concentration and changes in social and aggressive behaviour

Summary 5, 7-Dihydroxytryptamine (10 and 20g) was microinjected bilaterally into the amygdaloid complex of rats and resulted in 55% and 80% depletion in 5-hydroxytryptamine concentration, respectively. The lesioned animals exhibited fewer dominance behaviours and submitted more often to an intruder into their home-cages than did the vehicle-injected controls. The lesioned rats were also more submissive than were the controls when they were intruding into another rat's territory. Only the higher dose of toxin altered social investigatory behaviour when this was measured in an arena in which neither rat had established territory. The lesioned rats displayed less social interaction and had reduced levels of motor activity. The results are compared with those of other studies in which there has been regional or general depletion of brain 5-hydroxytryptamine concentration.     

Flexible fiberoptic sigmoidoscopy—The monroe clinic experience

Analysis of 5000 consecutive flexible fiberoptic sigmoidoscopies form the basis of this report. It is concluded that this method of examination of the distal large bowel is not only safe and comfortable for the patient but is a more appropriate examination than the rigid proctosigmoidoscopy because of the significant increase in pathologic material found. This examination has proven practical and acceptable in a multispecialty clinic setting and has completely replaced rigid proctosigmoidoscopy. Flexible sigmoidoscopy is now the standard "routine" examination of the rectum and distal colon. The rationale for this conclusion is presented in this timely report.     

In vitro studies of intragastric digestion

Following consumption of a meal, 99% of the large food particles are emptied only after intragastric fragmentation has reduced their diameter to less than 2 mm. Anin vitro model was constructed to evaluate some of the factors which may play a role in the process of intragastric digestion. Gastric mixing of food was simulated in a silicone rubber tube (ID 19 mm) placed in a peristaltic pump. Peristaltic waves progressed upwards along the tube at a frequency of 0, 1, or 3/min, reducing the internal diameter of the tube to 5 mm. Cooked chicken liver particles (2–2.8 mm in diameter) were placed in the tube with one of the following: (1) 150 mM NaCl, (2) 150 mM HCl with or without pepsin, or (3) phosphate buffer at pH 7, 5.4, or 2.6 + pepsin. After 30 min, the extent of particle reduction and of solubilization of proteins were determined and expressed as percent of the initial liver weight. The diameter of liver particles was reduced to a greater extent in NaCl than in pH 7 buffer or acid solutions with or without pepsin. In contrast, the amount of proteins solubilized was enhanced two- to threefold by acid pepsin solutions compared to NaCl or pH 7 phosphate. The presentin vitro studies suggest that changes in motor and/or secretory activity of the stomach significantly modify intragastric digestion.     

Fournier's gangrene: A general surgery problem

Fournier's gangrene is a specific form of synergistic gangrene involving the scrotum and perineum. The disease may follow a variety of clinical conditions or occur without an apparent precipitating cause. It is associated with severe systemic toxicity and a significant mortality rate, and it demands prompt recognition and urgent, aggressive surgical intervention. Its treatment calls on the full armamentarium of the general surgeon. Preoperative resuscitation is often required. Operative debridement can be extensive, involving the buttocks and on occasion the upper thighs and abdominal wall. Postoperative management consists of wound care with eventual grafting or flap rotations. Colostomy may be required. Three cases illustrating the salient features of this disease are presented, together with a review of the literature.     

Radiographic techniques to evaluate paintings

Radiographic techniques may be helpful in evaluation of the condition of paintings for their restoration, preservation, and occasionally to determine their authenticity. On the basis of experience with several of these procedures, the utility of each method is described in reference to specific "diagnoses" regarding paintings. Radiographic techniques have several advantages over other methods; they are nondestructive, they may be used to survey the entire painting, and they are subject to quantitative and serial analysis.     

Reading, Demographic, Social and Psychological Factors Related to Pre-adolescent Smoking and Non-smoking Behaviors and Attitudes

The purpose of this study was to examine reading, demographic, social and psychological factors related to pre-adolescent smoking and non-smoking behaviors and attitudes. The school-home humanistic education program was implemented in a large, urban public school system. It stressed responsible decision-making, increased self-esteem and the inter-relationships among the acquisition of knowledge of the consequences of smoking, personal feelings, family relationships and behavior. The results showed that family involvement was necessary to affect smoking attitudes and behaviors. Of all the variables studied, reading had a most pervasive relationship. Peer influence and self-esteem also were related to smoking knowledge, smoking attitude, future smoking intentions and the "purchase" of cigarettes. Two of several conclusions drawn from the results are: 1. Family involvement is necessary to affect attitudes and behaviors. 2. Health education research that does not investigate the relationship between program outcomes and reading achievement may be misleading.     

Hybrid Pharmacokinetic Models to Describe Anti-HIV Nucleoside Brain Disposition Following Parent and Prodrug Administration in Mice

Brain delivery of active anti-HIV compounds is important for successful treatment of the AIDS patient. As an initial step in predicting human brain drug concentrations, hybrid pharmacokinetic models were developed to characterize the disposition of anti-HIV nucleosides following parent and prodrug administrations in mice. Mouse data were obtained following intravenous administration of 3-azido-2,3-dideoxyuridine (AZddU or AZDU), 3-azido-3-deoxythymidine (AZT), and their dihydropyridine prodrugs (AZddU-DHP and AZT-DHP). Exponential equations were fitted to the serum concentration–time data for each species, including the pyridinium ion moieties, and subsequently used in differential mass balance equations describing the brain dynamics of each compound. Model parameters for the mass balance equations were estimated by various techniques, including the utilization of in vitro data. In general, model-predicted brain concentrations agreed with the observed data. Similar data in larger animals will permit scale-up of the current model to predict human brain drug concentrations.     

Polyamine involvement in the secretion and action of TGF-α in hormone sensitive human breast cancer cells in culture

These experiments were designed to test polyamine (PA)* involvement in the secretion and action of transforming growth factor (TGF-) in hormone responsive MCF-7 breast cancer cells in liquid culture. At the same time, we evaluated the influence of culture conditions (with serum vs. serum depleted) and subclonality of MCF-7 cells on PA involvement in estrogen (E₂) and TGF- stimulated cell proliferation. Despite inducing a profound suppression of cellular PA levels and inhibiting basal and E₂-stimulated growth, administration of the PA synthesis inhibitor -difluoromethylornithine (DFMO) did not influence either basal or E₂-induced TGF- secretion. In the same experiments, on the other hand, addition of DFMO completely blocked the growth stimulatory effect of exogenous TGF-. However, when the culture conditions were changed to serum-free medium, TGF- and E₂-induced cell proliferation was affected modestly or not at all by DFMO administration, despite similar suppression of cellular ornithine decarboxylase (ODC) activity and PA levels. In addition, different clones of MCF-7 cells differed in their sensitivity to the antiproliferative effect of DFMO as well as in basal levels of ODC activity and PA. We conclude that PAs are not involved in basal or E₂-stimulated TGF- secretion in MCF-7 breast cancer cells. On the other hand, PAs do seem to be important mediators of TGF- and E₂-induced breast cancer cell proliferation, though the degree of such involvement appears to be influenced by serum factors and clonal variability of MCF-7 cells.     

Phase I and pharmacologic evaluation of intraperitoneal 5-fluoro-2′-deoxyuridine

Summary Intraperitoneal (i.p.) 5-fluoro-2-deoxyuridine (Floxuridine, FUdR, FdUrd) was evaluated in a phase I study at a starting level of 500 mg given on 1 day in 2 I 1.5% dialysate. Escalations within patients were allowed every other cycle. A total of 23 patients (age, 32–78 years) received 108 treatment courses. Local tolerance at all dose levels was excellent, with no cases of drug-related peritonitis being observed. Nausea and vomiting increased in severity in relation to dose and was universal at >3,000 mg ×3 days. One patient each developed grade 1 mucositis as well as diarrhea at a dose of 3,000 mg×3 days and leukopenia and thrombocytopenia at 5,000 mg×3 days. Peritoneal fluid (PF) and plasma (PL) FdUrd profiles were monitored by an HPLC method in 13 subjects, with 7 being studied serially at 2–4 increment doses for up to 6 h. Profiles that exhibited apparent linear pharmacokinetics gave PF drug levels 2–4 logs higher than the PL counterparts, with the latter essentially declining in parallel to the former, indicating that the disposition of FdUrd from the peritoneal compartment is rate-determining. The mean terminal half-life for PF FdUrd was found to be 115 min and mean peritoneal clearance was 25 ml/min. The vast differences in drug levels and AUC found between the PF and the PL profiles suggests a high systemic clearance of FdUrd, which was confirmed in two patients receiving 2 g FdUrd by short i.v. infusion. A disproportionate increase in the plasma FdUrd levels and the corresponding AUC values was found with increasing dose, suggesting a disproportionate increase in the systemic partitioning of FdUrd when doses were escalated within a patient. Substantial levels of peritoneal 5-fluorouracil (FUra) were also detected in most of the subjects. Thus, FdUrd was found to have several desirable properties for i.p. administration: (1) a 2- to 4-log pharmacologic advantage, (2) the absence of local toxicities, and (3) a favorable antitumor spectrum and some evidence of antitumor effects in this phase I and pharmacology study. A 3,000-mg dose given in 2 l 1.5% dialysate for 3 consecutive days exhibited antitumor activity and produced no systemic toxicity except nausea and vomiting, which was controlled by antiemetics. This dose schedule is therefore recommended for phase II trials directed against small-volume disease in the peritoneal cavity, such as may be found in some stages of ovarian and gastrointestinal cancers. In addition, it is suitable for further exploration as a part of regimens including systemic therapy or drugs that modulate the action of fluoropyrimidines.Supported in part by Cancer Center Core Grant CA 14089, by ROI CA 50 412, by an ACS Institutional Grant (IN21Z, to C. R.) and by the Italian-American Foundation award (to N. C.)Deceased