Cephaloridine nephrotoxicity in streptozotocin induced diabetic Fischer 344 (F344) rats

The purpose of this study was to determine if cephaloridine nephrotoxicity is attenuated in streptozotocin (STZ)-induced diabetic rats. Fischer 344 (F344) rats (205-250 g) were given a single injection (i.p.) of STZ (27-35 mg/kg) or citrate buffer. The nephrotoxicity of (750 mg/kg) cephaloridine (i.p.) was then compared with normoglycemic and 14-day diabetic rats. Increased blood urea nitrogen (BUN) levels as well as diminished renal cortical slice accumulation of tetraethylammonium (TEA) and lactate-stimulated p-aminohippurate (PAH) were measured (P less than 0.05) in normoglycemic rats 48 h after cephaloridine administration. Cephaloridine failed to alter BUN levels and organic ion accumulation in diabetic rats. Diabetes did not totally protect against cephaloridine toxicity since kidney weights were elevated in normoglycemic and diabetic rats 48 h after administration of 750 mg/kg cephaloridine. A series of experiments also measured BUN levels, kidney weight and renal cortical slice uptake of PAH and TEA 24, 48 and 72 h after (1500 mg/kg) cephaloridine administration. Cephaloridine increased (P less than 0.05) kidney wt and decreased PAH and TEA uptake (P less than 0.05) in the normoglycemic group at 24-72 h. No change in kidney wt, PAH or TEA uptake was observed in the diabetic rats. These data indicate diabetes reduces cephaloridine nephrotoxicity.     

The effects of cardiopulmonary bypass and cold cardioplegia on coronary flow velocity and the reactive hyperemic response in patients and dogs

In normal coronary arteries, reactive hyperemic responses to a 20-second occlusion, an index of coronary reserve, usually demonstrate a peak-to-resting flow velocity ratio of 4:1 or more. Most intraoperative studies that have assessed reactive hyperemic responses in bypassed vessels have reported peak-to-resting flow velocity ratios of 2:1 or less following a 20-second occlusion. These decreased reactive hyperemic responses could be due to coronary vasodilatation after cardiopulmonary bypass or to an inadequate physiological result of the surgical procedure. In 14 patients with angiographically normal coronary arteries, the peak-to-resting flow velocity ratio following a 20-second coronary occlusion decreased significantly (p less than 0.05) from 4.4 +/- 0.2 (mean +/- standard error) before bypass to 3.0 +/- 0.3 after bypass. In a similar dog model, the peak-to-resting flow velocity ratio decreased by 36 to 52% during the first hour following one hour of cardiopulmonary bypass and cardioplegia. During the same period, left ventricular perfusion increased 21 to 30%, mean arterial pressure and coronary vascular resistance decreased, and myocardial oxygen consumption was unchanged. In a second group of dogs studied for the effects of duration (200 to 240 minutes) of anesthesia and thoracotomy alone, peak-to-resting flow velocity ratio was significantly lower. These clinical and experimental studies suggest that major coronary vasodilatation occurs early following cardiopulmonary bypass and cold cardioplegia, and may contribute to the blunted coronary reactive hyperemic responses reported during this time. Consequently, an intraoperative peak-to-resting flow velocity ratio of 3:1 for bypassed coronary arteries may represent an excellent physiological result.     

Cinefluoroscopic evaluation of periprosthetic cardiac valve regurgitation

The results of cinefluoroscopic evaluation in 509 patients in whom there was no evidence of prosthetic mitral or aortic valve regurgitation were compared with those in 41 patients who had perivalvular aortic or mitral regurgitation. Rotational motion of the base ring of each prosthesis (base-ring tilt) was measured in at least two views. A base-ring tilt of 7 degrees or more for aortic prostheses or 11 degrees or more for mitral prostheses was associated with an increased incidence of significant perivalvular regurgitation. Likewise, in patients who had multiple studies, a change between studies in base-ring tilt of 4 degrees or more for aortic prostheses or 5 degrees or more for mitral prostheses was associated with significant perivalvular regurgitation. These data suggest that the presence of either an abnormal base-ring tilt or an abnormal increase in base-ring tilt is strong, supportive evidence of partial prosthetic valve dehiscence.     

Dual function nitroimidazoles less toxic than RSU 1069: selection of candidate drugs for clinical trial (RB 6145 and/or PD 130908.

Following the toxicity and synthetic difficulties encountered with the hypoxic cell radiosensitizer RSU 1069, efforts have focused on development of a superior analogue. Two compounds, RB 6145 and PD 130908, have emerged from this program which overcome the instability and synthetic problems associated with RSU 1069 while retaining favorable biological activity. Both agents show comparable radiosensitizing activity to RSU 1069 following oral or i.p. administration to mice bearing the KHT or RIF-1 tumors. Sensitizing efficiency is about 10 X greater than that observed for misonidazole or etanidazole. Toxicity toward hypoxic tumor cells in vivo is demonstrated by clamping tumors (for 60 min) following administration of PD 130908 or RB 6145. Both are effective hypoxic cytotoxins, but less potent than RSU 1069. Systemic toxicity is substantially reduced following oral drug administration. Further, doses achievable following fractionated drug treatments are sufficiently high to produce significant levels of radiosensitization.     

Mutated c-Ha-ras oncogene alters cytokeratin expression in the human breast epithelial cell line MCF-10A.

MCF-10A, a spontaneously immortalized human breast epithelial cell line, has been transformed by transfection with the mutated c-Ha-ras oncogene obtained from T24 carcinoma cells. The pattern of cytokeratin expression was studied in MCF-10A cells in comparison with plasmid transfected or MCF-10Aneo cells, normal ras proto oncogene transfected or MCF-10AneoN cells, and transformed or MCF-10AneoT cells. Cytokeratin expression was studied by western immunoblot of total cellular proteins separated by two-dimensional gel electrophoresis. Blots with cytokeratin specific AE1 and AE3 antibodies showed identical molecular weight species of cytokeratins in MCF-10A, MCF-10Aneo, MCF-10AneoN, and MCF-10AneoT cells; however, in MCF-10AneoT cells, the intensity of immunostaining and the number of immunoreactive phosphorylated polypeptides keratins 7, 8, 15, and 16 was decreased. It was concluded that c-Ha-ras oncogene-induced transformation alters quantitatively the cytokeratin pattern of human breast epithelial cells and that these changes could explain some of the morphologic alterations observed in c-Ha-ras transformed cells.     

Adjustment to spinal cord injury: stage theory revisited

To better understand adjustment following spinal cord injury (SCI), 106 subjects from two samples (N = 53 each) were administered the SCL-90-R, a symptom checklist, and the Multidimensional Health Locus of Control scales. Sample 1 subjects were admitted for rehabilitation during 1981 to 1982 and sample 2 subjects were admitted during 1984 to 1986. Sample 2 subjects entered rehabilitation programs more quickly after injury and reported more anxiety, phobic anxiety, and hostility than sample 1 subjects. Within each sample, there was no evidence for a relationship between age or time since injury and health beliefs or psychological distress. This study does not support stage theory for adjustment after catastrophic injury, but does suggest the importance of understanding the impact of social policy changes in adjustment following spinal cord injury.     

Drug information course for pharmacy staff development.

An interactive course in drug information skills developed for pharmacists at a not-for-profit, tertiary-care hospital is described. Faculty members from the area school of pharmacy developed, taught, and evaluated the program. Before the course was developed, pharmacy staff members were asked to rate their drug information skills; the pharmacists' responses indicated their belief that they were not proficient enough in the skills needed in daily practice. The course content and format were refined after 11 pharmacists completed a pilot program. A handbook was developed that contained objectives, session outlines, and literature for each of the six topics chosen for the course. Although the handbook was the primary teaching aid, wall charts and computer demonstrations were also used. Sessions were structured for the needs of adult students by using a small-group discussion format that emphasized the practical relevance of the information and encouraged participants to share personal experiences. Each session was offered on two separate days to facilitate attendance. Those who completed the course received credit for 12 contact hours of continuing education. Of 16 pharmacists enrolled in the course, 11 completed it. An interactive course in drug information skills, developed to meet the needs of hospital pharmacists, was well accepted because it incorporated personal experiences, small-group activities, and flexible scheduling.     

Corrosion potential variation of aged dental amalgam restorations over time.

OBJECTIVE: The corrosion potential of a dental amalgam restoration is generally determined using a single measurement, even though environmental factors and abrasion can continuously alter the surface state and reactivity of this alloy. It was, therefore, the purpose of this study to determine the maximum variability of the corrosion potential of aged dental amalgam restorations, for 28 days. METHODS: The corrosion potentials of 148 aged dental amalgam restorations in 12 human subjects were measured at t = 0 and 4 h, and 4, 7, 14, 21 and 28 days. Measurements were made with a high impedance voltmeter and a Ag/AgCl micro-reference electrode. The subjects were instructed not to alter their usual eating and oral hygiene routines. RESULTS: Corrosion potential changes occurred throughout the 28 days. They were both positive and negative for the same restoration, and were sometimes very large. Only 4 h after the initial measurement, the absolute value of the corrosion potential changes ranged between 18 and 287 mV for 50% of the restorations. The largest maximum absolute corrosion potential change for each subject's restorations ranged between 85 and 329 mV. Statistical analysis showed that the overall mean maximum absolute corrosion potential change for the subjects' restorations was 74 mV. SIGNIFICANCE: It was shown that the corrosion potential of aged dental amalgam restorations varies substantially over time, and that a single measurement is not representative of short- or long-term electrochemical behavior. This finding has implications regarding the corrosion rate of dental amalgam restorations, particularly those that are part of a galvanic couple.