Daily changes in presynaptic cholinergic activity of rat sympathetic superior cervical ganglion

The in vitro capacity of sympathetic superior cervical ganglia (SCG) to take up [³H]choline from the extracellular medium, to synthesize acetylcholine from [³H]choline, and to release [³H]acetylcholine in response to a high K⁺ concentration, were examined in rats throughout a 24-h cycle. Both the release of [³H]acetylcholine and the synthesis of [³H]acetylcholine from [³H]choline exhibited significant diurnal variations, showing maxima during the first half of the night. After these maxima, nocturnal acetylcholine release and synthesis decayed to daytime levels and remained low until the end of the night. [³H]Choline uptake by rat SCG did not vary significantly throughout a 24-h period. A 1.5-h exposure of rats to darkness at the 5th hour of light phase of the daily photoperiod did not change significantly any parameter studied. A 20-min, 5-Hz, electrical stimulation of the preganglionic trunk of SCG excised from rats at noon increased significantly subsequent K⁺-induced [³H]acetylcholine release but did not change [³H]acetylcholine synthesis. In decentralized SCG of rats subjected to a unilateral SCG decentralization and a contralateral sham-operation 7 days earlier, [³H]acetylcholine release and synthesis were highly reduced or abolished at the decentralized side, while [³H]choline uptake remained unaltered. The present results suggest that an activation of preganglionic rat SCG neurons takes place during the first half of the scotophase.     

Evaluation of the culture of safety: survey of clinicians and managers in an academic medical center

Background: Despite the emphasis on patient safety in health care, few organizations have evaluated the extent to which safety is a strategic priority or their culture supports patient safety. In response to the Institute of Medicine's report and to an organizational commitment to patient safety, we conducted a systematic assessment of safety at the Johns Hopkins Hospital (JHH) and, from this, developed a strategic plan to improve safety. The specific aims of this study were to evaluate the extent to which the culture supports patient safety at JHH and the extent to which safety is a strategic priority.

Methods: During July and August 2001 we implemented two surveys in disparate populations to assess patient safety. The Safety Climate Scale (SCS) was administered to a sample of physicians, nurses, pharmacists, and other ICU staff. SCS assesses perceptions of a strong and proactive organizational commitment to patient safety. The second survey instrument, called Strategies for Leadership (SLS), evaluated the extent to which safety was a strategic priority for the organization. This survey was administered to clinical and administrative leaders.

Results: We received 395 completed SCS surveys from 82% of the departments and 86% of the nursing units. Staff perceived that supervisors had a greater commitment to safety than senior leaders. Nurses had higher scores than physicians for perceptions of safety. Twenty three completed SLS surveys were received from 77% of the JHH Patient Safety Committee members and 50% of the JHH Management Committee members. Management Committee responses were more positive than Patient Safety Committee, indicating that management perceived safety efforts to be further developed. Strategic planning received the lowest scores from both committees.

Conclusions: We believe this is one of the first large scale efforts to measure institutional culture of safety and then design improvements in health care. The survey results suggest that strategic planning of patient safety needs enhancement. Several efforts to improve our culture of safety were initiated based on these results, which should lead to measurable improvements in patient safety.

     

Ciprofloxacin-induced renal insufficiency in cystic fibrosis.

Acute renal insufficiency is known to occur in patients who are taking ciprofloxacin, particularly the elderly. We report two young patients with cystic fibrosis who presented with acute renal insufficiency after 2-3 weeks of oral ciprofloxacin therapy. The incidence of this adverse effect in children and young adults who have cystic fibrosis is unknown. Multiple mechanisms for ciprofloxacin-induced nephrotoxicity have been proposed.     

Patterns of angiogenesis in neural transplant models: I. Autonomic tissue transplants

Functional vascular connections must form rapidly to prevent ischemic damage to grafted neural tissues. The temporal sequence by which transplant circulation is re-established provides information about the angiogenic capacity of either intact or damaged CNS blood vessels. This study compares the time course and mechanism of vascular reperfusion in allografts of superior cervical ganglia or adrenal medulla inserted either into the fourth ventricle or directly into the parietal cortex of perinatal rats. Tritiated thymidine was administered to recipients to determine angiogenic patterns at various postoperative time periods. After processing for light microscopic autoradiography, host and graft endothelial labelling indices were determined in order to establish the temporal sequence and location of vascular proliferation. Correlative electron microscopy depicted the morphological changes in transplant vasculature. Some recipients were prelabelled with 3H thymidine prior to transplantation to determine if host vessels invaded the grafts. Intraventricular graft vessels initially collapsed but sustained minimal ischemic damage and were completely reperfused by 24 hours postoperative. Adjacent intact host vessels attained peak 3H thymidine incorporation at 20 hours. Intrinsic graft vessels were radioactively labelled only after 48 hours. Intraparenchymal transplants surrounded by minimal trauma exhibited a similar temporal sequence of reperfusion and host endothelial proliferation. Intrinsic graft vessels in intraparenchymal grafts sustained more severe damage. With increased trauma, a concomitant delay in graft reperfusion time was observed. Grafts within prelabelled hosts rarely contained any labelled endothelium, indicating that anastomotic connections were made between original, intrinsic graft vessels and nearby host vascular sprouts. This study demonstrates that mature autonomic tissue stimulates the growth of adjacent host vessels when transplanted to undamaged brain surfaces. The anastomosis of nascent host vessels with pre-existing graft vessels is responsible for the rapid re-establishment of circulation within the transplants. A similar mechanism occurs within intraparenchymal grafts, although the rapidity of reperfusion appears to be predicated on the amount of trauma present at the graft site.     

Developmental Expression of Neuron-Specific Enolase Immunoreactivity and Cytochrome Oxidase Activity in Neocortical Transplants

The present study has examined certain metabolic markers in fetal neocortical tissue transplanted to the cortex, hippocampus, striatum, or ventricle. Particularly, the immunocytochemical expression of neuron-specific enolase (NSE) was studied in a series of host rats ranging between 10 days and 15 months postoperative. NSE is a major glycolytic pathway enzyme found in all neurons. The antibody to NSE is a very reliable marker for neuronal functional metabolic activity and developmental status and its onset has been shown to coincide with synaptic connections. In some grafts oxidative metabolic status was investigated using cytochrome oxidase (CO) histochemistry. In addition, the normal development of NSE expression in rat neocortex was also examined. In normal development, NSE was weakly expressed in fetal brain, but by 1-2 weeks postnatal the enzyme was strongly expressed in all neurons. Typical cortical laminar patterns were evident at 30 days with neurons in layer V and scattered interneurons the most strongly stained. In cortex-cortex transplants NSE expression was very weak; at 1-3 weeks postoperative, it was practically nonexistent; and at all later times only a minority of neurons had normal expression when compared to that in normal development even though by Nissl staining standards in adjacent sections they appeared "normal." Labeling indices ranged between 30 and 49%. Intraventricular grafts had consistently low NSE expression with labeling indices ranging between 18 and 46%. However, when the neocortical tissue was placed in other regions, neuronal NSE appeared only slightly below normal. CO histochemistry corroborated the NSE activity with regards to graft placement. Several possibilities that may account for reduced NSE profile in transplanted neurons include incomplete migration patterns, reduced synaptic connectivity, and potential ischemia causing lowered protein synthesis during reestablishment of vascular connections. If neuronal glycolysis is weakened, it is possible that neurotransmitter production or axonal transport are reduced. Since most energy capacity in brain is dependent on the glycolytic sequence for oxidative metabolism, reduced glycolytic capacity, as depicted by NSE expression, may suggest the presence of transplanted neurons that have adapted to their new environment with a relatively immature profile.     

The use of fenbendazole in the treatment of commercial turkeys infected with Ascaridia dissimilis

Birds on a commercial turkey Farm were treated with fenbendazole on two separate occasions. For each treatment, fenbendazole was administered in the feed for 3 days at 30 mg/kg. Mean Ascaridia dissimilis total counts in randomly selected birds were 14.4 and 33.0 prior to the first and second treatments, respectively, whilst post-treatment counts averaged only 0.1 and 0.3, respectively. Anthelmintic effectiveness as demonstrated by both treatments was >99.0%. No untoward effects were noted with either fenbendazole treatment. After fenbendazole withdrawal, routine treatments with piperazine dihydrochloride were commenced with no apparent anthelmintic effectiveness. Mean total nematode burdens rose to 153.9 with a high individual count of 451. The potential for severe ascaridiasis when effective anthelmintic intervention is precluded was demonstrated.     

Recurrent bacteriuria and primary biliary cirrhosis: ABO blood group, P1 blood group, and secretor status.

Patients with primary biliary cirrhosis have an abnormally high incidence of urinary tract infection (35%). Susceptibility to urinary infection and other infectious diseases has been linked with certain blood group antigens and secretor status. We have therefore studied these characteristics in patients with primary biliary cirrhosis. We were unable to show any abnormal distribution in blood groups or secretor status in patients with primary biliary cirrhosis (compared with a normal population) which might reflect their predisposition to urinary infection. The distribution of blood groups and secretor status in patients with primary biliary cirrhosis with a history of urinary infections was not significantly different from patients without such a history. Escherichia coli strains isolated from patients with primary biliary cirrhosis did not bind in any greater numbers to the uroepithelial cells of primary biliary cirrhosis patients than to the cells of a normal healthy control. We therefore conclude that blood group distribution, abnormal secretor status, and epithelial cell type are not important factors in the predisposition of primary biliary cirrhosis patients to urinary infections.