Occupational stress in neurosurgery: an exploratory study.

Occupational stress in nursing has been a popular topic for investigation. In particular, comparisons between practice areas such as the intensive care unit (ICU) and medical-surgical unit have attempted to identify what factors are stressful, and whether some nursing environments are more stressful than others. Such studies have led to inconclusive findings. While many practice areas have been studied, the neurosurgical ICU and neuromedical/neurosurgical units have largely been overlooked. Using interviews, this exploratory study examined aspects of nursing perceived as stressful by staff members working in ICU and medical-surgical units in a neuroscience center. Findings suggested that patient care, communication, workload, management and supervision, organizational and personal circumstances are major sources of stress. These findings are in keeping with studies of stress conducted in national and international non-neurosurgical nursing practice areas.     

The immediate consequences of middle cerebral artery occlusion on GABA synthesis in mouse cortex and cerebellum.

The effect on gamma-aminobutyric acid (GABA) synthesis of focal ischaemia in the right cortex of the mouse was investigated by performing a right middle cerebral artery (MCA) occlusion. Synthesis of GABA was determined by measurement of the rate of GABA accumulation in tissue following injection of amino oxyacetic acid (AOAA; 30 mg/kg, i.p.). Five min following the MCA occlusion, the rate of GABA synthesis in the right (ischaemic) cortex was decreased by approximately 70% compared to either the left cortex or the right cortex of untreated controls. The basal GABA concentration was however unaffected. Four hours after the occlusion the rate of GABA synthesis was similar in the right and left cortex. The rate of GABA accumulation in the cerebellum was unchanged at both times after the right MCA occlusion compared with untreated control mice. The data suggest that there is a rapid but short lasting decrease in GABA synthesis following an ischaemic insult and it is suggested that this might be associated with the EEG spiking activity that occurs at this time.     

Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus reactivation and infection post-allogeneic hematopoietic stem cell transplant continue to cause morbidity and mortality. Current pharmacologic therapies are limited by side effects. Adoptive transfer of ex vivo generated cytomegalovirus-specific T cells has the potential to restore immunity, prevent cytomegalovirus, and circumvent the need for pharmacologic therapies. We have generated donor-derived cytomegalovirus-specific cytotoxic T cells using dendritic cells pulsed with the HLA-A2 restricted nonapeptide NLVPMVATV (NLV) derived from the cytomegalovirus-pp65 protein. These cytotoxic T cells have been given prophylactically to 9 recipients aged 4 to 65 years on or after day 28 post-allogeneic hematopoietic stem cell transplant. Only 2 of 9 recipients received T cell depletion in vivo or in vitro. There were no immediate adverse reactions to the infusions. During 97-798 days of follow-up, 2 recipients developed cytomegalovirus reactivation; neither developed cytomegalovirus disease or required pharmacotherapy. Three recipients developed acute graft versus host disease after infusion. Two recipients died, 1 from thrombotic thrombocytopenia purpura secondary to cyclosporine, 1 from complications of graft versus host disease. A transient increase in numbers of cytomegalovirus-specific T cells demonstrated by NLV-tetramer binding was seen in 6 recipients. Prophylactic adoptive transfer of NLV-specific T cells is safe and may be effective in preventing cytomegalovirus reactivation.     

Septic Revision Total Knee Arthroplasty Is Associated With Significantly Higher Mortality Than Aseptic Revisions: Long-Term Single-Center Study (1254 Patients)

BackgroundThe aim of this study is to examine the differences in long-term mortality rates between septic and aseptic revision total knee arthroplasty (rTKA) in a single specialist center over 17-year period.MethodsRetrospective consecutive study of all patients who underwent rTKA at our tertiary center between 2003 and 2019 was carried out. Revisions were classified as septic or aseptic. We identified patients’ age, gender, American Society of Anesthesiologists grade, and body mass index. The primary outcome measure was all-cause mortality at 5 years, 10 years, and over the whole study period of 17 years. Death was identified through both local hospital electronic databases and linked data from the National Joint Registry/NHS Personal Demographic Service. Kaplan-Meier survival curves were used to estimate time to death.ResultsIn total, 1298 consecutive knee revisions were performed on 1254 patients (44 bilateral revisions) with 985 aseptic revisions in 945 patients (75.4%) and 313 septic revisions in 309 patients (24.6%). Average age was 70.6 years (range 27-95) with 720 females (57.4%). Septic revisions had higher mortality rates; patients’ survivorship for septic vs aseptic revisions was 77.6% vs 89.5% at 5 years, 68.7% vs 80.2% at 10 years, and 66.1% vs 75.0% at 17 years; these differences were all statistically significant (P < .0001). The unadjusted 10-year risk ratio of death after septic revision was 1.59 (95% confidence interval 1.29-1.96) compared to aseptic revisions.ConclusionrTKA performed for infection is associated with significantly higher long-term mortality at all time points compared with aseptic revision surgery.Level of EvidenceLevel IV.     

A comparative study in rats of the in vitro and in vivo pharmacology of the acetylcholinesterase inhibitors tacrine, donepezil and NXX-066

The in vitro and in vivo effects of the novel acetylcholinesterase inhibitors donepezil and NXX-066 have been compared to tacrine. Using purified acetylcholinesterase from electric eel both tacrine and donepezil were shown to be reversible mixed type inhibitors, binding to a similar site on the enzyme. In contrast, NXX-066 was an irreversible non-competitive inhibitor. All three compounds were potent inhibitors of rat brain acetylcholinesterase (IC50 [nM]; tacrine: 125 +/- 23; NXX-066: 148 +/- 15; donepezil: 33 +/- 12). Tacrine was also a potent butyrylcholinesterase inhibitor. Donepezil and tacrine displaced [3H]pirenzepine binding in rat brain homogenates (IC50 values [microM]; tacrine: 0.7; donepezil: 0.5) but NXX-066 was around 80 times less potent at this M1-muscarinic site. Studies of carbachol stimulated increases in [Ca2+]i in neuroblastoma cells demonstrated that both donepezil and tacrine were M1 antagonists. Ligand binding suggested little activity of likely pharmacological significance with any of the drugs at other neurotransmitter sites. Intraperitoneal administration of the compounds to rats produced dose dependent increases in salivation and tremor (ED50 [micromol/kg]; tacrine: 15, NXX-066: 35, donepezil: 6) with NXX-066 having the most sustained effect on tremor. Following oral administration, NXX-066 had the slowest onset but the greatest duration of action. The relative potency also changed, tacrine having low potency (ED50 [micromol/kg]; tacrine: 200, NXX-066: 30, donepezil: 50). Salivation was severe only in tacrine treated animals. Using in vivo microdialysis in cerebral cortex, both NXX-066 and tacrine were found to produce a marked (at least 30-fold) increase in extracellular acetylcholine which remained elevated for more than 2 h after tacrine and 4 h after NXX-066.     

Safety and tolerability of zalcitabine (ddC) in patients with AIDS or advanced AIDS-related complex in the European expanded access programme

This international expanded access programme was initiated to provide zalcitabine (o 75 mg three times daily) to patients with AIDS or advanced ARC who had failed, were no longer able to tolerate or were ineligible to receive zidovudine (ZDV). Data are available from 517 patients. No unexpected adverse events occurred during the study with 13.2% of patients discontinuing treatment due to drug-related adverse events. Peripheral neuropathy (PN) was the most common adverse event reported. This was considered to be at least possibly related to zalcitabine in 12.2% of patients, with only 2.3% of patients withdrawing from the study due to zalcitabine-associated PN. Patients with a baseline diagnosis of AIDS and a CD4 count 相似文献   

Perinatal changes in bombesin-stimulated muscle contraction in rabbit stomach and colon

Bombesin and its mammalian homologue, gastrin-releasing peptide, stimulate smooth muscle contraction and may promote the growth of gastrointestinal tissues. Isometric contraction of strips from circular muscle of the gastric fundus and longitudinal muscle of the distal colon were used to compare changes in the response to bombesin in newborn and weanling rabbits. There was an age-related qualitative change in gastric muscle from biphasic contractions including phasic and tonic components in the newborn to phasic contractions alone in the weanling. The colon contractions were tonic at both ages. In both tissues there was an age-related fivefold increase in stress in response to maximally effective concentrations of bethanechol (P less than 0.05). In contrast, in the stomach age-related decreases in the response to maximally effective concentrations of bombesin were observed, from 2930 +/- 179 mN/cm2 (98% of the maximal response to bethanechol) in the newborn to 565 +/- 81 mN/cm2 (4% of the maximal response to bethanechol) in the weanling (P less than 0.005). In the colon, a twofold increase in response to bombesin was observed, from 446 +/- 59 mN/cm2 (82% of the response to bethanechol) in the newborn to 862 +/- 11 mN/cm2 (29% of the response to bethanechol) in the weanling (P less than 0.05). No age-related changes were observed in the potency of bombesin in either tissue. Neither atropine nor tetrodotoxin altered the contractions in either tissue, suggesting that bombesin interacted directly with myocytes. There was three times as much bombesinlike immunoreactivity in the stomach compared with the colon, but no age-related changes in either tissue. In summary, by the age of weanling the stomach lost the tonic component of contraction and 80% of the efficacy of bombesin-stimulated phasic contraction that had been present in the newborn. The loss of efficacy, absolute in the stomach and relative to bethanechol in the colon, suggest that bombesin may be most important in stimulating motility in the neonatal period.     

Colonic motility and transit in health and ulcerative colitis

Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.     

Role of cholecystokinin in the gastrocolonic response to a fat meal

The fat component of the meal is the major stimulant of the gastrocolonic response. The aim of this study was to characterize the mechanism of the gastrocolonic response after eating fat in healthy human volunteers. A bipolar clip electrode recorded spike activity (SP) from the distal colon. An immediate increase in colonic spike activity occurred after eating a fat meal (18.0 +/- 3.0 SP/30 min) (p less than 0.02). Spike activity remained elevated for 90 min after eating the fat meal (18.6 +/- 2.7 SP/30 min) (p less than 0.01). The intravenous infusion of naloxone or atropine inhibited the fat-induced increase in colonic motility. Cholecystokinin is a candidate mediator of the fat-stimulated gastrocolonic response. The intravenous infusion of the octapeptide of cholecystokinin (20 ng/kg . h) stimulated an increase in distal colonic spike activity (16.0 +/- 3.7 SP/30 min) (p less than 0.025). Intravenous atropine did not affect stimulation of colonic motility by the octapeptide of cholecystokinin. Continuous infusion of naloxone, however, did inhibit stimulation of colonic spike activity by the octapeptide of cholecystokinin. There was no cross-reactivity between opiate or muscarinic receptors. These data suggest (a) fat stimulation of the gastro-colonic response required a muscarinic and opiate receptor, and (b) octapeptide of cholecystokinin can stimulate colonic motility, but it is not the major mediator of the gastrocolonic response.