Editorial: Structured abstracts.
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Journal Article↗
Biomedical subjects
D Lowe
Publications and source records attributed to D Lowe.
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Education, Medical↗
Evaluation of a competitive NMDA antagonist (D-CPPene) in feline focal cerebral ischemia.
The effects of a competitive, N-methyl-D-aspartate (NMDA) receptor antagonist, D(-)E-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylic acid (D-CPPene), on the volume of ischemic brain damage was assessed by quantitative histological study in 35 chloralose-anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery and the animals were killed by transcardiac perfusion fixation 6 hours later. Pretreatment with D-CPPene (1.5, 4.5, or 15 mg/kg, administered intravenously 15 minutes prior to occlusion, with subsequent drug infusions to maintain a plateau in the plasma drug concentrations) effected dose-dependent reductions in the volume of ischemic brain damage. At the highest dose studied (15 mg/kg, plus an infusion of 170 micrograms/kg/min), D-CPPene reduced the volume of ischemic damage in the cerebral cortex by more than 75% compared to vehicle-treated control animals. The plasma concentration of D-CPPene, which is associated with a half maximal reduction in the volume of ischemic damage, was estimated to be 24 micrograms/ml during the initial 120 minutes after the middle cerebral artery occlusion. Treatment with D-CPPene (15 mg/kg, plus an infusion of 170 micrograms/kg/min) initiated 1 hour after occlusion reduced the volume of ischemic brain damage in the cerebral cortex by 30%, but this response did not achieve statistical significance. Precise definition of dose dependency for the anti-ischemic effects of NMDA antagonists and the therapeutic time window are influenced greatly by brain pharmacokinetics of the agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The influence of aging and attentional demands on recovery from postural instability.
It is well known that the risk of a debilitating injury from a fall is much higher for elderly than for young individuals. In addition, it is well documented that healthy elderly subjects exhibit increased postural sway during normal stance tasks. In the present experiment, we explored the notion that control of minor postural instability in elderly subjects is attention demanding. Postural sway of eight elderly (mean age = 70.0 years) and eight young (mean age = 20.0 years) subjects was measured under two different secondary demands during stable and mildly unstable upright stance. There were two types of work loads. Either a cognitive (math task) or motor (hand-squeeze) task was performed during the second segment of a 50-second standing trial. The effect of these work loads on mean velocity, range, and variability of range of center of foot pressure was measured during the destabilizing activity of arm swinging and subsequent recovery period. Following seven seconds of 1 Hz arm-swinging activity, elderly subjects showed a marked increase in recovery time to normal stance when concurrently performing an arithmetic task. This result suggests that recovery from a posturally destabilizing activity, involving proprioceptive and vestibular information, places increased attentional demands on the postural support system of the elderly.
Accidental Falls↗
Time-management study of trauma resuscitation.
A prospective time-management analysis of trauma resuscitation (TR) of 431 patients arriving at a university trauma center documents timing and organization. Severity of injury, patient age, and potential airway injury were significant factors increasing the duration of TR up to a certain time (36 minutes). Moderately injured patients required less time (under 25 minutes). Patients needing emergent operations spent a minimal amount of time (20 minutes) in TR. Potential injuries involving the airway or cervical spine, or shock, added minutes. A review of the timing and organization of TR suggests the need for improvement in airway assessment and management. Patients with certain mechanisms of injury and elderly patients with blunt injuries required additional time in TR. With surgery faculty supervision and senior resident attendance, the month of resident experience had no effect on TR times. A timely and organized TR is critical to trauma care. TR times should be documented for quality assurance and ongoing review.
Adolescent↗
Focal cerebral ischemia in the cat: pretreatment with a competitive NMDA receptor antagonist, D-CPP-ene.
The effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-CPP-ene; SDZ EAA 494) upon ischemic brain damage have been examined in anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of the middle cerebral artery (MCA) and the animals were killed 6 h later. The amount of early ischemic brain damage was assessed in coronal sections at 16 predetermined stereotaxic planes. Pretreatment with D-CPP-ene (15 mg/kg i.v. followed by continuous infusion at 0.17 mg/kg/min until death), 15 min prior to MCA occlusion, significantly reduced the volume of ischemic brain damage (from 20.6 +/- 9.9% of the cerebral hemisphere in vehicle-treated cats to 7.2 +/- 4.4% in drug-treated cats; p less than 0.01). The competitive NMDA receptor antagonist D-CPP-ene is as effective as noncompetitive NMDA antagonists in reducing the amount of ischemic brain damage in this model of focal cerebral ischemia in a gyrencephalic species.
Animals↗
Characterization of factors that direct transcription of rat ribosomal DNA.
The protein components that direct and activate accurate transcription by rat RNA polymerase I were studied in extracts of Novikoff hepatoma ascites cells. A minimum of at least two components, besides RNA polymerase I, that are necessary for efficient utilization of templates were identified. The first factor, rat SL-1, is required for species-specific recognition of the rat RNA polymerase I promoter and may be sufficient to direct transcription by pure RNA polymerase I. Rat SL-1 directed the transcription of templates deleted to -31, the 5' boundary of the core promoter element (+1 being the transcription initiation site). The second factor, rUBF, increased the efficiency of template utilization. Transcription of deletion mutants indicated that the 5' boundary of the domain required for rUBF lay between -137 and -127. Experiments using block substitution mutants confirmed and extended these observations. Transcription experiments using those mutants demonstrated that two regions within the upstream promoter element were required for optimal levels of transcription in vitro. The first region was centered on nucleotides -129 and -124. The 5' boundary of the second domain mapped to between nucleotides -106 and -101. DNase footprint experiments using highly purified rUBF indicated that rUBF bound between -130 and -50. However, mutation of nucleotides -129 and -124 did not affect the rUBF footprint. These results indicate that basal levels of transcription by RNA polymerase I may require only SL-1 and the core promoter element. However, higher transcription levels are mediated by additional interactions of rUBF, and possibly SL-1, bound to distal promoter elements.
Animals↗
Focal ischemic damage is reduced by CPP-ene studies in two animal models.
We have studied a new high-affinity competitive N-methyl-D-aspartate antagonist, D-CPP-ene (SDZ-EAA 494), in two models of focal cerebral ischemia. In the cat middle cerebral artery occlusion model (6 hours' survival), pretreatment with D-CPP-ene reduced infarct size by 64% (15 mg/kg dose) and 60% (4.5 mg/kg dose). There was no reduction in infarct size at a dose of 1.5 mg/kg. Treatment 1 hour after the occlusion reduced infarct size slightly, but not significantly. In a new model of subdural hematoma in the rat, the zone of cortical ischemic damage beneath the blood clot was reduced by 54% with D-CPP-ene pretreatment. Neuroprotective efficacy in a gyrencephalic species comparable to that of noncompetitive antagonists thus can be achieved with this agent. These experiments also indicate that competitive N-methyl-D-aspartate antagonists may be clinically useful after traumatic intracranial hematomas.
Animals↗
Quality of life following liver transplantation: a preliminary report.
Although the quality of life attained after heart transplantation has been assessed, there is no equivalent information for recipients of liver grafts in this country. In this paper we report a cross-sectional survey of 81 adult patients in the Cambridge/King's College Hospital joint programme using the Nottingham Health Profile which is a validated measurement of the quality of life. The results show the quality of life to be high, and broadly similar to the levels expected in the general population. The data suggest an increase in the problems related to physical mobility (two-fold) and a reduction in problems of emotional reaction (a halving).
Adult↗
Recovery after subarachnoid haemorrhage.
OBJECTIVE: To determine the implications of subarachnoid haemorrhage for quality of life and aftercare. DESIGN: Prospective follow up study of patients surviving subarachnoid haemorrhage over one year (at discharge, three months, and one year) by examination of cognitive functions (a test battery) and changes in everyday life (semistructured interview). SETTING: Regional neurosurgical unit at a tertiary referral centre. PATIENTS: 100 Patients with subarachnoid haemorrhage; 17 were lost during the study because of ineligibility (further surgery, previous head injury, relevant psychiatric history, and cultural differences), loss of contact, and non-compliance; a further 13 patients who developed a neurological deficit were considered separately. MAIN OUTCOME MEASURE: Performance on cognitive test battery and reported changes in quality of life. RESULTS: At discharge patients with and without neurological deficit scored below established norms with most tests, but by three months the difference had resolved in patients without deficit. Reduced quality of life attributable to subarachnoid haemorrhage at one year mainly included less energy (seven patients), adverse emotional changes (five), early retirement, affected social life, and domestic tension (three each). None reported reduced capacity for work. CONCLUSIONS: Patients surviving subarachnoid haemorrhage without neurological symptoms have a good prognosis and should be encouraged to return to a normal lifestyle within about three months.
Adult↗
The role of bacterial infection of the maxillary sinus in nasal polyps.
Fifty-two adult patients with nasal polyps were studied. All patients had preoperative sinus radiographs which were coded on the degree of mucosal thickening and these were compared with the results of irrigation of the maxillary sinuses. All irrigations were sent for culture and microscopy for pus cells. Pus cells and bacteria were found in only 16 of 104 wash-outs. It was concluded that the disease results in stasis of secretions and secondary maxillary sinusitis.
Bacterial Infections↗
Cognitive outcome and quality of life one year after subarachnoid haemorrhage.
In this prospective study, 100 patients with subarachnoid haemorrhage (SAH) were assessed at discharge, 3 months, and 1 year using modern methods of neuropsychology to examine cognitive status and semistructured interviews to assess changes in personality and quality of life. A control group of 50 patients suffering myocardial infarction were also assessed at discharge and 1 year. Results of cognitive testing in the SAH group were unremarkable and compared well with the control group. Similarly, there was no evidence of a consequent reduction in the quality of life in the majority of the SAH patients. These results lead us to conclude that where the medical and surgical course of SAH is uncomplicated, patients recover with no permanent or significant reduction in their intellectual ability of life status. Possible reasons for the difference between these results and those of other studies are discussed.
Adult↗
Applying a theoretic framework for reducing medication errors in intensive care units.
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Competency-Based Education↗
The effects of different fixations on the distribution and numbers of mast cells in patients with nasal polyps.
Mast cells in rats have been categorized into mucosal and connective tissue mast cells by properties which include their fixation characteristics and their distribution in tissues. There are a number of factors which make this classification unsatisfactory including the variability of fixation, intensity of background staining and the application of animal studies to man. Seasonal allergic reactions in the nose of man occur both in the surface metachromatic cells and in those within the epithelium; the latter are presumed to be mucosal mast cells. The aim of this study was to look at the distribution and the fixation characteristics of mast cells in inferior turbinates and nasal polyps. Both techniques show that cells are more abundant in the submucosa and the fact that Carnoy's fixative shows them better and this may be due to the lack of intensity in the background staining. There is no evidence that mast cells are more frequent in the epithelium. These findings would suggest the nasal polyps are not an allergic disease.
Acetates↗
Controlled study of nimodipine in aneurysm patients treated early after subarachnoid hemorrhage.
We enrolled 75 consecutive patients admitted with subarachnoid hemorrhages in a randomized, double-blind, placebo-controlled trial to determine the effect of early intervention with nimodipine on outcome and cerebral blood flow. The cardioprotective effect of nimodipine was assessed by measuring the electrocardiographic changes over the first 3 days of drug treatment. There was a mild lowering of the mean cerebral blood flow in the nimodipine-treated group over the 21-day period. Analysis of the continuous electrocardiographic traces showed no difference between the nimodipine and placebo groups in the frequency or type of abnormality detected. At 3 months, 4 of the 38 patients receiving nimodipine had died, compared with 10 of the 37 placebo-receiving patients. Of the 50 eligible patients who had a proven cerebral aneurysm, 1 patient (4%) on nimodipine died compared with 6 (24%) receiving placebo (0.01 less than P less than 0.05, chi 2 test; approximate 95% confidence interval for mortality difference, 0.4% to 39.6%). We conclude that nimodipine does not increase the cerebral blood flow or protect the heart after a subarachnoid hemorrhage. There were no side effects from nimodipine. The trend toward improved outcome should be verified in a larger series of patients.
Adolescent↗
Does atenolol improve physical and psychological function after coronary artery bypass surgery: a controlled study.
A double-blind prospective randomized trial of atenolol (100 mg once daily) was carried out on 88 patients (78 men) awaiting coronary artery bypass graft surgery. Standardized ratings of both psychiatric morbidity and functional capacity were made before, 3 months (n = 82) and 12 months (n = 81) after surgery. One year after surgery men in the atenolol group had a significantly shorter treadmill exercise time than those on placebo (7.21 +/- 0.28 min vs 8.32 +/- 0.40 min; p less than 0.05), but the frequency of reported anginal attacks during the year was similar in both drug groups. Improvement in functional capacity (measured in exercise time) in the 71 men following surgery was related to both physical and psychological variables assessed before the operation. Men with more severe occlusive disease, lower neuroticism and higher extraversion scores pre-operatively showed greater percentage improvement in exercise time after surgery. Women had significantly levels of psychiatric morbidity and shorter treadmill exercise time than men both before and after surgery. Of the psychiatric and psychological variables, only ratings of Type A behaviour fell significantly in the atenolol group (170.9 +/- 5.3 vs 163.0 +/- 5.2; p less than 0.05). This change, which is probably not clinically important, occurred independently of any reduction in either overall psychiatric morbidity score or ratings of somatic symptoms mediated by beta-adrenergic receptors. The atenolol group reported more side-effects of both psychological and physical symptoms than the placebo group. We do not recommend the routine use of atenolol after bypass graft surgery. Our findings failed to support the suggestion that Type A characteristics may reflect an underlying sympathetic nervous system reactivity.
Angina Pectoris↗
The effects of a gonadotropin-releasing hormone agonist on testicular histology.
We have described the histologic changes in the testes of men treated with buserelin for prostatic cancer. If these changes are reversible, then the agonist analogues, together with testosterone replacement therapy, could be used safely for male contraception. If the changes are irreversible, then boys with central precocious puberty treated with such compounds would be of normal height, but sterile.
Aged↗
Early intervention with nimodipine in subarachnoid haemorrhage.
Seventy-five consecutive patients with subarachnoid haemorrhage (SAH) were entered into a randomized, double-blind, placebo-controlled trial prior to angiography in order to determine the effect of early intervention with nimodipine on blood pressure (BP), cerebral blood flow (CBF), and clinical outcome. Of these patients, 50 fulfilled the criteria for the final analysis (i.e. SAH due to cerebral aneurysm and receiving 21 days of treatment). There was no difference between the BP recordings of the two treatment groups, but mean CBF decreased slightly in the nimodipine group over the 21-day treatment period. At three months, one patient on nimodipine and six patients receiving placebo had died (P = 0.049, Fisher's exact test), but no significant difference was observed between the two groups, when the 'intent to treat' group of 75 patients was considered. We conclude that nimodipine does not increase CBF or alter BP following SAH, but an improved clinical outcome is evident at three months for patients with SAH due to cerebral aneurysm who had been treated with nimodipine. There were no side-effects due to nimodipine.
Adolescent↗