Search PubMedSearch

Biomedical subjects

J Christie

Publications and source records attributed to J Christie.

At least 19 recordsLinked to original sources

Acute trauma alters morphine clearance.

Trauma is accompanied by changes in liver perfusion and acute phase proteins. Such changes have the potential to alter drug metabolism. There are few studies describing drug disposition in acute trauma. We determined the pharmacokinetics of an intermediate extraction drug, morphine, in trauma patients. Nine patients with an Injury Severity Score (ISS) > or = 16 were studied within 48 hours of trauma. Morphine 5 mg was given intravenously and serial blood and urine samples were drawn to derive pharmacokinetic parameters. Alpha acid glycoprotein (AAG) levels were determined. Total morphine clearance (CL) and volume of distribution (Vss) were decreased compared to established literature values. Area under the curve (AUC) and terminal half-life (T 1/2 alpha) were increased. AAG levels were higher than reference range. Elimination half-life was increased. The decrease we observed in Vss may be attributed to increased binding of morphine by AAG, which is increased after trauma as in our patients. Decreased clearance and increased half-life of an intermediate extraction drug may be explained by increased protein binding, decreased liver blood flow, and reduced hepatocellular function. Decreased clearance of the magnitude observed in these patients could result in drug accumulation. Better understanding of the effects of trauma on the pharmacokinetics of low, high, and intermediate extraction drugs will prevent excessive or suboptimal drug dosing.

Acute Disease

Do radionuclide and echocardiographic techniques give a universal cut off value for left ventricular ejection fraction that can be used to select patients for treatment with ACE inhibitors after myocardial infarction?

OBJECTIVE: To determine whether echocardiography and radionuclide angiography give comparable results when the left ventricular ejection fraction is measured early after myocardial infarction and thus whether, irrespective of the method used, a single value for the ejection fraction could be used as a guide for starting treatment with an angiotensin converting enzyme inhibitor. DESIGN: Prospective comparison of measurement of left ventricular ejection fraction by echocardiography and radionuclide angiography. SETTING: Coronary care units of two university teaching hospitals in Glasgow. PATIENTS: 99 patients studied within 36 hours of acute myocardial infarction. OUTCOME MEASURES: Left ventricular ejection fraction assessed by echocardiography and radionuclide angiography. RESULTS: 70 (77%) of the 99 patients had ejection fraction measured by both echocardiographic and radionuclide techniques, 30 in centre 1 and 40 in centre 2. In centre 1 the mean difference (SD) in ejection fraction (radionuclide angiography--echocardiography) was -8 (10%); 95% CI -12 to -4%. In centre 2 the mean difference was -14 (11%); 95% CI -17 to -11%. If patients had been treated with an ACE inhibitor on the basis of a radionuclide ejection fraction of < 40% then 93% in centre 1 (28 of 30) and 98% in centre 2 (39 of 40) would have been treated. This compares with 63% (19 of 30) and 50% (20 of 40), respectively if echocardiography had been used as a guide. CONCLUSION: Measurement of ejection fraction is highly dependent on the method used and it is therefore impossible to quote a universally applicable figure for left ventricular ejection fraction below which an ACE inhibitor should be used after myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors

Familiarity and attention: does what we know affect what we notice?

Previous work on the object and word superiority effects has demonstrated that activation from stored representations can facilitate identification of items in a visual display. We predicted that activation of this sort might exogenously attract visual attention toward items that have stored representations. To test this prediction, we presented a familiar (word) and an unfamiliar (nonword) item simultaneously at unpredictable locations, and after varying delays, moved one of the stimuli. In accord with our prediction, at the shortest intervals subjects were more efficient at discriminating motion of the familiar item. Control data demonstrated that this advantage was due to a competitive interaction and not to the familiarity of the items per se.

Adolescent

Absence of neuropathic pelvic pain and favorable psychological profile in the surgical selection of patients with disabling interstitial cystitis.

PURPOSE: We evaluated the results among patients with disabling interstitial cystitis treated by cystectomy, urethrectomy and creation of a continent colonic urinary reservoir (the Florida pouch). The value of psychological evaluation and pain localization techniques, as well as the use of a team approach in the evaluation of these patients were assessed. MATERIALS AND METHODS: The 20 women and 2 men who underwent surgery for disabling interstitial cystitis ranged from 31 to 75 years old (mean age 48). The duration of symptoms ranged from 2 to 14 years (mean 7). All patients had undergone multiple prior therapies, including vesical hydrodistension, instillations, laser treatments, and use of tranquilizers and a variety of pain medications. Patients underwent a clinical, cystoscopic (with bladder biopsies) and urodynamic evaluation as well as examination by a gynecologist with expertise in vaginal ultrasonography. The last 5 patients underwent psychological evaluation and pain localization techniques. RESULTS: Among the clinical parameters, the presence of a small capacity bladder with the patient under anesthesia (less than 400 cc) was associated with the best surgical results. Among 11 patients evaluated only clinically success was achieved in 64%, while all 5 (100%) who also underwent pain localization techniques and psychological evaluation had a successful outcome postoperatively. The overall surgical success rate in the 22 patients was 73%. Two patients undergoing psychological evaluation and pain localization techniques were not considered to be surgical candidates. Among 7 surgical failures 4 patients underwent postoperative psychological evaluation and pain localization techniques, and they would not have been considered candidates for surgery with the new parameters. CONCLUSIONS: A team approach is essential in the evaluation of these patients. Following the initial selection of patients who had a small bladder capacity while under anesthesia, psychological evaluation and pain localizing techniques may assist surgeons in selecting those who would benefit from a radical operation.

Adult

Tibial fractures with bone loss treated by primary reamed intramedullary nailing.

We reviewed the results of the treatment of 30 tibial fractures with minor to severe bone loss in 29 patients by early soft-tissue and bony debridement followed by primary locked intramedullary nailing. Subsequent definitive closure was obtained within the first 48 hours usually with a soft-tissue flap, and followed by bone-grafting procedures which were delayed for six to eight weeks after the primary surgery. The time to fracture union and the eventual functional outcome were related to the severity and extent of bone loss. Twenty-nine fractures were soundly united at a mean of 53.4 weeks, with delayed amputation in only one patient. Poor functional outcome and the occurrence of complications were usually due to a departure from the standard protocol for primary management. We conclude that the protocol produces satisfactory results in the management of these difficult fractures, and that intramedullary nailing offers considerable practical advantages over other methods of primary bone stabilisation.

Activities of Daily Living

Hip fractures in adults younger than 50 years of age. Epidemiology and results.

A review of the records of 3147 patients with hip fractures admitted to the authors' institution during a 5-year period revealed that 95 (3%) patients were aged 50 years or less at the time of fracture. Of patients between the ages of 20 and 40 years, hip fracture most commonly occurred in men after high-energy injuries. These injuries commonly occurred in the subtrochanteric and basicervical regions, or as a vertical transcervical fracture. In contrast, most patients between 40 and 50 years of age were medically frail and sustained osteoporotic-type fractures during simple falls. A treatment protocol of early reduction followed by internal fixation was evaluated in 75 nonpathologic fractures. At a mean of 25 months, fracture union with a good or satisfactory functional outcome was found in 57 (76%) patients, and 5 (7%) patients died of unrelated medical problems. Complications of primary treatment developed in 16 (21%) patients, but only 13 (17%) revision procedures were required. A satisfactory functional outcome was found in 10 patients who had uncomplicated revision surgery, but there were poor functional results in the 3 who required tertiary surgery. Despite the previously reported poor results of treatment of hip fracture in young adults, these results demonstrate that satisfactory results can be achieved with early, accurate fracture reduction followed by rigid internal fixation.

Adult

Exchange intramedullary nailing. Its use in aseptic tibial nonunion.

Exchange nailing for failure of union after primary intramedullary nailing of the tibia is widely used but the indications and effectiveness have not been reported in detail. We have reviewed 33 cases of uninfected nonunion of the tibia treated by exchange nailing. This technique was successful without open bone grafting in all closed fractures and in open fractures of Gustilo types I, II and IIIa. The requirement for open bone grafting was reduced in type-IIIb fractures, but exchange nailing failed in type-IIIb fractures with significant bone loss. For these we recommend early open bone grafting. The most common complication was wound infection, seen more often than after primary nailing. We discuss our protocol for the use and timing of exchange nailing of all grades and types of tibial fracture.

Adolescent

Transcardiac echocardiography during invasive intramedullary procedures.

We performed transoesophageal echocardiography in 111 operations (110 patients) which included medullary reaming for fresh fractures of the femur and tibia, pathological lesions of the femur, and hemiarthroplasty of the hip. Embolic events of varying intensity were seen in 97 procedures and measured pulmonary responses correlated with the severity of embolic phenomena. Twenty-four out of the 25 severe embolic responses occurred while reaming pathological lesions or during cemented hemiarthroplasty of the hip and, overall, pathological lesions produced the most severe responses. Paradoxical embolisation occurred in four patients, all with pathological lesions of the femur (21%); two died. In 12 patients large coagulative masses became trapped in the heart. Extensive pulmonary thromboembolism with reamed bone and immature clot was found at post-mortem in two patients; there was severe systemic embolisation of fat and marrow in one who had a patent foramen ovale and widespread mild systemic fat embolisation in the other without associated foraminal defect. Sequential analysis of blood from the right atrium in five patients showed considerable activation of clotting cascades during reaming.

Aged

Medullary lavage reduces embolic phenomena and cardiopulmonary changes during cemented hemiarthroplasty.

We randomised 24 patients before they had a cemented hemiarthroplasty for hip fracture to receive either thorough or minimal saline lavage of the femoral canal. We then determined the effect in each group on the thromboembolic and cardiopulmonary responses to the pressurised insertion of cement, using transoesophageal echocardiography to show the echogenic embolic response. We found a statistically significant reduction in both the duration of the response and the number of large emboli in patients who had had thorough lavage as compared with the control group with minimal lavage. There was also less disturbance of pulmonary function, as assessed by the change in end-tidal CO2 levels and oxygen saturation, in patients who had thorough lavage. Three patients had a significant fall in blood pressure during cement insertion; all had only minimal lavage. We consider that thorough lavage should be an essential part of the preparation of the proximal femur before cement insertion.

Aged

Cardiorespiratory and symptomatic variables during maximal and submaximal exercise in men with stable effort angina: a comparison of atenolol and celiprolol.

Celiprolol is a novel beta 1 selective adrenoreceptor blocker with partial beta 2 agonism and direct vasodilator activity. These ancillary properties may reduce symptomatic breathlessness and fatigue and modify respiration during exercise. To test this hypothesis 20 men with stable effort angina were enrolled in a double-blind crossover study to investigate the effects of atenolol 100 mg once daily (A) and celiprolol 400 mg once daily (C) on cardiorespiratory and symptomatic variables during maximal and submaximal exercise. Total exercise time on a modified Bruce protocol was similar on both treatments: C12.5 min, A 13.1 min. During steady state submaximal exercise at 60-75% (mean 68%) of maximum work capacity, minute ventilation (C33.81 min-1, A 33.51 min-1), oxygen uptake (C14.6 ml.kg-1.min-1, A15.1 ml.kg-1.min-1), respiratory exchange ratio (C 0.89, A 0.87), ratio of VE/VCO2 (C 33.6, A 33.4), ratio of VE/VO2 (C 2.34, A 2.72), Borg perceived exertion score (C 11.2, A 10.9) and visual analogue scores for breathlessness (C 29.5, A 25.9) and muscle fatigue (C 28.9, A 26.0) were all similar on both treatments. At maximal exercise capacity on the modified Bruce protocol, minute ventilation (C 58.31 min-1, A 60.41 min-1), oxygen uptake (C 21.3 ml.kg-1.min-1, A 21.7 ml.kg-1.min-1), respiratory exchange ratio (C 1.02, A.1.05), ratio VE/VCO2 (C 34.8, A 35.9), and ratio VE/VO2 (C 2.80, A 2.83) were also similar on both drugs. Over a 10 day period anginal attacks (C 10.1 +/- 10.4, A 5.4 +/- 5.9) and sublingual GTN use (C 5.9 +/- 10.3, A 4.4 +/- 9.8) were both more frequent on celiprolol).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Pacemaker failure induced by radiotherapy.

It is well documented that radiation therapy can have significant transitory and permanent effects on the function of cardiac pacemakers. In this study 18 multiprogrammable pacemakers were tested to establish any pattern by which these pacemakers are affected. The results confirm previous predictions on how pacemakers are damaged. The damage could be divided essentially into three types: (1) temporary change to interference or safety mode pacing lasting for the duration of the irradiation only; (2) change to interference mode pacing--from which recovery may occur after reprogramming the pacemaker; and (3) severe damage; in this case the pacemaker stops generating pulses. Recovery from this may occur a long time after the end of the treatment, but this recovery is mostly incomplete and the pacemaker cannot be used reliably thereafter. Therefore it is essential that patients with implanted pacemakers undergoing radiation therapy, should be monitored closely during the course of the treatment and for a few weeks thereafter.

Electromagnetic Fields

Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides.

To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human alpha-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require approximately 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAP- and thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombin- and TRAP-treated surgical incisions. Thus, alpha-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management of wound healing in man.

Amino Acid Sequence

Sleep shift dissociates the nocturnal peaks of parathyroid hormone (1-84), nephrogenous cyclic adenosine monophosphate, and prolactin in normal men.

The secretion of PTH(1-84) and PRL over a 24-h period in normal subjects has been shown to be highly correlated, with changes in PRL occurring approximately 2 h after those in PTH(1-84). It has been postulated that there may be neuroendocrine control common to PTH(1-84) and PRL. As the secretion of PRL is known to be strongly influenced by sleep we investigated the effect of a 7-h acute sleep shift on the nocturnal secretion of PTH(1-84), PRL, and nephrogenous cAMP, a marker of PTH(1-84) bioactivity. Six normal male subjects were studied on two occasions (study A sleep, 0100-0800 h; study B, 0800-1400 h) with samples withdrawn at 30-min intervals. Sleep shift produced the expected shift in PRL secretion to new time of sleep. The overall timing of the PTH(1-84) nocturnal peak (0200-0600 h) was not altered by sleep shift. However, the start of the rise in PTH(1-84) (0200-0300 h) was blunted (P less than 0.05), and the peak of nephrogenous cAMP, coincident with the nocturnal rise in PTH(1-84) in study A, was markedly attenuated (P less than 0.01). Thus whereas the results of this study argue against a direct neuroendocrine link between PTH(1-84) and PRL, it is postulated that sleep shift disrupts a high degree of temporal organization which, under normal conditions, may allow concerted metabolic effects between PTH(1-84) and other hormones over a 24-h period.

Adult

Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction.

In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Subconjunctival high dose plasminogen activator in rabbit filtration surgery.

The primary cause of failure in glaucoma filtration surgery is fibroblastic proliferation and subconjunctival fibrosis at the bleb site resulting in decreased aqueous flow. We evaluated New Zealand white rabbits in a masked, placebo controlled pilot study to determine the potential reduction of episcleral fibrosis at the surgical bleb site utilizing 0.3 mls of: balanced salt solution (n = 11); an inert gel delivery vehicle (n = 13); the gel delivery vehicle with incorporated recombinant tissue plasminogen activator (tpa; n = 14), 1 mg/ml. Statistical analysis of computer assisted area measurements from multiple histologic sections demonstrated a significant decrease in episcleral fibrosis in the t-PA group as compared to the two other groups (p less than 0.05). Results from the t-PA group did not demonstrate an effect on intraocular pressure. There was no clinical evidence of toxicity or healing complications in the t-PA group.

Animals

Locked intramedullary nailing of open tibial fractures.

We report the use of Grosse-Kempf reamed intramedullary nailing in the treatment of 41 Gustilo type II and III open tibial fractures. The union times and infection rates were similar to those previously reported for similar fractures treated by external skeletal fixation, but the incidence of malunion was less and fewer required bone grafting. The role of exchange nailing is discussed and a treatment protocol is presented for the management of delayed union and nonunion.

Adolescent