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Biomedical subjects

R Lane

Publications and source records attributed to R Lane.

At least 19 recordsLinked to original sources
PubMed1998

A test of the claim that plan rankings are determined by relative complication and tumor-control probabilities.

PURPOSE: This study tests an accepted claim regarding tumor control (TCP) and normal tissue complication (NTCP) probability functions. The claim is that treatment plans can be ranked using relative probabilities, even when the absolute probabilities are unknown. The assumption supports the use of probability models for plan optimization and the comparison of treatment techniques. METHODS: The claim was tested using a hypothetical model consisting of two tissues, and illustrated with clinical data. Plans were scored using the probability of uncomplicated tumor control. The scores of different plans were compared by fixing their relative risks for an individual tissue complication, but adjusting the absolute probability levels up or down. The tested claim is that the plan rankings should not change. RESULTS: In the two-tissue model, the rankings of competing plans were reversed by doubling all the probabilities. The preference ordering of lung cancer plans changed after the risk of pulmonary complication was reduced by 3-fold. In another site, the ranking of plans by overall complication-free probability was disturbed by errors that preserved the ordering of plans with respect to any individual complication. An adjustment of +/- 2.5% in the initial NTCP values for two tissues changed the direction in which a plan score moved in response to a fixed tradeoff in complication risk in an optimization search. CONCLUSIONS: Contrary to claims, plan rankings are not determined by the relative probabilities of adverse events. The effect on plan scores of trading one complication for another depends on the absolute levels of risk. Absolute errors in NTCP and TCP functions result in the wrong ranking of plans, even when relative probabilities are correct. An optimization routine based on TCP and NTCP calculations may be forced in the wrong direction by small errors in the probability estimates.

Humans↗
PubMed1998

Timing of recovery of lung function after severe hypoxemic respiratory failure in children.

OBJECTIVE: To describe the timing of recovery of lung function after severe acute hypoxemic respiratory failure (AHRF) in children. DESIGN: A serial observational follow-up study of clinical and lung function measurements up to 53 months after acute illness. SETTING: University pediatric intensive care unit in a national children's hospital. PATIENTS: Five critically ill children aged 5-14 years. INTERVENTIONS: None RESULTS: Clinical recovery: each patient required a 3-5 month convalescence before being able to attend full-time school because of lethargy and dyspnea. All patients developed wheeze 3-12 months after illness and four received long-term bronchodilator therapy. Lung function recovery: for both the forced vital capacity (FVC) and forced vital capacity in the first second (FEV1) four patients had abnormally low values, regaining only 60-70% of predicted values for their height and sex, and all of this improvement had occurred by 6-12 months after illness. Beyond this interval, patients remained on their same FVC and FEV1 centile. FEV1/FVC ratios were consistently within the normal range, indicating a predominantly restrictive defect. Changes in peak expiratory flow exhibited a time course of improvement similar to the other lung function tests. CONCLUSION: In children, pulmonary recovery after severe AHRF may occur for 6-12 months. A 1-year follow-up could offer a rational single point for assessment of outcome and long-term counselling of child and parents.

Adolescent↗
PubMed1998

Aortic reconstructive surgery for limb ischaemia: immediate and long-term follow-up to provide a standard for endovascular procedures.

PURPOSE: Aortobifemoral and aortobiliac bypass has been a preferred treatment of severe aortoiliac occlusive disease. Recently, endovascular procedures and unilateral bypass grafting have been introduced. We report the results of aortic reconstructive surgery over a 19-year period (1975-1994). METHODS: A total of 285 patients underwent surgery. Follow-up data from clinical notes, general practitioner questionnaire or phone interview was available in 93.3% (266/285). RESULTS: Of the total 68% were male (180/226) and the median age was 63 years (range 22-85 years). Indications for surgery were tissue loss/gangrene (n = 32), rest pain (n = 84), severe claudication (n = 40), moderate claudication (n = 110). Total of 177 bifurcated grafts, 51 iliofemoral, eight left/right aortofemoral, and 30 other procedures were performed. The median duration of follow-up was 49.8 months. Cumulative secondary graft patency for 2, 5 and 10 years was 97.7%, 95.9%, and 94.4%. The amputation rate was 4.5% (12/266). Early mortality occurred in eight of 266 patients (3%) and late mortality in 60 patients. The most common cause of late death was ischaemic heart disease (24/60 followed by cancer (14/60). Data was further analysed by type of graft, risk factors, complications and previous and subsequent surgery. In our experience, aortic reconstructive surgery is a successful option for the management of severe aortoiliac occlusive disease. The outcome of other methods of maintaining arterial patency should be measured against this standard.

Adult↗
PubMed1998

Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study.

AIM: Achondroplasia can result in respiratory difficulty in early infancy. The aim of this study was to document lung growth during infancy, together with the cause of any cardiorespiratory and sleep dysfunction. PATIENTS AND METHODS: Seventeen prospectively ascertained infants (14 boys and three girls) with respiratory symptoms starting before 1 year of age underwent clinical, sleep, and lung function studies. RESULTS: Three distinct groups were identified. Group 1 (n = 6) were the least symptomatic and only had obstructive sleep apnoea. Group 2 (n = 6) had obstructive sleep apnoea of muscular aetiology and, neurologically, hydrocephalus and a small foramen magnum were common. Group 3 (n = 5), the most severely affected group, all developed cor pulmonale, with three deaths occurring as a result of terminal cardiorespiratory failure. All five had obstructive sleep apnoea with a muscular aetiology (a small foramen magnum predominated) with severe or moderately severe gastro-oesophageal reflux. Initially, lung function studies found no evidence of restriction or reduced lung volumes standardised according to weight. However, with growth these infants had worsening function, with raised airway resistance and severe reductions in respiratory compliance. CONCLUSIONS: These groups appear to be distinct phenotypes with distinct anatomical aetiologies: "relative" adenotonsillar hypertrophy, resulting from a degree of midfacial hypoplasia (group 1); muscular upper airway obstruction along with progressive hydrocephalus, resulting from jugular foramen stenosis (group 2); and muscular upper airway obstruction, but without hydrocephalus, resulting from hypoglossal canal stenosis with or without foramen magnum compression and no jugular foramen stenosis (group 3). The aetiology of these abnormalities is consistent with localised alteration of chondrocranial development: rostral, intermediary and caudal in groups 1, 2, and 3, respectively.

Achondroplasia↗
PubMed1998

Breathing patterns in children with craniofacial dysostosis and hindbrain herniation.

In the past few years, hindbrain herniation has become recognized as a frequent feature of the child with syndromic craniofacial dysostosis. The clinical significance of hindbrain herniation in these disorders is unclear. Abnormalities of respiratory control have frequently been reported. The aim of the present study was to document the incidence of obstructive and central respiratory abnormalities during sleep in craniofacial syndromes with hindbrain herniation. We performed cardiorespiratory sleep studies during unsedated night-time sleep in a group of 13 children. Hindbrain herniation was confirmed by magnetic resonance imaging (MRI) and ranged 1.5-26.9 mm below the cranial base. Sleep studies revealed central respiratory pauses associated with important reduction of the arterial oxygen saturation (Sa,O2) in only two of 13 cases (minimum Sa,O2 86% and 87%). In contrast 10 of 13 children had some degree of upper airway obstruction (four mild, three moderate and three severe). Of the remaining three children, two had previous long-term tracheostomies. Changes in the breathing pattern were proportional to the severity of the obstruction and comprised increased respiratory efforts and arterial oxygen desaturation. Infrequent mixed apnoeas were observed in five patients, and their severity reflected the severity of the obstructive component. In conclusion, obstruction of the upper airways was the predominant sleep-related respiratory problem in this group of patients. Hindbrain herniation was not associated with a high incidence of central sleep apnoea.

Airway Obstruction↗
PubMed1998

Torsional injury resulting in disc degeneration: I. An in vivo rabbit model.

Torsional injuries may be a precursor to intervertebral disc degeneration, but published rabbit models indicate a latent time of 6 months. We describe a rabbit model in which instability and disc degeneration appear within 3 months. Sixty-five male New Zealand rabbits underwent presurgical irradiation to inhibit heterotopic bone formation. Control animals then underwent either a soft-tissue release or facetectomy and capsulotomy, whereas experimental animals received surgery and an acute 30 degrees torsional lumbar injury. Capsulotomy, as well as facetectomy without torsion, failed to effect disc degeneration. However, the rabbits that received torsion exhibited clear indications of degenerative disc changes (thinning, increased PLA2 levels, and decreased nucleus pulposus volume) within 60-90 days. The observations associate disc degeneration with a destabilizing acute torsional injury.

Animals↗
PubMed1997

Selective serotonin reuptake inhibitor-induced serotonin syndrome: review.

The selective pharmacology of the selective serotonin reuptake inhibitors (SSRIs) results in a lower potential for pharmacodynamic drug interactions relative to other antidepressants such as the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). However, the SSRIs have been implicated in the development of the serotonin syndrome--a potentially life-threatening complication of treatment with psychotropic drugs. The syndrome is produced most often by the concurrent use of two or more drugs that enhance central nervous system serotonin activity and often goes unrecognized because of the varied and nonspecific nature of its clinical features. The serotonin syndrome is characterized by alterations in cognition (disorientation, confusion), behavior (agitation, restlessness), autonomic nervous system function (fever, shivering, diaphoresis, diarrhea), and neuromuscular (ataxia, hyperreflexia, myoclonus) activity. The difference between this syndrome and the occurrence of adverse effects caused by serotonin reuptake inhibitors alone is the clustering of the signs and symptoms, their severity, and their duration. There are important pharmacokinetic interactions between SSRIs and other serotonergic drugs due principally to their effects on the cytochrome P450(CYP) isoenzymes, the potential for which varies widely amongst the SSRI group, which may increase the likelihood of a pharmacodynamic interaction. The exceptionally long washout period required after fluoxetine discontinuation may cause additional problems and/or inconvenience. Patients with serotonin syndrome usually respond to discontinuation of drug therapy and supportive care alone, but they may also require treatment with antiserotonergic agent such as cyproheptadine, methysergide, and/or propranolol. To reduce the occurrence, morbidity, and mortality of the serotonin syndrome, it must be both prevented by prudent pharmacotherapy and given prompt recognition when it is present.

Antidepressive Agents↗
PubMed1997

Upper airway obstruction and raised intracranial pressure in children with craniosynostosis.

In children with craniosynostosis, raised intracranial pressure (ICP) and upper airway obstruction (UAO) are both common features. However, potential interactions between UAO and ICP during sleep are poorly understood. The aim of the present study was to compare the levels of ICP during sleep between a group of patients with syndromic craniosynostosis (with facial involvement and consequent UAO) and a group of control patients with isolated unicoronal synostosis (with no facial involvement and normal upper airways). Polygraphic cardiorespiratory sleep studies with continuous monitoring of ICP were performed during unsedated sleep in 13 children with syndromic craniosynostosis and 7 control patients with isolated unicoronal synostosis only. In the syndromic group, UAO was present in 11 out of 13 patients, with 8 out of 13 having frank obstructive sleep apnoea. In contrast, none of the control patients showed signs of UAO during sleep. There was no evidence of central apnoeas in any of the patients studied. Clinical histories taken from parents tended to underestimate the severity of the respiratory problems. Elevated ICP was seen in 10 of the 13 syndromic patients, with borderline raised ICP in the remaining three cases. In contrast, raised ICP was seen in only 3 of the 7 control patients, with borderline raised levels in 2 of the 7. For both patient groups, ICP was higher during active sleep compared to quiet sleep. Multiple regression analysis showed that ICP during active sleep was dependent upon disease severity (unicoronal/ multiple synostosis) and to the baseline ICP level during quiet sleep. Both raised ICP and airway obstruction were more apparent during active sleep. There was a significant correlation between severity of UAO and increased ICP in active sleep. We conclude that obstructive respiratory problems are frequent in the syndromic patients, and can be severe in a large proportion of cases; intracranial hypertension is also frequent in this group. Further studies are required to investigate the possibility of a causal relationship between upper airway obstruction and raised intracranial pressure.

Child↗
PubMed1996

Treatment of obstructive sleep apnoea using nasal CPAP in children with craniofacial dysostoses.

We studied a group of children (aged 2.2-15 years) with craniofacial dysostosis and obstructive sleep apnoea to assess the use of nasal continuous positive airway pressure (n-CPAP) as a palliative form of treatment. A variable period of time was allowed for acclimatisation to n-CPAP (1 day to 2 months), depending on the patient. Patients were then admitted for their first CPAP trial. Baseline breathing difficulty and the effectiveness of n-CPAP were assessed by respiratory sleep studies. Successful results were obtained with n-CPAP in five of the eight patients, with marked clinical and polygraphic improvements of the respiratory pattern immediately after n-CPAP was established. Of the remaining three cases, one child needed a prolonged period of acclimatisation to the n-CPAP system, one was withdrawn from the study, and one failed to respond to n-CPAP and was found to have complete blockage of the upper airways as a result of enlarged adenoids. Our results confirm that n-CPAP can be tolerated even by young patients and can be effective, and that it may be a useful alternative palliative treatment for obstructive sleep apnoea in children with craniofacial syndromes.

Adolescent↗
PubMed1996

Ruptured abdominal aortic aneurysms: who should be offered surgery?

PURPOSE: Operation for ruptured abdominal aortic aneurysm is generally still associated with a high mortality rate. A review of our experience over a 9-year period was undertaken to identify factors present on admission associated with 30-day operative mortality. METHODS: A retrospective analysis of 154 patients with ruptured abdominal aortic aneurysm submitted for operation in a university teaching hospital between January 1985 and December 1993 was undertaken. RESULTS: The hospital mortality rate was 39%. Logistic regression identified a set of five independent preoperative factors associated with mortality: age (> 76 years), creatinine level (> 0.19 mmol/L), loss of consciousness after arrival, Hb (< 9 g%), and electrocardiographic ischemia. In the 52 patients with a single risk factor present, the mortality rate was 37%, with two factors (32 patients) it was 72%, with three or more factors (8 patients), it was 100%, and no patient had all five risk factors. A 16% mortality rate was found in the 62 patients with no risk factors. CONCLUSION: These risk factors can be easily determined on admission and may be used to help improve patient selection for surgical intervention. The current operative mortality rate for ruptured abdominal aortic aneurysm remains high, and in some cases health care resources are used in a nonproductive fashion. Restricted patient selection and allocation of scarce resources will bring advantages to both the patient and the community.

Aged↗
PubMed1996

Treatment of preterm labor with the oxytocin antagonist atosiban.

The purpose of this study was to describe the course of preterm labor in patients receiving a standard intravenous infusion of the oxytocin antagonist atosiban. An open-labeled, non-randomized study was conducted at 4 sites. Successful tocolysis was defined as delay of delivery larger than 48 hours from starting atosiban and no need for an alternate tocolytic. Atosiban was administered by continuous intravenous infusion at a rate of 300 micrograms per minute until uterine contractions were absent for 6 hours, or up to a maximum infusion time of 12 hours. Sixty-two patients of between 20 and 36 weeks' gestation were enrolled over 6 months. One had rupture of membranes and was excluded. Successful tocolysis was noted in 43 of 61 (70.5%). Four delivered spontaneously within 48 hours and 14 (23.0%) required an alternate tocolytic agent. The chance of successful tocolysis was related to the degree of cervical dilation at the start of therapy. Cessation of uterine contractions was noted in 38 patients (62.3%). A decrease in uterine contraction frequency of 50% or more was noted in 50 of 61 patients (82.0%). Four patients reported side effects (nausea, vomiting, headache, dysguesia, chest pain), but in no case did side effects require discontinuation of the medication. Intravenous administration of atosiban is associated with a delay in delivery comparable to that seen with other tocolytics. If this effect is confirmed in planned placebo-controlled trials, its favorable side effect profile may give it a place in the armamentarium.

Adult↗
PubMed1996

A comparison of mixed integer programming and fast simulated annealing for optimizing beam weights in radiation therapy.

Two competing methods for assigning intensities to radiation treatment beams were tested. One method was derived from mixed integer programming and the other was based on simulated annealing. The methods faced a common objective and identical constraints. The goal was to maximize the minimum tumor dose while keeping the dose in required fractions of normal organ volumes below a threshold for damage. The minimum tumor doses of the two methods were compared when all the dose-volume constraints were satisfied. A mixed integer linear program gave a minimum tumor dose that was at least 1.8 Gy higher than that given by simulated annealing in 7 of 19 trials. The difference was > or = 5.4 Gy in 4 of 19 trials. In no case was the mixed integer solution one fraction size (1.8 Gy) worse than that of simulated annealing. The better solution provided by the mixed integer program allows tumor dose to increase without violating the dose-volume limits of normal tissues.

Abdominal Neoplasms↗
PubMed1996

A generic genetic algorithm for generating beam weights.

A genetic algorithm for generating beam weights is described. The algorithm improves an objective measure of the dose distribution while respecting dose volume constraints placed on critical structures. The algorithm was used to select beam weights for treatment of abdominal tumors. Weights were selected for up to 36 beams. Dose volume limits were placed on normal organs and a dose inhomogeneity limit was placed on tumor. Volumes were represented as sets of several hundred discrete points. The algorithm searched for the beam weights that would make the minimum tumor dose as high as the constraints would allow. The results were checked using dose volume histograms with standard sized grids. Nineteen trials were created using six patient cases by changing the required field margin or allowed beam position in each case. The sampling of points was sufficiently dense to yield solutions that strictly satisfied the constraints when the prescribed dose was renormalized by a factor of less than 6%. The genetic algorithm supplied solutions in 49 min on average, and in a maximum time of 87 min. The randomized search does not guarantee optimality, but high tumor doses were obtained. An example is shown for which the solution of the genetic algorithm gave a minimum tumor dose 7 Gy higher than the solution given by a simulated annealing algorithm under the same set of constraints. The genetic algorithm can be generalized to admit nonlinear functions of the beam intensities in the objective or in the constraints. These can include tumor control and normal tissue complication probabilities. The genetic algorithm is an attractive procedure for assigning beam weights in multifield plans. It improves the dose distribution while respecting specified rules for tissue tolerance.

Abdominal Neoplasms↗
PubMed1995

Plasma separation for artificial liver support.

A bioartificial liver (BAL) support system, using plasma separation, has been developed to support acute liver failure patients. This study examined 14 consecutive BAL treatments in nine patients with severe acute liver failure. We report methods to achieve and manage plasma separation for an extended period of time. The mean duration of a BAL treatment was 435 minutes, with 26-59 liters of blood processed. Ionized hypocalcemia resulting in muscle twitching was a side effect of the therapy. Ionized calcium levels decreased significantly (P < .02) after BAL treatment; however, total calcium levels increased (P < .05). No significant changes were noted in heart rate, electrocardiogram [Q-T (Q-Tc) interval], blood pressure, prothrombin time, partial thromboplastin time, hematocrit, platelet count and serum phosphorous, magnesium, glucose, and pH. Plasma fibrinogen levels decreased significantly (P < .002). Ionized hypocalcemia due to the chelating effect of sodium citrate was controlled by calcium chloride administration, adjustment of blood separation rates, and reduction of the blood-to-citrate ratio. This report demonstrates that intensive, large-volume plasma separation for long periods of time can be achieved safely in critically ill patients without serious adverse effects.

Adolescent↗