Impact of the recommendations of the British Pacing and Electrophysiology Group on pacemaker prescription and on the immediate costs of pacing in the Northern Region.

The report from the Working Party of the British Pacing and Electrophysiology Group recommends the use of more sophisticated pacemakers in most patients. These proposals were initially circulated in September 1990 and are likely to have major cost implications. Their impact on pacing practice and the immediate costs of pacemaker hardware in the Northern Region were retrospectively audited. The pacing records of 550 patients undergoing a first pacemaker insertion at the Freeman Hospital between March 1990 and August 1991 were reviewed. The patient's age, indication for pacing, pacing mode, and the cost of generator and lead(s) were recorded. The cost was compared with the costs of pacing with the optimal and alternative modes recommended by the Working Party. The costs were calculated from the actual mean cost of the recommended unit over the 18 month period of study multiplied by the number of patients who would have received that unit. 96% of patients were paced for sinus node dysfunction, atrioventricular block, or atrioventricular block and atrial fibrillation. The mean (SD) ages of patients in each diagnostic group were: sinus node dysfunction 69.4 (14), sinus node disease and atrioventricular block 67.2 (17.6), atrioventricular block 73.9 (12.5), atrial fibrillation and atrioventricular block 74.0 (13.9), and carotid sinus hypersensitivity 74.6 (11.6) years. Over the 18 month audit period there was an increase in physiological pacing. AAI pacing in patients with sinus node dysfunction increased by 100% and DDD pacing in atrioventricular block increased by atrioventricular block increased by 56%. Over the whole 18 month period the adoption of the British Pacing and Electrophysiology Groups optimal recommendations would have increased expenditure on pacemaker hardware in the Northern Region by 94% and the use of the alternative mode would have increased it by 61%. For the last six months alone the excess would be 78% and 48%. The adoption of the recommendations of the British Pacing and Electrophysiology group in the Northern Region would greatly increase the cost of pacing hardware. The greater part of this increase would be attributable to the routine use of dual chamber pacing in patients with atrioventricular block and the increased use of rate responsive units. The benefits of sophisticated pacing in a predominantly elderly population need to outweigh the disadvantages of the increased cost and complexity of follow up.


Adaptation of the maternal heart in pregnancy.

The first haemodynamic change during pregnancy seems to be a rise in heart rate. Starting between two and five weeks this continues well into the third trimester. Stroke volume increases slightly later than the heart rate and continues throughout the second trimester after an augmentation of venous return and a fall of systemic vascular resistance and afterload. Myocardial contractility is probably slightly increased. During the third trimester there is relatively little change in these cardiac indices. After delivery there is a very early and dramatic reduction in volume loading followed by a return towards normal cardiac output. Structural changes within the heart reflect the volume loading of pregnancy and include dilatation of the valve ring and increase in myocardial thickness. Post partum resolution of the ventricular hypertrophy seems to take longer than the rest of the post partum changes. The resemblance to the cardiovascular changes associated with training and exercise are fascinating and worthy of further study.


Effect of exercise training on the total ischaemic burden: an assessment by 24 hour ambulatory electrocardiographic monitoring.

To examine the effect of prolonged high intensity exercise training on total ischaemic burden in men with chronic stable angina pectoris. A randomised controlled trial based on 24 hour ambulatory electrocardiographic monitoring of patients on two occasions a year apart. Cardiology department of a large general hospital. 40 men under 60 years of age with chronic stable angina pectoris and no previous myocardial infarction. After training the exercise group showed a 30% reduction in frequency of ST segment depression. There were significant reductions in painful episodes of ischaemia and those triggered by changes in heart rate. There was also a trend towards a reduction in silent ischaemia and episodes not triggered by changes in heart rate. The duration of ischaemic episodes was also reduced. No significant change in frequency or severity of dysrhythmia was shown. Exercise training reduces total ischaemic burden in patients with angina pectoris by reducing the frequency and duration of all types of ischaemic episode.


Relation of left ventricular isovolumic relaxation time and incoordination to transmitral Doppler filling patterns.

To investigate factors during isovolumic relaxation that determine Doppler filling patterns in patients with left ventricular disease, and thus to identify the underlying mechanisms. 85 patients (50 ischaemic heart disease, 35 left ventricular hypertrophy due to aortic stenosis) and 26 controls were studied with Doppler and M mode echocardiography and phonocardiography. 16 patients underwent two studies on separate occasions, to find whether changes in isovolumic relaxation time were reflected by a change in the Doppler A/E ratio. A tertiary cardiac referral centre. Patients referred for assessment of coronary artery disease or aortic stenosis with left ventricular hypertrophy. Doppler filling velocities during early (E wave) and late (A wave) diastole and the A/E ratio, acceleration of the E wave, digitised M mode indices of incoordinate relaxation (change in cavity dimension before mitral valve opening and time from minimum dimension to mitral valve opening), isovolumic relaxation time, M mode measures of diastolic function after mitral valve opening (peak rate of posterior wall thinning and peak rate of dimension increase), and left ventricular end diastolic pressure. A/E correlated with age in normal subjects (r = 0.74), to a lesser extent in left ventricular hypertrophy (r = 0.41), but not significantly in ischaemic heart disease. In all patients, isovolumic relaxation time was significantly and negatively correlated with the acceleration of the E wave, showing its fundamental relation to the force responsible for early diastolic filling (r = -0.71 for left ventricular hypertrophy, and -0.74 for ischaemic heart disease, p value < 0.01). In left ventricular hypertrophy and those ischaemic patients without left ventricular dilatation A/E was correlated both with isovolumic relaxation time (r = 0.68 and 0.60 respectively), and with incoordinate relaxation (r = 0.65 and 0.61). In those ischaemic patients with left ventricular dilatation, the influence of incoordination was lost and isovolumic relaxation time became the dominant influence upon A/E (r = 0.82). Weak correlations of end diastolic pressure and RR interval with A/E, became insignificant once isovolumic relaxation time had been taken into account. Isovolumic relaxation time and incoordination together accounted for over 50% of the variance in the A/E ratio in our patients. Isovolumic relaxation time and the A/E ratio were linearly related. Patients with a short isovolumic relaxation time had evidence of considerable diastolic abnormalities, despite a normal Doppler A/E ratio. In the 16 patients who had two echocardiographic studies, changes in the duration of isovolumic relaxation were accompanied by a change in the Doppler A/E ratio. The relation between these two variables, derived from the group as a whole was similar. The main factors influencing the A/E ratio in patients with left ventricular disease are two distinct properties of isovolumic relaxation--namely the duration and the extent of incoordinate wall motion. Filling pressure and RR interval are not significant independent determinants, but act only through an effect upon isovolumic relaxation time. Age is an important influence in normal people, but this effect is attenuated in left ventricular hypertrophy and lost in ischaemic ventricular disease.


Analysis of left ventricular regional wall motion in normal neonates.

To investigate neonatal circulatory change by quantitative analysis of left ventricular regional wall motion. Random prospective study. Department of paediatrics in a teaching hospital. 66 neonates born after a normal pregnancy, labour, and delivery. Quantitative analysis of left ventricular regional wall motion was performed on cross sectional echocardiograms. M mode, cross sectional, and Doppler echocardiograms were obtained simultaneously. Manually traced endocardial contours at end diastole and at end systole were realigned by superimposing the centre of the ventricular mass and the axis. The contours were divided into 24 segments with 24 radii of equal arc from the centre. Then the ratio of the change in area between the outline of the contour and the two hemiaxes was calculated automatically. There was hyperkinesis of the interventricular septum in the first 24 hours after birth which continued until the end of the first week. Simultaneous echocardiographic examination showed evidence of pulmonary hypertension, as indicated by an increase in the ratio of the right pre-ejection period to the right ventricular ejection time (RPEP/RVET) and of the diameter ratio of the pulmonary artery to the aorta and a shortening of the acceleration time of pulmonary arterial blood flow. These features disappeared within a week. Hyperkinesis of the interventricular septum may reflect circulatory changes that are characteristic of the early neonatal period.


Correlation between echocardiographic and morphological investigations of lesions of the tricuspid valve diagnosed during fetal life.

To assess the degree of agreement between the fetal echocardiographic and postmortem examination of hearts from fetuses with severe malformations of the tricuspid valve. A retrospective study to analyse echocardiographic recordings and make comparisons with postmortem findings. Tertiary referral centre for fetal echocardiography. Institute for cardiac morphology. 19 cases shown to have severe malformation of the tricuspid valve by fetal echocardiography that died in the prenatal or neonatal period. Correlations between morphology and measurements made at echocardiography and necropsy. The echocardiographic diagnosis was Ebstein's malformation in seven and tricuspid valvar dysplasia in 12 fetuses. These findings were confirmed in six and eight cases at necropsy. In one false positive diagnosis of Ebstein's malformation, necropsy showed dysplasia of the leaflets of the tricuspid valve without displacement. In four cases with the echocardiographic diagnosis of valvar dysplasia, necropsy showed displacement, the hallmark of Ebstein's malformation. Associated malformations that are known to worsen prognosis were predicted correctly by echocardiography. Taking the mean duration of four weeks between echocardiographic and postmortem investigations, both methods showed cardiomegaly causing lung hypoplasia, right atrial dilatation, and relative hypoplasia of the pulmonary trunk, morphometric factors that may be responsible for the poor outcome. Mostly good agreement existed between the echocardiographic and postmortem measurements if cases with an interval of more than eight weeks between the measurements were excluded. Fetal echocardiography was proved to be a reliable technique in differentiating the variants of tricuspid valvar disease, in diagnosing associated cardiac lesions, and in predicting quantitative factors that can define the subsequent outcome.


Myocardial disarray in Noonan syndrome.

To characterise the histopathology of the left ventricular hypertrophy commonly associated with Noonan syndrome by assessing the extent of myocyte disarray and therefore to define one aspect of the relation between this disease and idiopathic hypertrophic cardiomyopathy. Blinded histological analysis. Hospital medical school. Six hearts of children with the Noonan phenotype and isolated ventricular hypertrophy were compared with age and sex matched controls. Histological analysis was performed with an image analyser under light microscopy. Representative sections from the entire left ventricular free wall were examined. Results were expressed as the percentage of fields showing disarray related to the number of fields evaluated: 100 fields were examined for each patient. In the patients with Noonan syndrome myocardial disarray was present in the ventricular septum in 24 (5.7)% (mean (SD)) of fields and in the free wall in 22.2 (6.8)%. In the controls disarray was present in the septum in 3.8 (2.3)% of fields and in the free wall in 2.4 (2.8)%. In both regions the extent of disarray was significantly greater in patients with Noonan syndrome (p < 0.0005; 95% confidence interval 14 to 26.3 for the septum: p < 0.005, 95% confidence interval 11.4 to 28.2 for the free wall). The ventricular hypertrophy associated with Noonan syndrome is histologically similar to hypertrophic cardiomyopathy but whether the two diseases are the expression of the same genetic defect remains to be determined.


Different distribution of abnormal endocardial electrograms within the right atrium in patients with sick sinus syndrome.

Prolonged and fractionated right atrial endocardial electrograms are characteristic of paroxysmal atrial fibrillation (idiopathic or associated with sick sinus syndrome). The distribution of these abnormal atrial electrograms within the right atrium and the way it is related to the likelihood that patients with sick sinus syndrome will develop paroxysmal atrial fibrillation was studied. Endocardial catheter mapping of the right atrium during sinus rhythm was performed in 41 control patients with normal sinus node function and without paroxysmal atrial fibrillation, in 33 patients with sick sinus syndrome but without tachycardia, and in 27 patients with sick sinus syndrome and paroxysmal atrial fibrillation (group 3). The bipolar electrograms were recorded at 12 sites in the right atrium and an abnormal atrial electrogram was defined as lasting > or = 100 ms and/or showing eight or more fragmented deflections. 1195 atrial endocardial electrograms were assessed and quantitatively measured. In patients with sick sinus syndrome and paroxysmal atrial fibrillation 54% of the abnormal atrial electrograms were recorded from the high right atrium, 28% from the mild right atrium, and 18% from the low right atrium. However, in patients with sick sinus syndrome without tachycardia 78% of the abnormal atrial electrograms were recorded from the high right atrium and 22% from the mid right atrium. No abnormal electrograms were recorded from the low right atrium. In patients with sick sinus syndrome without tachycardia abnormal atrial electrograms generally came from the high right atrium but in patients with sick sinus syndrome and paroxysmal atrial fibrillation abnormal atrial electrograms were more widely distributed in the right atrium. In patients with sick sinus syndrome the greater the extent of the compromised atrial muscle, the greater the likelihood that paroxysmal atrial fibrillation will develop.


Non-atherosclerotic coronary artery disease and sudden death in the young.

To assess prevalence and type of non-atherosclerotic coronary artery disease in young people (< or = 35 years) who died suddenly. A necropsy study of 150 consecutive cases of sudden death (that is, within 6 h of the onset of symptoms). Death was attributed to coronary artery disease in 48 cases: in 16 (33%) of them the disease was non-atherosclerotic. Twelve subjects (eight males and four females, age range 2-35 years, mean 24.2) had congenital anomalies: a deep intramyocardial course in six, origin from the wrong sinus in three, and ostial obstructions in three. Sudden death was the first manifestation of disease in six cases. The other six had a history of palpitation or syncope or both. An electrocardiogram was available in five cases and showed ventricular arrhythmias in four; none had angina pectoris. Stress testing was available in two cases: neither showed any effort-dependent ST-T abnormalities. In six cases sudden death was related to physical exercise. Acquired non-atherosclerotic coronary artery disease was found in four cases: spontaneous coronary dissection in three previously symptom free patients and Kawasaki coronary arteritis in one child who had had acute myocardial infarction. One third of the cases of fatal coronary artery disease were non-atherosclerotic with coronary artery anomalies being the most frequent form. Coronary artery anomalies should be suspected in young patients who have symptoms of ventricular arrhythmias without any overt signs and symptoms of ischaemia.


Percutaneous balloon pericardiotomy in the management of recurrent malignant pericardial effusions.

Two patients with recurrent symptomatic pericardial effusions secondary to malignant disease were successfully treated by percutaneous balloon pericardiotomy. Open surgery was avoided and the procedure was completed under local anaesthesia in less than 40 minutes. The first patient was free of recurrence at nine months but pericardial effusion recurred at two months in the second patient. Percutaneous balloon pericardiotomy offers a potentially important new means of relieving recurrent tamponade and substantially reduces trauma to the patient.


Adjustment for the influence of age and heart rate on Doppler measurements of left ventricular filling.

To determine the normal range of pulsed Doppler measurements of left ventricular filling adjusted for age and heart rate. Multiple regression was used to measure the effects of age and heart rate on pulsed Doppler indices of left ventricular filling in normal subjects. These regression equations were used to calculate a predicted normal value and 95% confidence interval (95% CI) for any subject from his age and heart rate. 61 subjects with no evidence of cardiovascular disease, aged 20 to 90 years, with a resting heart rate of 47-89 beats/min. The effect of a 10 year increase in age was peak atrial filling velocity +15% (95% CI 12.0% to 18.5%); peak early filling velocity -3.2% (-6.0% to 0%); isovolumic relaxation time +6.2% (3.9% to 8.4%); acceleration time -3.8% (-6.0% to -1.5%); deceleration time +7.9% (5.1% to 10.8%). The effect of a 10 beat/min increase in heart rate was: peak atrial filling velocity +5.5% (1.2% to 10.1%); peak early filling velocity -4.0% (-8.1% to 2.0%); isovolumic relaxation time -2.5% (-4.6% to 0.6%); acceleration time -3.1% (-6.4% to 0.4%); deceleration time -1.8% (-4.0% to 3.8%). For any individual, comparison of the predicted normal measurement and 95% CI with the observed measurement allows an assessment of the effects of disease on left ventricular filling that is independent of age and heart rate.


Pulmonary artery rupture in pregnancy complicating patent ductus arteriosus.

Fatal haemopericardium in a 27 year old pregnant woman was caused by rupture of a dissecting aneurysm of the pulmonary artery. She had an uncorrected patent ductus arteriosus and severe pulmonary hypertension. The wall of the pulmonary artery showed atherosclerosis and cystic medionecrosis.


Leaking false aneurysm of right coronary saphenous vein graft; successful treatment by percutaneous coil embolisation.

An unusual complication after aortocoronary bypass grafting (CABG) is described in which a false aneurysm of the saphenous vein graft to the right coronary artery (RCA) developed and caused profuse intermittent bleeding through the sternotomy wound. The aetiology of this condition is uncertain but it could occur whenever a suture line is present especially in the presence of infection. The diagnosis was made non-invasively by a contrast enhanced computed tomogram and was subsequently confirmed by selective coronary bypass angiography. The pseudoaneurysm was successfully obliterated by coil embolisation of the right coronary graft, which stopped the bleeding immediately and was followed by rapid wound healing.


Seventh survey of staffing in cardiology in the United Kingdom 1991. British Cardiac Society, the Cardiology Committee of the Royal College of Physicians, and the Trafford Centre for Medical Research, University of Sussex.

The Seventh Survey of Staffing in Cardiology was conducted with an index date of 31 July 1991. At that time the total number of posts for cardiologists in England and Wales, defined as individuals trained in the specialty and spending at least 40% of their professional time working in it, was 340. Ten individuals worked part time only, making 335 whole time equivalent posts. This number increased from 1990 by 15 (4.7%). There were 67 cardiologists in Scotland and Northern Ireland, making a total for the United Kingdom of 407 posts (402 whole time equivalents). Sixteen Districts in England and Wales had no cardiologist at the time of the survey, and 31 other Districts had less than seven visiting sessions each week. The situation had not improved since the 1990 survey. The population of these 47 Districts is nearly nine million. Scotland had almost 800,000 additional people served by Health Boards without resident cardiologists. The number of senior registrars and lecturers is inadequate to provide a full period of training for most who advance to consultant status, and the situation will worsen from 1995 onwards. A major problem has been a top slice of 10 posts for a research allocation, few of which are occupied by individuals seeking a career in the specialty. These posts should be redesignated to increase training opportunities to counter the present shortfall and facilitate an expansion in consultant posts of at least 5% per annum over the next decade.


The future of paediatric cardiology in the United Kingdom. British Cardiac Society and the Royal College of Physicians of London.

(1) The working party has considered the requirements for the training of paediatric cardiologists and has suggested a flexible curriculum that allows the specialty to benefit from doctors coming into it from both adult cardiological and paediatric disciplines. (2) The working party appreciates that the short term problem with appointment of paediatric cardiologists cannot be solved immediately and recommends that appointing authorities should show patience. They should look to the possibility of identifying suitable candidates, at present in training, and making proleptic appointments to allow appropriate training to be completed. (3) There is a need for an increase in the number of paediatric cardiologists to service the specialty during a period when the patient load will increase because of population trends and changes in work patterns (specifically adults with congenital heart disease and prenatal cardiology). The care of adults with congenital heart disease has to be planned, certainly at regional and probably supraregional levels, and the financial and training implication has to be recognised. (4) The working party therefore recommends that there should be one consultant paediatric cardiologist per million of the population to allow for these changes in the service. (5) The working party considers that this report makes a very strong case for an increase in the number of senior registrar and registrar posts in the specialty. The existing number of junior posts will not fill the increase in agreed new posts and those made vacant by retirements between now and the end of the decade. When the additional posts recommended by the working party are taken into account at least three new senior registrar posts are needed. To make sure that a satisfactory supply of experienced candidates is available to fill the senior registrar posts the working party recommends the provision of two full time middle grade registrar jobs for each senior registrar position.


Hemodialysis needles can be pain free: use of a topical anaesthetic cream.

Many patients on hemodialysis experience pain and anxiety related to fistula punctures. The purpose of this study was to investigate the analgesic effect of an anaesthetic (lidocaine/prilocaine) cream when used to alleviate pain from the insertion of hemodialysis needles. The study took place over a 12-month time frame with a total of seven patients participating in the study. Before the patient entered the study, an assessment was made by the nursing staff as to the degree of pain and/or anxiety experienced by the patient in relation to needling. Patients were instructed regarding application of the cream. We have found this cream to be an effective topical anaesthetic in preventing pain and alleviating anxiety associated with needling. All patients involved in the study have expressed the desire to continue use of the cream. Use of this topical anaesthetic could also have great ramifications for paediatric dialysis, venipunctures and other procedures requiring topical anaesthesia.


Peripheral nerve injury caused by injection needles used in regional anaesthesia: influence of bevel configuration, studied in a rat model.

We have studied the immediate and long term (up to 28 days) effects of short and long bevelled needle impalement of the rat sciatic nerve. Three techniques were used to assess neural trauma and its consequences: stained longitudinal nerve sections were assessed by light microscopy and scored for injury; the extravasation of Evan's Blue dye, after antidromic electrical nerve stimulation, was used as a test of unmyelinated fibre function; the flexion withdrawal times from a noxious stimulus were measured. The results of all three experiments suggested that, should a nerve fascicle become accidentally impaled during regional anaesthesia, the lesions induced by short bevelled needles are more severe, more frequent and take longer to repair than those induced by long bevelled needles. Nerve injury induced by short bevelled needles was associated with persisting signs of injury 28 days after the injury. These results suggest that the current practice of using short bevelled needles to prevent nerve injury complicating regional anaesthesia be reassessed.


Effect of age, sex and anaesthetic technique on the pharmacokinetics of atracurium.

We have defined the pharmacokinetics of atracurium besylate 0.25 mg kg-1 in 41 patients anaesthetized with 0.9% isoflurane end-tidal, 0.5% halothane end-tidal or midazolam 3-10 mg as a supplement to 66% nitrous oxide in oxygen. The pharmacokinetic profile was affected by age, sex and anaesthetic technique. Advancing age was associated with a reduced clearance and a longer elimination half-time; clearance was greater and elimination half-time was shorter in males than in females. Clearance was also greater in patients anaesthetized with isoflurane than with the two other techniques. Age, sex and anaesthetic technique did not significantly affect the volume of distribution.


Etomidate shortens the onset time of neuromuscular block.

We have studied 30 healthy patients allocated randomly to receive thiopentone, propofol or etomidate in equipotent doses followed by vecuronium 0.1 mg kg-1. Haemodynamic variables and time to 100% neuromuscular block were measured. The patients receiving etomidate had a significantly shorter onset time of neuromuscular block compared with those receiving the two other i.v. induction agents. There was a significant negative correlation between onset time of neuromuscular block and the maximum percent change in mean arterial pressure.


Disposition of alfentanil in burns patients.

We have studied the disposition of alfentanil in six patients (who had suffered 10-30% surface area burns 5-21 days previously) undergoing surgical debridement and grafting and compared the data with those from a control group of six patients matched for age, sex and weight undergoing body surface surgery of similar duration. Plasma samples were collected up to 480 min after an i.v. bolus of alfentanil 50 micrograms kg-1. Drug concentrations were measured by radioimmunoassay and alfentanil binding to plasma proteins by equilibrium dialysis. The burns patients had significantly greater concentrations of alpha-1-acid glycoprotein (AAG) and smaller concentrations of albumin. The mean protein binding of alfentanil was 94.2 (SEM 0.05)% in the burns group and 90.7 (0.4)% in the control group (P = 0.004). There was a good correlation between AAG concentration and protein binding (r = 0.8). The volume of distribution and total clearance of alfentanil were reduced significantly in the burns group. The clearance of the unbound fraction and the elimination half-life of alfentanil were not decreased significantly.


Effect of diclofenac on renal function and prostacyclin generation after surgery.

We have examined the effect of diclofenac on renal function after major surgery in a randomized, double-blind, controlled study of 20 patients undergoing oesophagogastrectomy. Diclofenac 75 mg or placebo was given i.m. 12-hourly for 2 days. I.v. fluid administration was standardized. Renal function was assessed by fluid balance and measurement of serum creatinine and electrolyte concentrations, creatinine and free water clearance, and urinary sodium and potassium excretion. Urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) was measured by radioimmunoassay to assess renal prostacyclin production. After surgery, 6-keto-PGF1 alpha production increased, but this did not occur with diclofenac. On the first day after surgery, use of diclofenac was associated with a decreased urine flow rate, decreased urinary sodium and potassium excretion and a tendency to hyperkalaemia. Frusemide was required more often in the diclofenac group. One patient was withdrawn from the diclofenac group because of impaired renal function. Urine flow rate and blood potassium concentration should be monitored if diclofenac is used after major surgery.


Mechanism of extension of spinal anaesthesia by extradural injection of local anaesthetic.

We have examined the effect of extradual injection of 0.5% bupivacaine or normal saline on the progression of spinal anaesthesia in 28 patients undergoing Caesearean section. Three groups were studied. Subarachnoid anaesthesia was established in all patients. Group A (n = 10), the control, received no extradural injection for 20 min. Group B (n = 9) received extradural bupivacaine 10 ml and group C (n = 9) received extradual saline 10 ml 5 min after the subarachnoid injection. Sensory levels were compared at 5-min intervals and extension of the block was found to be similar in groups B and C and significantly faster than the control (P < 0.05). The quality of anaesthesia and incidence of adverse effects was similar for all three groups. We conclude that the mechanism of extension of spinal anaesthesia by extradural injection of local anaesthesia is largely a volume effect.


Comparison of hypertonic saline (5%), isotonic saline and Ringer's lactate solutions for fluid preloading before lumbar extradural anaesthesia.

We have compared the haemodynamic effects of fluid preloading performed before lumbar extradural anaesthesia with isotonic saline (NS), 5% hypertonic saline (HS) and Ringer's lactate (RL) solutions in 30 ASA I patients undergoing minor orthopaedic surgery, allocated randomly to the three groups. All patients received an equal amount of sodium (2 mmol kg-1). After fluid preloading, lumber extradural anaesthesia was performed (2% lignocaine 6 mg kg-1) and ephedrine was administered in order to maintain mean arterial pressure (MAP) > 80% of its control value. Both volume and duration of fluid preload were significantly less in group HS (160 (SD 25) ml, 8.8 (SD 2.9) min) than in the two other groups (NS: 903 (144) ml, 17.7 (3.3) min; RL: 932 (166) ml, 212 (6.0) min) (P < 0.05). The number of blocked segments and the total amount of ephedrine administered were similar in the three groups. Heart rate increased significantly in all groups immediately after the fluid preload and remained increased until the end of the study (90 min). MAP was not affected by any fluid preload and its maximal decrease after lumbar extradural anaesthesia was similar in all groups. Infusion of 5% HS 2.3 ml kg-1 was tolerated well and produced a significant (P < 0.05) but moderate hypernatraemia lasting 90 min after the end of fluid preloading. We conclude that HS may be useful when rapid fluid preloading is desired, in situations where excess free water administration is not desired.


Cricoid pressure may prevent insertion of the laryngeal mask airway.

We have studied 42 female patients undergoing elective day-case surgery allocated randomly to two groups. After induction of anaesthesia an attempt was made to insert a laryngeal mask airway after application of cricoid pressure in one group or with no cricoid pressure in the other. The anaesthetist was unaware of the application, or not, of cricoid pressure. Successful insertion was achieved at the first or second attempt in 19 of the 22 patients in the non-cricoid pressure group, but in only three of the 20 patients in the cricoid pressure group (chi 2 18.62, P < 0.001). The laryngeal mask airway was then inserted successfully in all 17 patients after removal of cricoid pressure. The implications of having to remove cricoid pressure if a laryngeal mask airway is to be inserted are discussed.


Is the "K-type" caffeine-halothane responder susceptible to malignant hyperthermia?

The "K-type" designation is used to describe a patient being investigated for malignant hyperthermia (MH) when concurrent administration of caffeine and halothane induces muscle contracture (rigidity, spasm) in vitro, but when halothane and caffeine given separately produce a normal response. It is accepted in some centres that K-type individuals are susceptible to malignant hyperthermia (MHS). In this paper, the K-type is shown not to correlate with the MH susceptible (MHS) status as accepted by the European MH group.


Fractional delivery of fresh gas: a new index of the efficiency of semi-closed breathing systems.

In earlier clinical studies, we have found a significant difference in the fractional utilization of fresh gas (FU) when using an enclosed afferent reservoir breathing system (EAR) for adult patients compared with children. This difference was explained by a large arterial to end-tidal carbon dioxide difference in the adults, reflecting a larger alveolar deadspace. In the present study, a new index of breathing system efficiency, fractional delivery of fresh gas (Fd) is proposed, which is independent of alveolar deadspace. In order to demonstrate this, values of Fd were calculated for the EAR during controlled ventilation of adults, children and a lung model. There were no significant differences between the groups. A maximum efficiency of 0.94 for the EAR was close to the theoretical limit of 1.0 predicted by the results at minute volume ventilation to fresh gas flow ratio (VE:VF) values greater than 2.0. For adult patients, the values of Fd were shown to be significantly greater than the values of FU at the same VE:VF ratio (Fd = 0.91, FU = 0.72 at VE:VF = 2.0 (P < 0.05)).


Hepatic disposition of methohexitone in patients undergoing coronary bypass surgery.

In order to clarify the relative contribution of hepatic metabolism to the short term disposition of methohexitone, we have measured hepatic blood flow during induction of anaesthesia with a 1.5-mg kg-1 i.v. bolus dose of methohexitone. Median hepatic clearance was 1.01 litre min-1 and hepatic extraction 87%. As a consequence of the high hepatic extraction, the hepatic clearance of methohexitone was closely dependent on hepatic plasma flow.


Anaesthesia for critically ill children during magnetic resonance imaging.

Magnetic resonance imaging (MRI) is becoming increasingly useful in children. Because of technical considerations and safety concerns, critically ill children have frequently been excluded from MRI. We have accomplished safely both transport and MRI in 21 patients from paediatric intensive care units (ICU). Three children were not considered appropriate for transport from the ICU to the MRI facility. All patients underwent assisted ventilation using a modified Mapleson D system. Monitoring of oxygenation, ventilation and haemodynamic state, including invasive arterial (n = 4) and intracranial pressures (n = 3) was continued successfully using routinely available equipment. All MRI studies were completed successfully with satisfactory image quality and all patients returned to the ICU in satisfactory condition. In contrast with previous reports which have excluded critically ill children, we have demonstrated that MRI may be undertaken safely and efficiently in critically ill children.


Enhancement of bupivacaine toxicity by diltiazem in anaesthetized dogs.

We have studied the cardiovascular effects of graded doses of bupivacaine in the absence or presence of clinical concentrations (approximately 250 micrograms litre-1) of diltiazem in fentanyl-pentobarbitone anaesthetized dogs. Bupivacaine was given, increasing in a stepwise manner, as a loading dose (200, 400 or 600 micrograms kg-1) followed by a 30-min i.v. infusion (25, 100 or 200 micrograms kg-1 min-1, respectively). Thereafter, bupivacaine was infused at 400 micrograms kg-1 min-1 until each animal died. Group A (n = 7) received bupivacaine, group B (n = 5) diltiazem (400 micrograms kg-1 followed by 12 micrograms kg-1 min-1) and group C (n = 7) received diltiazem followed by bupivacaine given as in group A. Lethal plasma concentrations of bupivacaine were significantly smaller (P < 0.01) in group C (7.1 (SEM 0.7) vs 12.6 (1.5) mg litre-1). Bupivacaine produced similar decreases in cardiac index, left ventricular (LV) segmental work and the first derivative of LV pressure (LV dP/dt) in the absence and presence of diltiazem. In group A, bupivacaine increased systemic vascular resistance index (SVRI) and thus mean arterial pressure (MAP) was maintained. In group C, SVRI, reduced by diltiazem per se, did not increase in response to bupivacaine, so MAP was not maintained. Death resulted from a progressive decrease in cardiac contractility and MAP. Plasma concentrations of bupivacaine attained at the three doses were similar in the absence and presence of diltiazem. This study has shown that the toxicity of bupivacaine was increased approximately two-fold by diltiazem.


Plasma lignocaine concentrations associated with extradural analgesia in patients with and without multiple organ failure.

We have measured plasma concentrations of lignocaine after thoracic extradural analgesia with continuous infusion of lignocaine in eight intensive care patients with chest wall trauma or after major upper abdominal surgery. Four patients developed multiple organ failure (MOF). Plasma concentrations of lignocaine in arterial blood were measured 4, 8, 24 and 48 h after a continuous infusion of lignocaine was commenced in the extradural space. Plasma concentrations of lignocaine were greater in all patients with MOF (range 2.7-5.1 micrograms ml-1) than in patients without MOF (range 0.8-1.2 micrograms ml-1). Because plasma concentrations in patients with MOF were within the low toxic range, extradural infusion of lignocaine should only be considered in intensive care patients without MOF or when plasma concentrations of lignocaine are monitored.


Anaesthesia for caesarean section in a patient with Ehlers-Danlos syndrome type IV.

We report the successful use of combined spinal and extradural anaesthesia for elective Caesarean section in a primigravid patient with Ehlers-Danlos type IV (EDS IV). EDS IV is a rare disorder with a high pregnancy-related mortality. Previous reports have not addressed the question of anaesthesia for delivery. It is not possible to be didactic about anaesthetic technique for such patients. The relative risks of general and regional anaesthesia must be discussed fully, and the risks weighed against the wishes of the woman and her partner.


Abolition of the extradural sieve by addition of fentanyl to extradural bupivacaine.

A patient is described in whom breakthrough of pain occurred from uterine rupture during effective extradural analgesia, demonstrating the hypothesis of the "extradural sieve". Subsequent abolition of this pain by addition of fentanyl to bupivacaine 0.25% raises the question whether or not this combination should be avoided in women with a scarred uterus undergoing "trial of labour".


Bacterial retention properties of heat and moisture exchange filters.

We have examined the properties of six heat and moisture exchange filters (HMEF) to ascertain their resistance to liquid flow and their ability to retain a challenge bacterium, Pseudomonas diminuta, from aqueous and nebulized suspensions. Only one HMEF, the Pall Ultipor was able to withstand a significantly greater pressure of liquid than that found in clinical practice. However, when breached, the HMEF were unable to prevent transmission of micro-organisms from aqueous suspension. Only the Darex Hydrobac filter failed to meet the manufacturer's claim for filter efficiency for nebulized bacteria, mainly because the filter housing failed under test. When the reduction in bacterial cells after passage of the nebulized Pseudomonas diminuta through the HMEFs was analysed statistically, the data showed that the HMEF produced by Pall (Ultipor) and Intersurgical (Filter therm) were superior to those produced by DAR Mediplan (Hygrobac), Intertech (HME 225-2835-800) and Gibeck (Humid-vent).


Hypoxaemia and pain relief after lower abdominal surgery: comparison of extradural and patient-controlled analgesia.

We have examined postoperative pain in patients allocated randomly to receive extradural bolus diamorphine 3.6 mg, extradural infusion of 0.15% bupivacaine with 0.01% diamorphine or patient-controlled i.v. administration of diamorphine at a maximum rate of 1 mg per 5 min, after total abdominal hysterectomy. Extradural infusion analgesia produced the smallest pain scores from 12 to 24 h after surgery (P < 0.05). More patients in the extradural infusion group were moderately hypoxaemic (SpO2 < 90% > 12 min h-1) after operation, compared with the two other groups (P < 0.05). The group using patient-controlled analgesia received more diamorphine and suffered a greater incidence of emetic sequelae (P < 0.05).


Hypoxaemia and pain relief after upper abdominal surgery: comparison of i.m. and patient-controlled analgesia.

Forty patients recovering from upper abdominal surgery were allocated randomly to receive i.m. morphine 0.15 mg kg-1 as required or patient-controlled analgesia (PCA), with i.v. morphine 1 mg and a 5-min lock out time. Arterial oxygen saturation (SpO2) was measured continuously the night before and for 24 h immediately after surgery. A significantly greater proportion of patients in the PCA group (nine of 19) rated their analgesia as excellent compared with the i.m. group (two of 20) (P < 0.05). There was no significant difference in the incidence of postoperative hypoxaemia in the two treatment groups. Severe postoperative hypoxaemia (SpO2 < 85% for more than 6 min h-1) was seen in three patients receiving i.m. analgesia and one patient in the PCA group.


Effects of isoflurane anaesthesia on the median nerve somatosensory evoked potential in children.

Evoked potentials are used to determine the integrity of neural pathways during neurosurgical and orthopaedic procedures, but the extent to which they may be altered by anaesthetic agents has not been studied systematically in children. In this study we have recorded median nerve somatosensory evoked potentials (mnSSEP) in children during isoflurane anaesthesia to determine if there are changes similar to those seen in adults. We studied 10 patients using standardized anaesthetic and clinical neurophysiological techniques. Control mnSSEP were obtained with 70% nitrous oxide in oxygen and isoflurane was then administered at 0.25, 0.50 and 0.75 MAC. The latencies and amplitudes of the mnSSEP were subjected to repeated measures analysis of the variance (ANOVA) and linear regression. There were statistically significant increases in N20, P22 latencies and central conduction time (P < 0.001) and reductions in amplitude of the N20-P22 complex (P < 0.03) with increasing end-tidal isoflurane concentrations. These results are similar to the findings in adults.


Sequential measurement of the median nerve somatosensory evoked potential during isoflurane anaesthesia in children.

We have used sequential measurements of median nerve somatosensory evoked potentials (mnSSEP) in 10 children to estimate the equilibration time of an inhalation anaesthetic agent between alveolar gas, arterial blood and brain. MnSSEP were obtained sequentially every 90-180 s. After control measurements in the absence of isoflurane, the end-tidal concentration was increased stepwise (0.25, 0.5 and 0.75 MAC). Each isoflurane concentration was maintained for 15 min. The point at which the N20 latency reached stability was determined; the mean time between reaching a stable end-tidal isoflurane concentration and this point varied between 5 min 16 s and 7 min 37 s. This technique may be useful in circumstances in which a "steady state" of anaesthesia is important, such as in the determination of MAC or during intraoperative monitoring of evoked potentials.


Propofol and alfentanil in children: infusion technique and dose requirement for total i.v. anaesthesia.

We estimated the dose of propofol (initial dose followed by a stepped infusion) when given with two different infusion rates of alfentanil for total i.v. anaesthesia in 59 children aged 3-12 yr. Patients in series 1 (four groups) received an alfentanil loading dose of 85 micrograms kg-1 and an infusion of 65 micrograms kg-1 h-1. Patients in series 2 (groups 5 and 6) received an alfentanil loading dose of 65 micrograms kg-1 and infusion of 50 micrograms kg-1 h-1. Parents gave their informed consent. Premedication comprised temazepam 0.3 mg kg-1. Glycopyrronium 5 micrograms kg-1 was administered and anaesthesia induced and maintained with alfentanil (loading dose and infusion) followed by propofol (loading dose and three-stage manual infusion scheme). Suxamethonium 1 mg kg-1 was used to facilitate tracheal intubation and the lungs were ventilated artificially to normocapnia with 30% oxygen in air. Probit analysis was used to determine the dose requirement of propofol. In series 1, the ED50 was 6.0 mg kg-1 h-1 (95% confidence limits 5.5-6.2 mg kg-1 h-1) and ED95 8.6 (6.8-7.8) mg kg-1 h-1. Corresponding values for series 2 were ED50 7.5 (8.0-9.8) mg kg-1 h-1 and ED95 10.5 (9.6-13.1) mg kg-1 h-1.


Pharmacokinetics of lignocaine in children after infiltration for cleft palate surgery.

We have studied the pharmacokinetics of lignocaine in children after local infiltration for cleft palate surgery. After induction of anaesthesia, lignocaine 2.5 mg kg-1 with adrenaline 1:200,000 was injected into the palate. Blood samples were collected before and at 2, 5, 10, 15, 20, 30, 60 and 120 min after infiltration. Plasma concentrations of lignocaine were measured by a gas-liquid chromatographic technique. There were no signs of systemic toxicity on routine monitoring of the patients and the peak plasma concentrations were less than the accepted toxic values. Mean half-life was 72.9 (SEM 9.9) min, similar to that found previously in adults and children. However differences in mean clearance (24.6 (2.04) ml kg-1 min-1) and volume of distribution (0.80 (0.07) litre kg-1) were found between this and previous studies.


Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum.

We have measured concentrations of etomidate and thiopentone in maternal plasma, umbilical venous plasma and colostrum after induction of anaesthesia in 40 patients undergoing Caesarean section. Mean plasma etomidate concentration declined rapidly (1242.0 ng ml-1 at 5 min, 434.0 ng ml-1 at 15 min, 64.2 ng ml-1 at 30 min, 7.0 ng ml-1 at 60 min and undetectable 2 h after the injection). Mean plasma concentrations of thiopentone declined more slowly (6.09 micrograms ml-1 at 5 min, 2.64 micrograms ml-1 at 2 h, 1.35 micrograms ml-1 at 4 h, 0.86 microgram ml-1 at 9 h and 0.59 micrograms ml-1 at 12 h). Mean umbilical venous thiopentone concentration was 4.72 micrograms ml-1, whereas the thiopentone concentration in the maternal sample at 5 min was 6.09 micrograms ml-1, giving an umbilical:maternal vein ratio of 1:1.3. Mean umbilical etomidate concentration was 51.7 ng ml-1 and the corresponding maternal vein sample (5 min) was 1242.0 ng ml-1 (P < 0.001), giving an umbilical:maternal vein ratio of 1:24. Mean concentrations of thiopentone in colostrum were 1.98 micrograms ml-1 at 30 min, 0.91 microgram ml-1 at 4 h and 0.59 microgram ml-1 at 9 h, colostrum:plasma ratios at 4 h and 9 h being 0.67 and 0.68, respectively. Mean concentrations of etomidate in colostrum were 79.3 ng ml-1 at 30 min and 16.3 ng ml-1 at 2 h, being undetectable at 4 h. The colostrum:plasma etomidate concentration ratio was 1.2 at 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)


Spinal anaesthesia for caesarean section: comparison of 22-gauge and 25-gauge Whitacre needles with 26-gauge Quincke needles.

We have studied 150 women undergoing elective Caesarean section under spinal anaesthesia. They were allocated randomly to have a 22-gauge Whitacre, a 25-gauge Whitacre or a 26-gauge Quincke needle inserted into the lumbar subarachnoid space. The groups were compared for ease of insertion, number of attempted needle insertions before identification of cerebrospinal fluid, quality of subsequent analgesia and incidence of postoperative complications. There were differences between groups, but they did not reach statistical significance. Postdural puncture headache (PDPH) was experienced by one mother in the 22-gauge Whitacre group, none in the 25-gauge Whitacre group and five in the 26-gauge Quincke group. Five of the six PDPH occurred after a single successful needle insertion. Seven of the 15 mothers in whom more than two needle insertions were made experienced backache, compared with 12 of the 129 receiving two or less (P < 0.001). We conclude that the use of 22- and 25-gauge Whitacre needles in elective Caesarean section patients is associated with a low incidence of PDPH and that postoperative backache is more likely when more than two attempts are made to insert a spinal needle.


Accuracy of coagulation studies performed on blood samples obtained from arterial cannulae.

We have assessed the accuracy of coagulation studies in blood obtained from intra-arterial cannulae. Paired samples were studied in blood from 39 patients receiving intensive care; one sample was obtained by venepuncture and the other from an intra-arterial cannula after the apparatus deadspace plus 5 ml of blood had been discarded. Activated partial thromboplastin time (APTT) (with thromboplastin routinely used in our laboratory), prothrombin time (PT), thrombin time (TT), fibrinogen and heparin assays were measured on each sample. In 37 sample pairs, APTT was measured also using a different thromboplastin. The median difference between the sample pairs was 5.5 s for APTT (P = 0.032) and 1.0 s (P = 0.048) for TT, the times for arterial cannula samples being longer. There was no significant difference between arterial cannula and venepuncture samples for PT or fibrinogen concentration. Heparin assays revealed heparin contamination in samples obtained from arterial cannulae in 15 of 30 patients not receiving heparin. It is concluded that, when coagulation studies are performed using the techniques used routinely in our laboratory, a blood sample from an arterial cannula may give clinically misleading information because of contamination with small amounts of heparin, and that separate venepuncture is recommended.


Isoflurane does not increase the incidence of intraoperative myocardial ischaemia compared with halothane during vascular surgery.

We have studied the incidence of new intraoperative myocardial ischaemia (IMI), myocardial infarction (MI) and cardiac death (CD) in 500 consecutive patients undergoing elective major non-cardiac vascular surgery. Patients were allocated randomly to receive either halothane (n = 226) or isoflurane (n = 274) as principal anaesthetic agent. Using real-time ST segment trend analysis (leads V5 and II) IMI (halothane 39%, isoflurane 38%), MI (halothane 1.3%, isoflurane 1.5%) and CD (halothane 0.4%, isoflurane 0.7%) did not differ significantly between the two groups. Twenty-three per cent of IMI episodes were related to haemodynamic disturbances, but unrelated to the type of surgery: 148 supra-aortic (IMI = 39%), 244 abdominal aortic (IMI = 41%) and 108 lower extremity revascularizations (IMI = 33%). We conclude that the choice of volatile anaesthetic agent does not influence cardiac morbidity or mortality in this type of patient.


Evaluation of closed loop control of arterial pressure during hypotensive anaesthesia for local resection of intraocular melanoma.

We have studied 20 patients undergoing local resection of intraocular melanoma during hypotensive anaesthesia, allocated randomly to receive either manual control by an experienced anaesthetist or closed-loop computer control of an infusion of a 5:1 mixture of trimetaphan camsylate (TMP) and sodium nitroprusside (SNP). There were no significant differences in the smallest systolic and diastolic arterial pressures obtained, heart rate or infusion requirements between the two groups, but the duration of both the infusion and the operation were significantly longer in the computer-controlled group (P < 0.05). The quality of control of arterial pressure was assessed by the percentage of time spent at pressures greater and less than the prescribed target values, and was satisfactory in both groups during the critical period of profound hypotension. We conclude that the computer-controlled infusion performed satisfactorily during profound hypotension compared with an experienced anaesthetist.


Modulation by carbon dioxide and pH of the contractile responses to potassium and prostaglandin F2 alpha in isolated human pial arteries.

Variation of PCO2 with concomitant changes in extracellular pH (pHo) may modulate cerebrovascular resistance, but the direct actions of carbon dioxide and pHo on human cerebral arteries are unknown. In this study, we have evaluated the effects of different carbon dioxide tensions (2.7, 4.2 and 7.2 kPa) with either fixed (pHo = 7.44) or concomitant changes in pHo, on contractions induced by depolarization (potassium) or receptor stimulation (prostaglandin F2 alpha) in isolated human pial arteries. Isolated changes in PCO2 had no significant effect on either potency (unchanged EC50 value) or the maximum response (Emax) in potassium-contracted arteries. Hypercapnia with uncompensated pHo significantly decreased both EC50 and Emax values, whereas uncompensated hypocapnia significantly increased the EC50 value without any effect on Emax. Concentration-response curves induced by prostaglandin (PG) F2 alpha were shifted significantly to the right (increased EC50 = decreased potency) during both hypo- and hypercapnia, independent of changes in pHo. The maximal responses were enhanced significantly during hypocapnia (Emax = 110 (SEM 2)%), but this enhancement was converted into a slight attenuation when pHo was compensated (Emax = 92 (4)%). Hypercapnia, with or without compensation of pHo, decreased the Emax values to 69 (16)% and 73 (9)%, respectively. We conclude that hypocapnia increases contractility in human pial arteries--an effect which is reversed by compensation of pHo. In contrast, the hypercapnic decrease of PGF2 alpha-induced contractions appears to be independent of pHo. The results confirm a relationship between contractility and pHo, but do not exclude a direct action of carbon dioxide in receptor-stimulated arteries.


Retrograde intubation--a facilitated approach.

The procedure of retrograde tracheal intubation has been facilitated by the use of a multilumen catheter guide. When used as an anterograde guide, it would easily follow the retrograde guide and would direct placement of the tracheal tube atraumatically. A new technique is described that allows stabilization of the anterograde catheter and its insertion deep inside the trachea to prevent dislodgement of the tracheal tube from the laryngeal inlet. This catheter guide may also be used as a conduit for high-frequency jet ventilation with monitoring of the airway pressure, thus providing wider margins of safety in patients with difficult upper airways.


Continuous subarachnoid infusion of 0.125% bupivacaine for analgesia during labour.

We have studied 20 primiparous women requesting pain relief for labour, to determine the feasibility of subarachnoid infusions of bupivacaine for analgesia. A 28-gauge catheter was inserted into the subarachnoid space through a modified 22-gauge Sprotte needle. After a bolus dose of up to 1.5 ml of 0.25% bupivacaine, a continuous infusion of 0.125% bupivacaine was commenced. If analgesia became inadequate, additional 0.5-ml boluses of 0.25% bupivacaine were given (mean number of top-ups 2.8; range 0-6). Persistent perineal pain occurred in four women and this was relieved by 0.5% hyperbaric bupivacaine. Analgesia was good or excellent in 15 of 20 mothers within 10 min and in 19 of 20 within 30 min, and it remained good or excellent throughout labour and delivery. Motor block was complete in three of the women who needed hyperbaric 0.5% bupivacaine. There were no difficulties with insertion of the catheter, no episodes of significant hypotension (systolic arterial pressure less than 100 mm Hg) or postdural puncture headache. Seven mothers delivered their babies vaginally, eight required assistance with forceps and five needed a Caesarean section.


Effect of interpleural morphine on postoperative pain and pulmonary function after thoracotomy.

We have investigated the effect of interpleural morphine on postoperative pain and pulmonary function after thoracotomy. At the end of surgery, an interpleural catheter was inserted in 17 patients and, in a double-blind and randomized manner, either a bolus of morphine 2.5 mg interpleurally (i.p.) and normal saline i.v. (group I) or, as a control for systemic absorption, morphine 2.5 mg i.v. and i.p. saline (group II) was injected. After the initial bolus, a continuous infusion of morphine 0.5 mg h-1 i.p. and saline i.v. (group I) or morphine 0.5 mg i.v. and saline i.p. (group II) was maintained for 24 h. Postoperative pain was assessed by a visual analogue scale, a numerical rating scale and the McGill Pain Questionnaire. Pulmonary function was assessed by spirometry. Supplementary analgesics, side effects, degree of sedation, vital signs and chest tube drainage were recorded. All variables were assessed on the day before surgery and 1, 2, 3, 4, 5, 6 and 24 h and 7 days after surgery. Supplementary morphine was given upon request. There was no significant difference in any pain measure or postoperative pulmonary function variable between the groups. We conclude that, after thoracotomy, interpleural morphine does not provide superior analgesia or improve pulmonary function compared with systemic morphine.


An active heat and moisture exchanger.

We have carried out a laboratory evaluation of an active heat and moisture exchanging filter (aHMEF). The device consists of a conventional heat and moisture exchanging filter (HMEF) with an additional heating element and water supply. It was compared with a standard HMEF using a model lung. The aHMEF with the heating element alone, reduced 2-hourly water loss compared with the HMEF (P < 0.001); with both the heating element and additional water, this was reduced further (P < 0.001). The mean catheter mount temperature with the HMEF and heater was 32.7 (SD 1.8) degrees C and with the complete aHMEF was 34.6 (1.6) degrees C. The maximum temperature with the heating element in use was 37.7 degrees C. We conclude that the aHMEF provided effective, controllable and convenient humidification of inspired gases.


Hepatic function and indocyanine green clearance during and after prolonged anaesthesia with propofol.

We have studied the effects of propofol on hepatic function and clearance of indocyanine green (ICG) in 13 consecutive patients undergoing prolonged plastic and reconstructive surgery. Hepatic function was assessed using serum concentrations of liver-specific glutathione-S-transferase (GST). There were no significant changes in GST activity or plasma clearance of ICG throughout the study.


Apparent pacemaker failure caused by activation of ventricular threshold test by a magnetic instrument mat during general anaesthesia.

A patient with a permanent pacemaker underwent radical neck dissection. After induction of anaesthesia, a magnetic surgical instrument mat was placed over the patient's chest. This caused the pacemaker to go into a threshold test which included a 2.5-s period of asystole. Surgery had to be abandoned temporarily. We suggest that magnetic instrument mats should not be used with pacemaker patients; not all pacemakers are converted to a fixed magnetic rate by application of a magnet. The anaesthetist should check to see if the patient has a pacemaker with a threshold test and, if possible, this should be rendered inactive.


Extradural abscess complicating extradural anaesthesia for caesarean section.

Extradural abscess has been described infrequently as a complication of extradural anaesthesia and analgesia. We describe an abscess that developed 5 days after operation in a patient who had extradural anaesthesia for Caesarean section and postoperative analgesia, and review the literature on extradural abscess complicating extradural catheterization, including a discussion on pathogenesis, clinical presentation, diagnosis and management. There have now been 16 reported cases of extradural catheter-related extradural abscess. Only one previous case has been in obstetric practice, despite the widespread use of these techniques in this specialty. A disproportionate number of cases have involved thoracic catheters. Duration of catheterization ranged from 40 h to 6 weeks, the majority of catheters being in place for 5 days or less. The time from catheter placement to development of symptoms ranged from 72 h to 5 months. The causative organism was isolated in 11 cases: Staphylococcus aureus was identified in nine (82%) and Staphylococcus epidermidis in two (18%). Outcome was reported in 15 cases, of which seven (47%) had a full or near full recovery and eight (53%) had a persistent neurological deficit. One case was managed successfully without surgery. Fifty percent of all cases have been reported in the past 5 years. With the increasing use of extradural techniques for anaesthesia and analgesia, this serious complication may be seen more frequently in the future.


General anaesthesia and the hypereosinophilic syndrome: severe postoperative complications in two patients.

Two patients with markedly increased eosinophil counts developed severe postoperative complications after general anaesthesia. One patient suffered life-threatening Adult Respiratory Distress Syndrome (ARDS), while the other presented with a coagulopathy and less severe respiratory problems. The hypereosinophilic syndrome is described and the possibility of a role of eosinophils in the pathogenesis of tissue injury is discussed. These cases suggest that, in patients with marked eosinophilia requiring general anaesthesia, perioperative steroid cover is advisable. This may reduce or prevent serious lung damage and other complications.


[The incidence and clinical significance of the echocardiographic finding of false chordae tendineae].

The presence of false tendons (FT) with M-mode and 2-D echocardiography in a consecutive series of 916 patients (520 men--396 women) with a wide age range (9-83 y) was investigated, and a possible correlation with heart systolic murmurs and/or heart arrhythmias evaluated. The problems that FT cause in differential diagnosis with other intraventricular structures were also considered. FT were observed in 53 subjects (5.8%), 30 men--23 women, and in an additional 51 cases (96%) in the left ventricular cavity. A clear prevalence of FT was observed during childhood and adolescence (26.1%), with the preferential location at the top of the ventricular chamber. No relevant correlation between FT and heart systolic murmurs and/or cardiac rhythm disorders was found. Although our results show that FT constitute an occasional finding, with no anatomic or functional relevance, they should always be held in due consideration in case of diagnostic uncertainty with other pathological structures, in particular intracavitary thrombi.


[Nonischemic changes of the ST segment in dynamic electrocardiography].

Ambulatory ECG monitoring has become increasingly important in the diagnostic workup of patients investigated for chest pain and in the evaluation of patients with known ischemic heart disease. Following the demonstration of ischemic episodes not associated with anginal symptoms, the diagnosis of myocardial ischemia is based solely on the detection of ST segment shifts; however several conditions associated with non-ischemic ST segment changes during ambulatory ECG monitoring might potentially be misleading. These conditions include: 1) ST segment changes in the normal population: it is a rare finding in specifically designed studies that however are probably affected by a "pretest referral bias"; caution is therefore suggested in diagnosing ischemia when episodes of ST segment depression are mild (< 2 mm) and occur at high heart rates (> 120 beats/min); 2) postural changes, usually easily recognized by the typical "square" pattern of the ST segment trend; 3) ST segment changes related to respiratory manoeuvres, quite rare and usually mild; 4) ST segment changes due to drugs; 5) ST segment changes caused by rhythm and conduction disturbances. Lastly the significance of ST segment changes in patients with angina and normal coronary arteries is discussed, following recent observations of reduced coronary flow reserve and/or abnormal myocardial metabolism in a sizable proportion of these patients.


[Cryptococcosis in a female patient with angioimmunoblastic lymphadenopathy and dysproteinemia].

A case of a 72-year-old woman affected by angioimmunoblastic lymphadenopathy with dysproteinemia is described. She was admitted to the hospital for serious cutaneous lesions and dementia. The patient had been treated with corticosteroids for the previous two years. Cryptococcosis was diagnosed by cutaneous biopsy. Antimycotic therapy together with corticosteroid withdrawal cured the cutaneous lesions and improved her psychiatric symptoms.


[Familial Mediterranean fever: a report of 2 cases of Italian origin].

Familial Mediterranean fever is an inherited disease, occurring almost exclusively in Arabs, Jews and Turks. Cases are very rarely described in the USA, USSR, France, and patients are all natives to the Mediterranean area. This paper describes two cases of familial Mediterranean fever in brothers native to Campania, Italy. Both had complained of repeated episodes of fever, with acute abdomen, thoracalgia and arthralgia since the age of about 20. One of them had had pleuritis when he was 6 years old. In the period preceding our first observation, both underwent laparotomy to evaluate abdominal symptoms, with negative results. After ruling out other diseases with similar signs and symptoms, we raised the hypothesis of familial Mediterranean fever, despite the fact that the literature has described very few Italian natives affected by this disease. The diagnostic hypothesis was confirmed by the positivity of the metaraminol provocation test. At the same time we evaluated the presence of amyloidosis by rectal biopsy, with negative results. Treatment with colchicine 1 mg/day per os was established. Dramatic improvement of the symptoms was observed in both patients. The present paper stresses the importance of familial Mediterranean fever, its correct diagnosis in Italy and the fundamental role played by the metaraminol provocation test as a determinant diagnostic tool. It allows establishment of appropriate treatment as soon as possible, so that renal amyloidosis, the most severe complication and major prognostic determinant of familial Mediterranean fever, can be prevented. Inappropriate, useless and potentially harmful surgical diagnostic procedures are also avoided.


[Adherence to dietetic treatment, the nutritional metabolic status and the progression of chronic kidney failure].

Effects of two protein restricted diets on dietary compliance, nutritional and metabolic state, and progression of chronic renal failure (CRF) were investigated. Twenty-one patients with CRF were randomly assigned to either a conventional low protein diet (0.6 g of protein/kg b.w./day) or to a very low protein diet, providing 0.4 g of protein/kg b.w./day, supplemented with a mixture of essential amino acids which contained HIS, TYR and a high proportion of branched chain amino acids. Nutrition, assessed by body weight, anthropometry, serum protein levels and nitrogen balance studies, was maintained in all patients. Some metabolic abnormalities of CRF (i.e., secondary hyperparathyroidism, glucose intolerance) improved in both groups. The supplemented diet provided better adherence to protein prescription, corrected the depletion of VAL and LEU in muscle and was more effective than conventional diet in slowing the rate of progression of CFR.


[Alpha-interferon therapy: an echographic study of left ventricular function and a clinical assessment of cardiovascular complications].

Many side-effects of alpha interferon (alpha-I) therapy have occurred as a result of its widespread clinical applications. The hypothesis of alpha-I related cardiomyopathy is particularly interesting. Our study involved echocardiographic evaluation of left ventricular function and cardiovascular complications in 35 patients with chronic hepatitis treated with alpha-I at 20 MU/week for an average of 10.8 months. The results were compared with those of a control group. Of the values studied, only Max E V and the E/A ratio were statistically significant. No cardiovascular side-effects were found.


[The neuroendocrine aspects of chronic alcoholism: the effect of alcohol intake and its withdrawal].

Neuroendocrine dysfunctions, in part similar to those found in depression, are present in chronic alcoholism. The aim of this investigation was to evaluate the effects of chronic alcohol intake on cortisol secretion in basal conditions, after dexamethasone (DXT) suppression or corticotropin (ACTH) stimulation in 10 alcoholic men, during active drinking and after two weeks of alcohol withdrawal. The 24-hour, day- and night-time urinary cortisol and melatonin levels, and the effects of thyrotropin releasing hormone (TRH) on thyrotropin (TSH) and prolactin (PRL) secretions were studied in the same subjects. The data were correlated to the scores obtained by the Hamilton Rating Scale for depression and compared to those found in healthy subjects. Increased cortisol levels and the lack of DXT suppression of cortisol secretion are considered to be alcohol-dependent inasmuch as they disappear in most patients after alcohol withdrawal. The cortisol response to ACTH 1-24 infusion measured before and after alcohol withdrawal was similar in the patients we studied; moreover no significant difference was found between patients and controls. The increment of urine free cortisol levels in active alcoholics was not statistically significant. Urine cortisol levels became similar to those of the control subjects after alcohol withdrawal. The increased diurnal values of urine melatonin and the inversion of the physiological ratio between nocturnal and diurnal levels observed during alcohol intake became normal upon alcohol withdrawal. The TSH and PRL responses after the administration of 50 or 200 micrograms TRH were higher in alcoholics than in controls, while a blunted response is known to occur in depression.


[The current outlook in the therapy of autoimmune diseases].

Recent advances in immunology and molecular biology have contributed to a much greater understanding of the pathogenetic mechanisms of the autoimmune diseases and thus to the development of new rationally-based therapies. Most of the immunosuppressive agents that have been tried in autoimmune disease patients nonspecifically suppress the immune response, often causing various side effects. Autoimmune diseases result from the activation of self-reactive T cells that recognize autoantigens or foreign antigens cross-reactive with an autoantigen coupled with major histocompatibility complex (MHC) products on an antigen presenting cell. It appears possible to modulate T cell activation by interfering with the interaction between T cell receptor and the peptide-MHC molecule complex. A number of sites are potential targets for immunologic intervention, such as MHC molecules, T cell receptor, CD4 and CD3 molecules, adhesion molecules, cytokines and cytokine receptors. In the present review the most important new therapeutic approaches to autoimmune conditions, which appear to be more selective in overcoming the limitations of non-specific treatments, are summarized. They include monoclonal antibodies, cytokines and cytokine-inhibitors, peptides interacting with MHC molecules and T cell vaccination.


Introducing NMDA antagonists into clinical practice: why head injury trials?

1. Head injury is the major cause of death and severe disability in young adults. Evidence from clinical studies shows ischaemic brain damage to be the major determinant of bad outcome, and that a proportion of this (perhaps up to 40%) is delayed, thus offering an opportunity for 'prophylactic' therapy. 2. Laboratory studies in several relevant animal models of human head injury (fluid percussion, subdural haematoma, and focal ischaemia by middle cerebral occlusion) indicate that excitatory amino acids are important mediators of brain damage. Pretreatment with NMDA antagonists has shown that the extent of ischaemic damage may be dramatically reduced in these models (68% reduction in the cat MCA occlusion model, 54% in the rat subdural haematoma model). 3. Trials of NMDA antagonists in human head injury are therefore strongly indicated.


The effects of an oral thromboxane TP receptor antagonist BAY u 3405, on prostaglandin D2- and histamine-induced bronchoconstriction in asthma, and relationship to plasma drug concentrations.

1. The potent bronchoconstrictors prostaglandin (PG) D2, PG F2 alpha and thromboxane A2 are thought to have a role in the pathogenesis of asthma, mediated via the thromboxane (TP) receptor. 2. BAY u 3405 is a new potent selective competitive TP receptor antagonist. 3. The effect of single oral doses of 20 mg and 50 mg BAY u 3405 was examined against histamine and PG D2 bronchial provocation at 90 min after drug ingestion and, for the 20 mg dose alone, at 60 min after ingestion, in randomised, double-blind placebo controlled crossover studies. A time course study was performed with the 20 mg dose. 4. BAY u 3405 protected against PG D2 bronchial provocation. The 20 mg dose increased the amount of PG D2 required to produce a fall of 20% in the forced expiratory volume in 1 s by 6-fold and 16-fold at 60 min and 90 min after ingestion respectively, and the 50 mg dose by 14-fold at 90 min after ingestion. 5. The specificity of the drug was confirmed in vivo in that there was no significant protection against histamine bronchial provocation at either dose or at either time point. 6. The time course study showed significant protection against PG D2 bronchial provocation at 1 h and at 3 h after a single 20 mg oral dose. 7. There was no correlation between subjects in plasma BAY u 3405 concentration and drug effect. Within the subjects performing the time course study there was a strong correlation in time between drug effect and plasma BAY u 3405 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of leukotrienes C4 and D4 on human isolated saphenous veins.

1. Vascular injury during the intra-operative procedures of bypass surgery may be the initiating event in the gradual deterioration in the patency of the graft. Adhesion of leukocytes to the vascular endothelium frequently accompanies preparation and insertion of the graft. However, little is known about the effects of vasoactive substances released from leukocytes on vein graft performance. 2. To determine whether leukotrienes are capable of affecting the tone of blood vessels used as coronary artery bypass grafts we studied the human saphenous vein as intact rings using an isolated organ bath technique. 3. LTC4 and LTD4 caused weak endothelium-dependent relaxations at lower concentrations (1 pM to 1 nM) and powerful endothelium-independent contractions at higher concentrations (3 nM to 0.1 microM). The maximum responses to LTC4 and LTD4 for relaxations were 21.1 +/- 4.8% and 28.6 +/- 3.4% (% of noradrenaline induced tone) respectively and 64.6 +/- 9.9% and 59.1 +/- 7.9% (% response to KCl) respectively for contractions. 4. The inhibitor of nitric oxide formation, L-NG-monomethyl L-arginine, prevented the relaxations to LTD4, but not LTC4 and unmasked endothelium-dependent contractions to LTD4 (32.9 +/- 11.3%). NG-monomethyl L-arginine had no effect on the contractions produced by LTC4 or LTD4. 5. Indomethacin augmented relaxations and contractions of saphenous vein to LTC4 from 22.5 +/- 5.6 to 40.02 +/- 8.7 (P < 0.05) and 48.8 +/- 5.5% to 74.7 +/- 7.6% (P < 0.01) respectively. LTD4 responses were not affected by indomethacin treatment. 6. In conclusion, leukotrienes mediate biphasic responses in the human saphenous vein.(ABSTRACT TRUNCATED AT 250 WORDS)


7-Alkoxyquinoline O-dealkylation by microsomes from human liver and placenta.

1. The O-dealkylation of seven 7-alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7-alkoxyquinoline metabolism was studied. 2. None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3. Maternal cigarette smoking induced the O-dealkylation of all of the 7-alkoxyquinoline derivatives, being greatest for 7-butoxy- and 7-benzyloxyquinoline. 4. Placental 7-alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1-7-1 raised against 3-methylcholanthrene-induced rat liver P450. 5. None of the 7-alkoxyquinoline O-dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta.


Attitudes to adverse drug reaction reporting in the Northern Region.

1. The attitudes and knowledge of doctors in the Northern Region to reporting of adverse drug reactions were assessed using a postal questionnaire to all doctors in two, previously identified, high reporting and two low reporting health districts. Comparisons were made of the attitudes and knowledge within professional groups (GPs, Consultants and Junior Hospital Doctors), and between the amalgamated doctor groups. 2. 1181 of 1600 doctors (74%) responded. Despite being selected on the basis of previous adverse drug reaction reporting patterns, GPs and consultants from high and low reporting districts perceived they had sent a similar number of ADR reports, and there were few differences in opinion and attitude within these two groups. 3. Most differences within doctor groups were found for junior doctors, with those from low reporting districts indicating they had sent significantly less yellow cards than those in high reporting districts. There were also significant differences in the estimates junior doctors made with a frequency of adverse drug reactions, the existing documentation on adverse drug reactions, and the purposes of the adverse reaction scheme. 4. General Practitioners in low reporting areas stated they wrote more prescriptions (P < 0.02), consultants spent more time in clinical contact (P < 0.01) and junior doctors did both (P < 0.01), all of which suggest different workloads may effect reporting of adverse drug reactions. 5. When given clinical examples, or asked about the CSMs black triangle scheme, all doctor groups performed poorly. 6. The number of reports stated as being sent increased with time from qualification for 10 years, then seemed to plateau.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduction of plasma cholesterol by lovastatin normalizes erythrocyte membrane fluidity in patients with severe hypercholesterolaemia.

The effect of lovastatin on erythrocyte membrane composition and fluidity was investigated in eight patients with severe hypercholesterolaemia (mean LDL-cholesterol of 7.2 mmol l-1). Lovastatin was administered at a dosage of 40-80 mg for 20 weeks and was discontinued for 5 weeks thereafter. Parallel to a 47% fall in plasma LDL cholesterol, there was a significant reduction (P < 0.01) in erythrocyte membrane cholesterol:phospholipid molar ratio, while erythrocyte membrane fluidity assessed by diphenylhexatriene (DPH) fluorescence polarization increased significantly (P < 0.01). Discontinuation of lovastatin resulted in the reversal of erythrocyte membrane composition and fluidity to pre-treatment values.


Plasma morphine-3-glucuronide, morphine-6-glucuronide and morphine concentrations in patients receiving long-term epidural morphine.

Plasma morphine concentrations were measured in five cancer patients receiving long-term epidural morphine administration. Peak concentrations were observed within 1 h of dosage and concentrations then declined biexponentially. Plasma morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations were measured in two patients and plasma M3G concentrations were observed to be much higher than plasma M6G and morphine concentrations. Peak plasma M6G concentrations occurred within 1.0 h of dosing and plasma M6G concentrations then remained higher than plasma morphine concentrations.


Morphine metabolism in neonates and infants.

The metabolism of morphine was studied in seven fullterm neonates and five infants receiving a continuous infusion of morphine. All the patients had detectable plasma concentrations of morphine 3-glucuronide (M3G) and 10 had detectable concentrations of morphine 6-glucuronide (M6G). The mean plasma clearance of morphine was 20.1 ml min-1 kg-1 in neonates and 23.4 ml min-1 kg-1 in the group as a whole. The M3G/morphine ratio (7.3) was higher than that previously reported for preterm neonates (5.0) but lower than that reported for children (23.9).


Stereoselective inhibition of renal organic cation transport in human kidney.

Amantadine was found to be concentrated by human cortical slices, with apparent Km and Vmax values of 187 +/- 11 microM and 1.37 +/- 0.28 nmol mg-1 min-1 respectively (mean +/- s.e. mean, n = 4). Addition of quinine (8S, 9R-(-)-isomer) or quinidine (8R, 9S-(+)-isomer) competitively inhibited this accumulation (apparent Ki values of 261 +/- 44 (n = 4) and 586 +/- 68 microM (n = 3), respectively). The stereoselectivity of this inhibition is the reverse of that seen with respect to the renal clearances of the diastereoisomers.


[Liver transplantation without clamping the vena cava inferior].

An original technique of orthotopic liver transplantation with preservation of the recipient's entire inferior vena cava and side-to-side caval anastomosis is described. The procedure was used in 21 consecutive patients. It has permitted to avoid vena cava occlusion and the need for venous bypass. No consequences on caval flow were observed during the anhepatic phase. Such technique avoids retrocaval dissection and requires only one caval anastomosis, reducing the duration of the anhepatic phase.


[PTFE in reconstructive surgery on the face].

The employment of synthetic materials instead of autologous tissues (cartilaginous, adipose tissue, etc.) is already well codified and widely spread: the only restraint to their use is represented by biocompatibility which is not always satisfactory. Prosthesis should be clinically inert and inalterable with time, easy to sterilize, intraoperatively mouldable, and, from the aesthetic point of view, unrecognizable at touch. Since PTFE is widely used in general surgery (vascular prosthesis, aortobifemoral bypass, ect.) we have employed it in plastic surgery obtaining good results in the correction of malar depressions, and in harmonizing the final result of a rhinoplasty or of a labial plasty. All patients showed to well tolerate the material employed without any evident inflammatory reaction and with stable results at long-term follow-up.


[A case of so-called Poland's syndrome].

Pathogenesis, morphology and different associated abnormalities in the so-called Poland syndrome are considered. The surgical treatment adopted in the case recently observed is discussed. In most cases an isolated muscular and breast hypoplasia or aplasia is present so that surgery has the only intent to solve the esthetic problem.


[Multiple hamartomas of the bile ducts (MBDH) or von Meyenburg's complex].

Multiple bile duct hamartomatosis of the liver or so-called von Meyenburg's syndrome, is an infrequent disease related to a dysembryogenic error. The authors discuss clinical features, diagnostic methods and possible related pathologies. Data reported in the literature are also received.


[Leiomyosarcomas of the stomach: a report of 3 clinical cases and a review of the literature].

Three consecutive malignant smooth-muscle gastric tumor cases are reported. Digestive endoscopy allowed a correct diagnosis in 2 out of 3 cases, when neoplasias were ulcerated, enabling a deep endoscopic biopsy. On the contrary, in the third case the endoscopic diagnosis was a benign leiomyoma and the endoscopic biopsies were completely negative. Even CT scan was not able to reveal the malignant nature of the disease in this patient. Surgical procedures performed were: polar superior gastric resection, Billroth I partial gastric resection and extended total gastrectomy. In one patient, regional lymph nodes were positive for metastases. The patient who died at 6 months from surgery had a large (approximately 12 cm) neoplasia of the gastric fundus.


[Carcinomas of the right colon. A review of 60 consecutive cases].

Sixty consecutive cases of tumor of the right colon operated upon between 1981 and 1991 are reviewed. Age and sex distribution, clinical findings, preoperative diagnostics and system used staging, TNM classification, surgical management, operative mortality, follow up and survival were analyzed. Results are discussed and compared with published data. In the second of the two 5-year period considered an increased incidence of right-sided carcinoma compared with tumors of the left colon and rectum was observed. According to the TNM classification, more than 50% of patients were in stage III. Operative mortality was 5%. The overall 5-year survival rate was 58%, while the survival rate of patients treated with radical intent was 70%.


[Conservative elective surgery in kidney neoplasms].

After the good results of "necessary" conservative surgery in the treatment of kidney neoplasms (bilateral neoplasms, congenital, acquired or functional solitary kidney), conservative surgery itself has been employed as elective treatment in selected cases presenting without the overmentioned problems. The authors report two cases of elective conservative surgery in kidney neoplasm with good results after 18 and 24 months.


[Bilateral breast tumors].

From a retrospective analysis of 181 cases observed in a ten-year period (1980-1990), the authors registered a frequency of bilateral breast cancer comparable to that reported in the literature (1-12%). Early diagnosis is the only factor able to modify positively the prognosis, through an accurate follow up, based on blood and X-ray tests (low-density mammography).


[The treatment of recurrent inguinal hernias by using Marlex mesh preperitoneally].

Several techniques are utilized in the treatment of inguinal hernia: each type of repair offers advantages, but a variable number of recurrences occurs regardless of the hernioplasty technique used. Treatment of hernial recurrence is a troublesome goal for surgeons. Nowadays, the use of prosthetic materials with a posterior surgical approach simplifies and resolves most of the problems encountered in the past. The authors report their experience with the use of Marlex mesh for hernia repair through a preperitoneal approach pointing out the advantages of such prosthetic material and of the surgical access as well. Finally, the importance of patients selection is stressed.


[Resection of the sigmoid via laparoscopy: an experimental study of its feasibility].

The authors describe an experimental laparoscopic sigmoid colon resection performed in the porcine model. The operation begins with the introduction of the laparoscope via an umbilical trocar. Five other trocars are then placed allowing different maneuvers. The sigmoid colon is grasped in order to gain access to its mesenteric vessels which are clipped and divided, carrying out the dissection of the entire sigmoid colon. Two modified Endo-GIA are then fired both cranially and caudally, in order to obtain a closed sigmoid specimen and to maintain patent the lumen of the descending colon and rectum. The sigmoid is removed transanally. A P-CEEA stapler is introduced via the rectum and its detached anvil is put into the lumen of the descending colon. A purse-string is applied and closed around the anvil rod. The P-CEEA is retracted, and the rectal stump closed with another Endo-GIA. After reintroducing the trocar-loaded stapler, the trocar is advanced through the suture line of the rectum and removed via a port. The stapler is then reassembled, fired and extracted through the anus. Taking into account the oncologic criteria, we think that this mini-invasive technique could be applied, after an adequate training period on the animal model, to humans also.


Hypothesis: new concepts concerning the pathophysiology of the sudden infant death syndrome due to magnesium deficiency shock.

There appear to be many contributing factors to sudden infant death syndrome (SIDS). One final common pathway that may explain some cases of SIDS is presented as a hypothesis: SIDS occurs as a shock-like event in a stressed infant with congenital or acquired magnesium deficiency with respect to calcium, or with genetically determined high magnesium requirements. Increased calcium and stress-related catecholamines favour platelet aggregation and release of mediators, chief of which appears to be thromboxane A2 (TXA2). TXA2, a major vasoconstrictor, bronchoconstrictor, and platelet aggregator is relatively unopposed during shock by prostacyclin, a vasodilator, bronchodilator, and platelet disaggregator which normally counterbalances its effects. The shock episode is self-limited. Infants who recover have suffered an apparent life threatening event (ALTE); those who die have insufficient pathology to explain the cause of death; the diagnosis is SIDS.


Serum and mononuclear cell potassium, magnesium, sodium and calcium in pregnancy and labour and their relation to uterine muscle contraction.

Thirty women in their third trimester of pregnancy (37-42 weeks), 40 women during and 72 h after labour and 18 non-pregnant controls were studied for changes in serum and mononuclear cell cation content, and their relationship to cervical effacement and intensity of pain as measured by plasma beta endorphin concentrations during labour. Serum magnesium fell from 0.95 +/- 0.01 (mean +/- SEM) to 0.84 +/- 0.02 mmol/litre at late pregnancy and further to 0.76 +/- 0.01 during labour (P < 0.001); serum potassium fell from 4.25 +/- 0.05 to 3.79 +/- 0.06 mmol/litre (P < 0.0001) during labour; and serum calcium fell from 2.40 +/- 0.02 to 2.28 +/- 0.01 mmol/litre at late pregnancy (P < 0.001) and further to 2.25 +/- 0.02 mmol/litre during labour (P < 0.001). Mononuclear cell magnesium content rose from 4.5 +/- 0.3 to 5.6 +/- 0.04 fmol/cell (P < 0.02); potassium content rose from 37.7 +/- 2.0 to 50.9 +/- 3.0 fmol/cell (P < 0.001); and calcium content rose from 4.4 +/- 0.4 to 7.6 +/- 1.1 fmol/cell (P < 0.105). On the other hand, mononuclear cell sodium content fell from 7.2 +/- 0.5 to 3.8 +/- 0.3 fmol/cell (P < 0.001). Plasma beta endorphin concentrations increased with increasing degrees of effacement, as did intracellular Na, whereas intracellular Mg and K showed an inverse trend. A significant correlation was found between intracellular cation and beta endorphin levels (r = -0.98, Mg; -0.99, K; 0.83, Na). These changes are probably due either to intercompartmental cation shifts or possibly to endometrial ischaemia and damage during labour.


Oral magnesium supplementation improves fetal circulation.

It is well known that pregnancy is a condition in which plasma magnesium falls because of accumulation of the ion in the placenta and fetus. Magnesium (Mg) is therefore widely given as a supplement during pregnancy, particularly in cases of preterm labour. In our experience, the combination of oral Mg (magnesium pyrrolidone carboxylic acid) at a dose of 360 mg/day with conventional ritodrine treatment allows a reduction in ritodrine dosage, accompanied by a significant reduction in side effects. We therefore evaluated changes in fetal blood flow, using pulsed Doppler, in women submitted to combined magnesium and ritodrine treatment compared to those treated with ritodrine plus placebo. The Mg-treated group showed a decrease in vessel resistance both in the umbilical artery and in the fetal middle cerebral artery, indicating that fetal vasculature is sensitive to exogenous Mg. Measurement of plasma and mononuclear cell Mg showed an intracellular increase in the cation of about 10 per cent. We conclude that oral magnesium supplementation in pregnancy is safe and that it has a positive effect on the fetal circulation.


Magnesium and obesity: influence of gender, glucose tolerance, and body fat distribution on circulating magnesium concentrations.

Obesity is characterized by a high risk for glucose intolerance and cardiovascular disease. Since magnesium deficiency or depletion have often been associated with both pathologies, is of interest to study magnesium status in severely obese subjects before any form of treatment. Negative magnesium balances have been described in overweight persons submitted to total starvation, hypocaloric diets, and obesity surgery. For this reason 80 non-diabetic obese men and 118 age-matched obese women were studied. Serum and erythrocyte magnesium concentrations were significantly higher in the male population but the mean values were not suggestive of a magnesium deficit before any form of treatment was started. Since metabolic abnormalities and cardiovascular risk are greater in patients with upper body fat distribution (UBFD) both sexes were subdivided according to "waist-to-hip" circumference ratio. No difference could be shown in the obese men but in women, UBFD subjects showed higher basal insulin levels and increased erythrocyte magnesium concentration as compared to those with classical gynoid fat distribution. A 75 g oral glucose tolerance test enabled the subjects to be subdivided into those with normal or impaired glucose tolerance (IGT). The IGT group in both sexes was older and more obese. Mean values of serum magnesium and erythrocyte magnesium were not decreased despite the more pronounced insulin resistance in the IGT group. However a significant negative correlation was found between fasting blood sugar/insulinaemia and erythrocyte magnesium, showing that this middle-aged obese population can maintain normal circulating levels of magnesium, in contrast to type II diabetics or older subjects where for other reasons (urinary losses or decreased intake) magnesium status is interfered with.


Serum and erythrocyte magnesium concentrations in solid tumours: relationship with stage of malignancy.

Magnesaemia is often decreased in solid tumours, but magnesium (Mg) is mainly an intracellular cation and serum levels do not reflect actual body stores. In this study serum Mg (SMg) and erythrocyte Mg (EMg) concentrations were measured in 40 healthy controls and in 108 patients affected by various types of tumour (50 lung cancers, 25 breast cancers, 18 ovarian cancers, and 15 oropharyngeal and hypopharyngeal cancers). EMg was higher (P < 0.05) and SMg lower P < 0.001) in neoplastic patients than in controls. All tumour types behaved in the same way, though in the lung cancer group the increase in EMg did not reach statistical significance in comparison with the control group (P = 0.05). The extent to which EMg was increased and SMg decreased was positively correlated with the advancement in the stage of malignancy. These results suggest that in neoplastic disease Mg requirement is not only increased in tumour tissue, but also in erythrocytes. The increase in EMg may derive from a change in the red blood cell membrane, facilitating intracellular concentration of magnesium for transport to the tumour. The concomitant decrease in SMg may be the consequence of the enhanced erythrocyte uptake of magnesium from the extracellular circulating pool.