Wound colonisation following cardiac surgery. Reduction by adjuvant use of preincisional, presternal antibiotic infiltration: a double blind prospective randomised study

In a double blind, prospective, randomised study of 100 patients undergoing elective cardiac surgery, a significant (p less than 0.01) reduction in wound colonisation, defined as positive culture of any wound discharge irrespective of wound appearance, occurred in those receiving preincisional presternal antibiotic infiltration (2%) as compared to a control group who received a similar volume of normal saline by the same route (24%). Both groups received, in addition, the same conventional intravenous regimen of broad spectrum antibiotic. A comparable concurrent group of patients, not entered into the study, demonstrated a wound colonisation rate similar to the trial control group (22%), thus excluding an adverse bias from the control saline infiltration. Analysis of control cases demonstrated a significant (p less than 0.001) discriminant effect in the degree of preoperative haemodilution with haematocrit falling on bypass by a mean of 25% in those who developed wound colonisation as compared to 13% in those who did not.     

Urinary excretion of 3-methylhistidine, creatinine and total nitrogen by Kenyan children during acute measles and after recovery

The urinary excretion of 3-methylhistidine (3MH), creatinine and total nitrogen was measured during the course of energy balance studies on 20 black Kenyan children. Studies were carried out over 24 h during an acute attack of measles with a second (control) study after recovery, and complete urinary collections were obtained on 14 ill and 18 recovered children. The nutritional status was assessed by anthropometry, and energy intake was determined by duplicate diet analysis. Twelve out of 13 acutely ill and 6 out of 17 recovered children were in negative energy balance. No effect on the rate of excretion of 3MH or of creatinine attributable to differences in nutritional status, of energy intake or to infection was observed. The linear relationship between the excretion rate of all three metabolites and body weight which was observed in recovered children was absent during acute infection. Nitrogen excretion was correlated (P less than 0.05) with the level of energy intake. The linear relationship between the rate of excretion of 3MH and creatinine and of 3MH and nitrogen was significantly closer in recovered than in ill children. The simultaneous effects of infection, underfeeding (and oliguria) on the rate of excretion of protein metabolites may be complex and contradictory. Our results suggest that the excretion of 3MH, creatinine and nitrogen is sustained during infection accompanied by negative energy balance. Disruption during infection of the relationship between the excretion of all three metabolites and body weight, and between 3MH and the other two metabolites suggests perturbation in protein metabolism at this time.     

Maternal fish oil supplementation in pregnancy modifies neonatal leukotriene production by cord-blood-derived neutrophils

Fish oil supplementation has been shown to reduce neutrophil production of inflammatory LTB4 (leukotriene B4) in adults. The present study is the first to examine the effects on neonatal neutrophil function following supplementation in pregnancy. Pregnant women with allergic disease (n=98) were randomized to receive either fish oil [3.7 g of n-3 long-chain PUFAs (polyunsaturated fatty acids)/day] or a placebo supplement for the final 20 weeks of pregnancy. Leukotriene production by neonatal neutrophils was measured after stimulation with the calcium ionophore A23187. This was examined in relation to supplementation, cell membrane fatty acid levels and mononuclear cytokine production. Neutrophil LTB4 production was significantly reduced in neonates whose mothers had received fish oil in pregnancy. This was most evident for isomer 2 of LTB4 (P=0.031), although this was also observed for total LTB4 (P=0.051) and isomer 1 (P=0.088). There was also a trend for lower production of other PUFA metabolites, namely 5-HETE (5-hydroxyeicosatetraenoic acid; P=0.054) in the fish oil group. Accordingly, LTB4 levels were inversely related to membrane n-3 PUFA levels. Less inflammatory products (LTB5) were only produced at very low levels, although there was a trend for higher levels of this metabolite in the fish oil group. Consistent with this, LTB5 levels were positively correlated with n-3 PUFA membrane levels, particularly EPA (eicosapentanoic acid) and negatively correlated with n-6 PUFAs. Neonates with lower neutrophil LTB4 production also had lower production of pro-inflammatory IL (interleukin)-6 responses (r=0.35, P=0.005) and regulatory IL-10 responses (r=0.37, P=0.003) by LPS (lipopolysaccharide)-stimulated neonatal mononuclear cells. In conclusion, maternal dietary changes can modify neonatal neutrophil function. This has implications for the early immune programming, which can be influenced by the inflammatory milieu of local tissues during initial antigen encounter. It also provides evidence of another pathway through which long-chain PUFAs status can influence early immune development.     

Acute and chronic effects of once-daily isosorbide-5-mononitrate on the exercise capacity of patients with angina pectoris treated with a beta-blocking drug.

Forty-four patients with stable effort angina pectoris were included in a double-blind, randomised, placebo-controlled, parallel group study to compare the effect of two slow-release forms of isosorbide-5-mononitrate ('Ismo-Retard' 40 mg and 'Imdur' 60 mg) on exercise capacity when given as an adjunctive treatment to beta adrenoreceptor blocking therapy. In a symptom-limited exercise test performed three hours after the first dose, Ismo-retard increased the total duration of exercise by 92 seconds (confidence interval (CI) 5.1-116.9) p less than 0.006, and the time of onset to anginal pain by 117 seconds (CI 27.8, 156.1) p less than 0.004. A similar improvement in total duration of exercise (by 87 seconds) was noted three hours following 15 consecutive once-daily doses (CI 16.8-128) p less than 0.02, and in the time of onset to anginal pain by 101 seconds (CI 19.8-139.6) p less than 0.01. For Imdur the corresponding results were 53 seconds (CI 12.7-56.3), 84 seconds (CI 15.4-103.7), p less than .02, 54 seconds (CI 1.4-78.4) and 85 seconds (CI 6.9-120.5) respectively. These results would suggest that both active treatments were effective anti-anginal agents.     

How do homeopaths make decisions? An exploratory study of inter-rater reliability and intuition in the decision making process

The validity of clinical decision making in homeopathy is largely unexplored and little is understood about the process or its reliability. This exploratory study investigated, in the context of a questionnaire based re-proving of Belladonna 30c, the extent to which decisions are based on clinical facts or intuition and how reliable decisions are. Three experienced, independent homeopathic clinicians/proving researchers rated the symptom diaries of the 206 subjects taking part. They reported their proving decision (ie positive proving response, no proving response or undecided) based on the total symptom profiles and rated (on a scale of 0-10) their use of clinical facts or intuition. Keynote symptoms and overall confidence scores were also reported. The level of agreement between raters was generally poor (weighted kappa 0.349-0.064). All raters used both facts and intuition. The rater's reliance on the facts was significantly associated with classifying those subjects who had no proving response [rater 1, P<0.001; rater 2, P<0.001]. Raters used significantly higher intuition scores when classifying a prover [rater 2, P= 0.001; rater 3, P= 0.012]. Issues regarding the education and practice of homeopathy are discussed.     

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.      

Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

Estimating the cost of expanding an apheresis program

To determine the cost of expanding blood product operations, the concept of marginal cost must be used. This article reports the development and implementation of a method of costing increases in collecting plasma using apheresis operations. The model takes into account the fact that certain resource inputs--notably, direct labor and machines--increase in discrete steps rather than in a continuous manner. To address this fact, a stepwise cost analysis function was developed, which related operating costs to the volume of apheresis collections. This function was used to predict the marginal costs of potential increases in the supply of plasma at a blood center in Canada. Differences were noted in the cost of plasma in Canada and the United States, much of which could be attributed to different standards regarding the volume of plasma per collection and to differences in pricing materials.