Chaotic sepsis and the magic bullet.

All physiological systems have complex interactions--both intrinsic and with external systems. Sepsis is an archetypal example of a self-regulating complex system, with multiple cascading non-linear interactions and feedbacks, acting in series and in parallel, to form a "scale-free" network. The process of sepsis may be modelled in terms of complexity theory as an iterative progression from a stable, homeostatic pathway or attractor to an unstable attractor of immunological dissonance and death. Given the convolutions of the septic attractor, complexity theory neatly explains why so many "magic bullet" therapies for sepsis have failed when given alone, since reductionist approaches which test individual treatments one at a time are highly unlikely to be effective in isolation. A new methodology of synchronously testing multiple therapies needs to be developed.

Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis.

BACKGROUND: Previous studies suggest that bronchoscopy and a single induced sputum sample are equally effective for diagnosing pulmonary tuberculosis. METHODS: In a prospective study of subjects with possibly active pulmonary tuberculosis, the diagnostic yield of three induced sputum tests was compared with that of bronchoscopy. Subjects either produced no sputum or (acid fast) smear negative sputum. Bronchoscopy was only performed if at least two induced sputum samples were smear negative. RESULTS: Of 129 subjects who completed all tests, 27 (21%) had smear negative and culture positive specimens, 14 (52%) on bronchoscopy and 26 (96%) on induced sputum (p<0.005). One patient was culture positive on bronchoscopy alone compared with 13 on induced sputum alone; 13 were culture positive on both tests. Induced sputum positivity was strikingly more prevalent when chest radiographic appearances showed any features of active tuberculosis (20/63, 32%) than when appearances suggested inactivity (1/44, 2%; p<0.005). Induced sputum costs were about one third those of bronchoscopy, and the ratio of costs of the two tests per case of tuberculosis diagnosed could be as much as 1:6. CONCLUSIONS: In subjects investigated for possibly active or inactive tuberculosis who produce no sputum or have smear negative sputum, the most cost effective strategy is to perform three induced sputum tests without bronchoscopy. Induced sputum testing carries a high risk of nosocomial tuberculosis unless performed in respiratory isolation conditions. The cost benefits shown could be lost if risk management measures are not observed.

Management of complicated parapneumonic effusions and thoracic empyema.

The optimal management of loculated parapneumonic effusions and empyema includes breakdown of adhesions to effect drainage of infected pleural fluid. The use of fibrinolytics intrapleurally appears to enhance intercostal tube drainage, reducing the requirement for subsequent surgical mechanical debridement. This article discusses the evidence for intrapleural fibrinolytics, their good safety profile and the practicalities of dose and administration. It also reviews early surgical intervention, which may be indicated for medical treatment failure and, some would argue, as a suitable alternative to other medical interventions.

r-hirudin as anticoagulant for cardiopulmonary bypass.

A 68-year-old woman with unstable angina and an episode of ventricular fibrillation developed a persistent and recurrent rash due to heparin. Medical therapy was continued with danaproid. For cardiopulmonary bypass and coronary artery grafting, r-hirudin was used as the anticoagulant. There were no thrombotic or coagulopathic complications. There is still no ideal alternative to unfractionated heparin for anticoagulation for cardiopulmonary bypass. The use of r-hirudin was successful and we describe our anticoagulant strategy.

Bronchiolitis obliterans organising pneumonia associated with the use of nitrofurantoin.

The spectrum of nitrofurantoin lung injury continues to widen. The case histories are presented of two patients who developed lung disease associated with the use of nitrofurantoin with histological features of bronchiolitis obliterans organising pneumonia (BOOP), a rare but recognised form of drug induced injury. The two middle aged women presented with respiratory symptoms after prolonged treatment with nitrofurantoin. Both had impaired lung function and abnormal computed tomographic scans, and their condition improved when nitrofurantoin was withdrawn and corticosteroid treatment commenced. The favourable outcome in these two patients contrasts with the fatal outcome of the two other reported cases of nitrofurantoin induced BOOP. We suggest that the previous classification of nitrofurantoin induced lung injury into "acute" and "chronic" injury is an oversimplification in view of the wide variety of pathological entities that have subsequently emerged.

Pulsed-field gel electrophoresis is a useful tool in the monitoring of methicillin-resistant Staphylococcus aureus epidemic outbreaks in the intensive care unit.

We wished to determine how pulsed-field gel electrophoresis may be of use in monitoring methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in the intensive care unit (ICU). A retrospective epidemiological analysis was conducted. All 27 ICU patients and 11 patients from other hospital wards from whom MRSA was isolated over a one year period were included in the study. Seventeen of the 27 ICU MRSA isolates were analysed by pulsed-field gel electrophoresis for clonality and compared with the 11 other hospital isolates genotypes over the same period. During three MRSA outbreaks, five MRSA genotypes were identified in ICU whilst the same five genotypes and three additional were found in the rest of the hospital. Pulsed-field gel electrophoresis analysis was useful in identifying clonality of ICU MRSA infections and establishing that they were imported from hospital wards, rather than arising de novo in ICU. We were further able to identify clonal clusters within the unit linked by temporal and geographical proximity, suggestive of cross-infection. Pulsed-field gel electrophoresis typing might be additionally useful in tracing the source of human and/or environmental factors if a genotype were persistently identified.

Multidrug resistant tuberculosis in Auckland 1988-95.

AIMS: To review all cases of multidrug resistant tuberculosis (MDRTb) in Auckland between 1988-95; and to look for ways in which the diagnosis and management may be improved. METHODS: Cases of multidrug resistant tuberculosis were identified from Green Lane Hospital tuberculosis laboratory records. Clinical details were obtained from hospital case records, and radiographs were reviewed. RESULTS: Nine of the 838 (1.1%) confirmed cases of tuberculosis had multidrug resistant tuberculosis. Eight were foreign-born and four had previously been treated for tuberculosis. Three patients underwent thoracic surgery. Two patients died and one was not treated, No relapses have occurred. Potential to improve on the treatment given was evident in retrospect in three patients. CONCLUSIONS: Assessment of risk factors for multidrug resistant tuberculosis and early transfer of specimens to a tuberculosis reference laboratory are required to enable multidrug resistance to be identified early. Extensive disease, drug side effects and coexistent medical problems make MDRTb very difficult to cure. Directly observed therapy is recommended for multidrug resistant tuberculosis cases and is underutilised in Auckland.

Early intervention for young children with developmental delay: the Portage approach.

It is now 20 years since the Portage Home Teaching model of early intervention was introduced into the UK. In this paper, an overview of the Portage Model and rationale is provided, achievements over the past two decades are noted and related research and evaluation studies are reviewed. A number of areas for future development are also highlighted. These include: issues of quality control; the multi-cultural dimension of Portage; multi-agency collaboration; professional training needs of Portage personnel; and influencing central government policy relating to families who have a young child with special needs.

Prospective, controlled, double-blind study of i.v. tenoxicam for analgesia after thoracotomy.

We have shown that a single i.v. dose of tenoxicam 20 mg, after thoracotomy, when compared with placebo in 20 patients (with one exclusion), was associated with a reduction in consumption of papaveretum, assessed by patient-controlled analgesia, of 2.2 mg h-1 (22%) to 4 h and 1.4 mg h-1 (23%) to 12 h after operation (repeated measures analysis of variance: P less than 0.01). There was no reduction from 12 to 24 h. There was no significant difference between groups in pain scores or in side effects.

A comparative study of the inhibition of hepatic aldehyde dehydrogenases in the rat by methyltetrazolethiol, calcium carbimide, and disulfiram.

Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam. Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration. The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague-Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D). The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral). The relative magnitude of maximal inhibition of low Km ALDH was CC greater than D greater than MTT. The relative duration of enzyme inhibition was D greater than MTT greater than CC. High Km ALDH was only inhibited by CC. Hepatic low Km ALDH was selectively inhibited by s.c. and oral administration of 125 mg/kg MTT. For s.c. administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose. Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c. administration of the same dose. The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h). The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC greater than MTT. The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment. Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D.