Relationship between body composition, peripheral muscle strength and functional exercise capacity in patients with severe chronic obstructive pulmonary disease.

The influence of body composition and peripheral muscle strength on 6-minute walk distance was assessed by performing dual energy X-ray absorptiometry scanning, spirometry and dynamometry testing in 13 men and 13 women with severe chronic obstructive pulmonary disease. Multivariate modelling showed that 76% of the variance in 6-minute walk distance could be explained by an equation incorporating lung function, quadriceps strength and lean leg mass. These findings indicate an important role for lower limb strength measures in pulmonary rehabilitation training programmes.

Paraspinal desmoid fibromatosis after lumbar epidural analgesia.

A 14-year-old girl with cerebral palsy presented for bilateral lower limb surgery for spasticity. A lumbar epidural catheter was sited under general anaesthesia on the third attempt and used intra-operatively with good effect. A local anaesthetic infusion was used for postoperative analgesia but was noted to be leaking under the dressing with a patchy, unilateral block. The catheter was therefore removed on the second postoperative day. Following discharge, the patient progressively developed new back and leg pain for which she was re-admitted seven weeks later. This was investigated and initially thought to be myositis of the erector spinae muscles on magnetic resonance imaging. When the patient failed to respond to treatment, a muscle biopsy demonstrated desmoid fibromatosis. Trauma may cause or accelerate the development of desmoid fibromatosis, which has also been theorised to arise from scar tissue in previously injured areas. We hypothesise that challenging epidural placement or the leakage of the local anaesthetic agent into the surrounding muscular tissue, inducing local myonecrosis, could have been the triggering or accelerating event in tumour development. This may be the first reported case of extra-abdominal desmoid fibromatosis in association with epidural placement.

Antigenic diversity of the circumsporozoite proteins in the Plasmodium cynomolgi complex.

Antigenic diversity was observed in the circumsporozoite (CS) proteins of five of the six Plasmodium cynomolgi isolates (NIH, Mulligan, London, Gombak, Ceylon, RO) that we examined. Monoclonal antibodies were produced against salivary gland sporozoites of three of the isolates. Interaction of these monoclonal antibodies with the sporozoites was isolate specific, the exception being the anti-NIH monoclonals which also reacted with Mulligan strain sporozoites. Inhibition of binding between the different monoclonal antibodies indicated that for each of the NIH, London, and Gombak strains, the homologous monoclonals were recognizing the same or a topographically close immunodominant epitope on the respective CS protein. Also the binding of a polyvalent anti-NIH rhesus serum to the homologous antigen could only be inhibited by anti-NIH monoclonal antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis of sporozoite extracts demonstrated clear differences in the apparent molecular weights of the CS proteins of four of the six isolates. This is the first study which provides evidence of antigenic diversity in the CS proteins of different isolates of a primate plasmodial species.

Clinical pharmacokinetics of propafenone.

Propafenone is a class 1C antiarrhythmic agent which is administered as a racemate of S(+)- and R(-)-enantiomers. It is well absorbed and is predominantly bound to alpha 1-acid glycoprotein in the plasma. The enantiomers display stereoselective disposition characteristics, the R-enantiomer being cleared more quickly. The hepatic metabolism of propafenone is polymorphic and genetically determined: about 10% of Caucasians have a reduced capacity to hydroxylate the drug. This polymorphic metabolism accounts for the marked interindividual variability in the relationships between dose and concentration, and between concentration and pharmacodynamic effects. During long term administration, the metabolism is saturable in patients with the 'extensive metaboliser' phenotype, leading to accumulation of the parent compound. Propafenone blocks fast inward sodium channels in a frequency-dependent manner, and also has moderate beta-blocking effects. Both the enantiomers and the 5-OH metabolite have a potency to block sodium channels comparable with that of the parent compound. The S-enantiomer is a more potent beta-antagonist than the R-enantiomer. Propafenone typically slows conduction markedly but only modestly prolongs refractoriness. These cardiac effects are determined by the extent of its myocardial accumulation. The drug should be used with caution in patients with serious structural heart disease, as it may cause or aggravate life-threatening arrhythmias. Significant interactions occur when propafenone is coadministered with other drugs. It increases the plasma concentrations of digoxin, warfarin, metoprolol and propranolol as well as enhancing their respective pharmacodynamic effects. Doses of these drugs should therefore be decreased if they are coadministered with propafenone.

Comparison of atrial overdrive pacing with and without extrastimuli for termination of atrial flutter.

Atrial overdrive pacing has been successfully used to terminate atrial flutter. This study compared the efficacy of atrial extrastimuli following a rapid pacing train to overdrive pacing without atrial extrastimuli for the termination of atrial flutter. Patients were randomized to treatments of short or long burst atrial overdrive pacing or atrial overdrive pacing followed by atrial extrastimuli in a crossover study design. A total of 22 patients (73%) had successful conversion of atrial flutter to sinus rhythm. The success rates in patients exposed to each therapy, including crossover therapies, were 62% with the atrial extrastimuli method, 8% with the short burst pacing method, and 8% with the long burst pacing method (p less than 0.001). Transient atrial fibrillation developed in 15 patients and in 9 of these this arrhythmia preceded conversion to sinus rhythm. Sustained atrial fibrillation was induced in 3 additional patients but never with the atrial extrastimuli method. In conclusion, the method of delivering atrial extrastimuli after a rapid pacing train is highly efficacious for the termination of atrial flutter. Furthermore, this method is more effective than atrial overdrive pacing methods delivered at the same pacing cycle length. These observations have important implications for the programming of antitachycardia pacemakers.

Catheter ablation using radiofrequency or low-energy direct current in pediatric patients with the Wolff-Parkinson-White syndrome.

Percutaneous ablation of accessory pathways was performed in 22 consecutive children and adolescents (9 boys and 13 girls, age range 8 to 18 years). Low-energy direct current (DC) was used exclusively in the first 6 patients, whereas ablation was performed with radiofrequency energy in the following 16. Accessory pathways were located in the left free wall in 15 patients, were posteroseptal in 3, were in the right free wall in 3 and were anteroseptal in 1. A concealed accessory pathway was present in 7 patients (32%). There was no significant difference in clinical or electrophysiologic variables between both groups. Catheter ablation was successful in the initial 6 patients using low-energy DC, as compared with 13 of 16 patients using radiofrequency ablation. Low-energy DC was successful as a backup power source in all 3 patients who had unsuccessful radiofrequency ablation. There was no complication. The median procedural and fluoroscopic times for successful ablation were 2.5 hours and 49 minutes, respectively (p = NS between both power sources). Accessory pathway conduction recurred in 2 patients (33%) who had low-energy DC as compared with 1 (6%) who had radiofrequency ablation (p = NS). These 3 patients had successful reablation of their accessory pathways. In children and adolescents with accessory pathways, both new power sources compare favorably, with an overall success rate of ablation of 100% (22 of 22 patients). Radiofrequency ablation should be used initially because it does not require general anesthesia and is associated with a lower rate of recurrence of accessory pathway conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Risks of developing supraventricular and ventricular tachyarrhythmias after implantation of a cardioverter-defibrillator, and timing the activation of arrhythmia termination therapies.

The clinical courses of 39 consecutive recipients (mean age 61 +/- 12 years, and mean left ventricular ejection fraction 0.32 +/- 0.15) of an automatic implantable cardioverter-defibrillator (ICD) were examined to determine the risks of developing ventricular tachycardia (VT) and supraventricular tachyarrhythmias (SVT) after surgery, with ventricular response rates fulfilling ICD detection criteria. ICD system leads were implanted by thoracotomy in 25 patients and by using nonthoracotomy lead systems in 14. Six patients (18%) developed SVT after surgery, whereas 14 (36%) developed sustained VT. The median times to the development of both SVT and VT were 2 days. By actuarial analysis, the probability of developing VT after surgery was significantly greater than that of SVT during hospitalization (p = 0.04). This significant excess of postoperative VT over SVT was most marked in patients aged < or = 61 years, those who received nonthoracotomy rather than epicardial lead systems, those who presented with VT rather than ventricular fibrillation, and those who received > 20 intraoperative defibrillation shocks. These observations recommend the activation of ICD therapies immediately after implantation.

Antiarrhythmic drug effects on QT interval dispersion in patients undergoing electropharmacologic testing for ventricular tachycardia and fibrillation.

The effects of antiarrhythmic drugs on QT interval dispersion as a predictor of antiarrhythmic drug therapy has not been rigorously assessed. This study was performed to determine whether the effects of antiarrhythmic drugs on QT interval dispersion predict antiarrhythmic drug response in patients undergoing electropharmacologic testing for ventricular tachycardiarrythmias. Precordial QT intervals and QT interval dispersions were measured at baseline and during steady-state antiarrhythmic drug therapy in 72 consecutive patients with documented coronary artery disease and remote myocardial infarction presenting with spontaneous sustained ventricular tachyarrhythmias who underwent electropharmacologic studies to assess arrhythmia suppression. QT interval dispersion was similar at baseline in drug responders (42 +/- 21 ms) and drug nonresponders (46 +/- 21 ms), whereas during antiarrhythmic therapy QT interval dispersion was shorter in drug responders (33 +/- 15 ms) than in drug nonresponders (55 +/- 29 ms, p <0.001). QT interval dispersion was shorter in 7 drug responders during their effective drug trials (27 +/- 14 ms) than during their ineffective drug trials (47 +/- 24 ms, n = 9, p <0.05). QT dispersion < or = 50 ms (p <0.002) and a patent infarct-related artery (p <0.003) were independent predictors of antiarrhythmic therapy. The positive and negative predictive value of QT interval dispersion during drug therapy to predict a successful drug response was 32% and 96%, respectively. QT interval dispersion predicted the outcome of electropharmacologic studies independent of infarct-related artery patency. QT interval dispersion >50 ms during drug therapy was associated with ineffective drug therapy.

Assessment of the humoral and cell-mediated immunity against the Plasmodium falciparum vaccine candidates circumsporozoite protein and SPf66 in adults living in highly endemic malarious areas of Papua New Guinea.

To assess natural immunity against the circumsporozoite (CS) protein and the synthetic vaccine SPf66, immunologic studies were carried out in a highly endemic malarious area of Papua New Guinea. Antibody prevalence, antibody titers, and T cell proliferation against both antigens were measured in 214 adults. Immunologic data were analyzed with respect to longitudinal malariologic and morbidity data. Evidence of genetic traits such as glucose-6-phosphate dehydrogenase deficiency and ovalocytosis was analyzed. Antibody prevalence was high, with 79% and 84% for CS protein and SPf66, respectively, while T cell proliferation was infrequent and low, with 14% and 12% responders, respectively. Anti-CS protein antibodies increased with age but showed no association to malaria indices or morbidity. No protective value was observed with T cell responses or with humoral response to SPf66. These results provide a first description of naturally developed immunity against SPf66 and suggest further studies in to fully understand the mechanism of immunity against this antigen.

Relationship between humoral response to Plasmodium falciparum merozoite surface antigen-2 and malaria morbidity in a highly endemic area of Papua New Guinea.

The prevalence and concentration of antibodies to merozoite surface antigen-2 (MSA-2) were measured in blood samples collected during a cross-sectional survey. Antibodies were measured by enzyme-linked immunosorbent assay using two recombinant proteins that closely approximated the full-length mature MSA-2 polypeptides expressed by the Plasmodium falciparum isolate FC27 and the cloned line 3D7 and that were representative of the dimorphic forms of MSA-2. Antibodies were also measured to a form of the 3D7 MSA-2 lacking the central repetitive sequences (d3D7). High antibody prevalence was observed to all three antigens: the overall prevalence of IgG to FC27, 3D7, and d3D7 was 91%, 90%, and 90%, respectively. The majority of individuals > or = 5 years of age had antibodies to both forms of MSA-2. The geometric mean antibody units increased with age with a plateau being reached by 15-20 years of age. There was a significant positive association of antibody prevalence with both the presence of the parasite and an enlarged spleen in children. This study provides the first evidence that antibodies against nonrepeat regions of MSA-2 are associated with fewer fever episodes and less anemia, both known to be indicators of malaria morbidity.

Humoral response to Plasmodium falciparum ring-infected erythrocyte surface antigen in a highly endemic area of Papua New Guinea.

The prevalence and concentration of antibodies to ring-infected erythrocyte surface antigen (RESA) were measured in blood samples collected during a cross-sectional survey conducted in Papua New Guinea. Antibodies were measured by enzyme-linked immunosorbent assay to the recombinant RESA protein in 1,398 subjects and to RESA 8 and RESA 11 synthetic peptides in a subsample of 200 adults. Overall, the seropositivity rate to recombinant RESA was 66% and the geometric mean antibody concentration was 28 micrograms/ml. There was a slow increase in antibody prevalence and concentration with age that continued to occur even after 40 years of age. In children less than 10 years of age, there was a significant positive correlation between both RESA antibody prevalence and concentration and concurrent infection with Plasmodium falciparum. The opposite was true in adults more than 20 years of age, with those having a high antibody concentration to RESA being less likely to be parasitemic at the time of the survey. This observation was consistent with the finding of a weak but significant negative correlation between log antibody concentration and log P. falciparum density, which was mainly found in adults. No consistent correlation was found between humoral immune response to RESA and morbidity indicators.

Nocardia infection in the acquired immunodeficiency syndrome.

A case of Nocardia asteroides pneumonia in a patient with the acquired immunodeficiency syndrome who was intolerant of sulfadiazine is described. On cefuroxime, the patient had a complete resolution of his Nocardia pneumonia. Disk-diffusion and broth microdilution antibiotic susceptibility testing (MIC less than or equal to 2 micrograms/ml) strongly supported the use of cefuroxime as treatment in this patient. Susceptibility testing with newer cephalosporins should be considered for all significant Nocardia isolates.

Changes in abundance and behaviour of vector mosquitoes induced by land use during the development of an oil palm plantation in Sarawak.

Surveys were conducted of adult and immature mosquitoes in an area undergoing oil palm development in north Sarawak. Point prevalence data from 2 sites were collected annually, coinciding with annual phases of forest clearing, burning/cultivation, and maintenance. Major habitat perturbation during the forest/clearing transition shifted the major mosquito faunal equilibrium in terms of species composition, relative density and occurrence. Analyses of variance showed that the mean numbers of 4 species of Anopheles decreased significantly after forest clearing. Relative densities of immature stages decreased after forest clearing, but A. letifer and Culex tritaeniorhynchus remained relatively unchanged after the second year. Comparisons with the pre-development forest stage showed that the reductions in person-biting rates, adult survival and combined entomological inoculation rates (EIR) of A. donaldi and A. letifer decreased the risk of malaria transmission by 90% over the 4 years period. Concomitant reductions in EIR and annual malaria incidence were also correlated. This study highlighted the 'law of unintended consequences', since 2 contrasting effects were observed: reduction of malaria vectors but concomitant increase of dengue vectors.

Area effects of bednet use in a malaria-endemic area in Papua New Guinea.

Relationships between area coverage with insecticide-free bednets and prevalence of Plasmodium falciparum were investigated in 7 community-based surveys over a 33-month period in 1990-93 in 6 villages in the Wosera area of Papua New Guinea. Spatial patterns in circumsporozoite rates for P. falciparum, P. vivax isomorphs K210 and K247, and P. malariae, and the proportions of mosquito blood meals positive for specific human, goat, cat, dog and pig antigens were determined using ELISAs. P. falciparum prevalence in humans was better explained by bednet coverage in the immediate vicinity than by personal protection alone. Circumsporozoite rates for both P. falciparum and P. vivax were also inversely related to coverage with bednets. There was some increase in zoophagy in areas with high coverage, but relatively little effect on the human blood index or on overall mosquito densities. In this setting, protracted use of untreated bednets apparently reduces sporozoite rates, and the associated effects on prevalence are greater than can be accounted for by personal protection. Even at high bednet coverage most anophelines feed on human hosts, so the decreased sporozoite rates are likely to be largely due to reduction of mosquito survival. This finding highlights the importance of local vector ecology for outcomes of bednet programmes and suggests that area effects of untreated bednets should be reassessed in other settings.

Anopheles flavirostris incriminated as a vector of malaria and Bancroftian filariasis in Banggi Island, Sabah, Malaysia.

Seven villages in Banggi Island, Sabah, Malaysia, were surveyed four times to evaluate the roles of local mosquitoes as vectors of malaria and Bancroftian filariasis. 11 species of Anopheles were found biting man. 53.9% of the anophelines caught were An. flavirostris, 27.1% An. balabacensis, 6% An. donaldi and 4.2% An. subpictus. Infective malaria sporozoites, probably of human origin, were found in two of 336 An. flavirostris and 12 of 308 An. balabacensis. Sporozoites, probably of a non-human Plasmodium, were found in An. umbrosus. Nine of 1001 An. flavirostris and four of 365 An. balabacensis harboured L2 or L3 filarial larvae identified as those of Wuchereria bancrofti. This is the first record of An. flavirostris as a natural vector of malaria and W. bancrofti in Sabah.

Malaria: how useful are clinical criteria for improving the diagnosis in a highly endemic area?

To assess the validity of clinical criteria, we investigated 2096 outpatients diagnosed as malaria cases by nurses at a rural health subcentre in a highly endemic area of Papua New Guinea. 73% of the children < 10 years old had a positive blood slide for any species of Plasmodium and 32% had > or = 10,000 P. falciparum parasites per microL. For adults the frequencies were 51% and 9%, respectively. Stepwise logistic regression identified spleen size, no cough, temperature, no chest indrawing, and normal stools as significant predictors for a positive blood slide in children; no cough and normal stools predicted a positive blood slide in adults. Fever, no cough, vomiting, and enlarged spleen were significant predictors for a P. falciparum parasitaemia > or = 10,000/microL in children; in adults the only predictor was vomiting. In children the association of no cough and enlarged spleen had the best predictive value for a positive blood slide, and a temperature > or = 38 degrees C had the best predictive value for a P. falciparum parasitaemia > or = 10,000 microL. In adults, no major symptom had a good predictive value for a positive blood slide but vomiting had the best predictive value for a P. falciparum parasitaemia > or = 10,000/microL. When microscopy is not available, these findings can help in areas of high endemicity to determine which patients with a history of fever are most likely to have malaria and, more importantly, for which patients another diagnosis should be strongly considered.

Associations of peak shifts in age--prevalence for human malarias with bednet coverage.

Effects of bednet coverage (C) on prevalence of malaria were analysed using data from 1990-92 from 9 Papua New Guinean villages. Effects of coverage varied by age, resulting in a shift in age of peak prevalence from 4.7 (C = 0%) to 11.6 (C = 100%) years for Plasmodium falciparum, from 3.4 to 4.9 years for P. vivax and from 11.0 to 16.8 years for P. malariae. In small areas with no bednets the age distribution of P. falciparum parasitaemia was like that of a holoendemic area. Where coverage was complete the pattern corresponded to mesoendemicity. Thus, protracted use of bednets can result in profound changes in the endemicity of malaria even when coverage is incomplete and without insecticide treatment. Average entomological inoculation rates (EIRs) estimated from indoor landing rates on individuals without bednets were 35, 12 and 10 infectious bites per person per annum for P. falciparum, P. vivax and P. malariae, respectively. Logistic regression analyses indicated that the EIR estimate for P. falciparum was related to prevalence of this species independently of effects of bednet coverage. However, the recent EIR still accounted for much less variation than did the bednets. A similar pattern was seen for P. malariae, while there were no significant relationships between the recent EIR and the parasite positivity for P. vivax. It is concluded that short-term variations in inoculation rate are not important determinants of parasite prevalence in this population.

Acute heart failure: determinants of outcome.

We prospectively studied 69 consecutive patients hospitalized with a primary diagnosis of acute left ventricular failure so as to assess the impact of vasodilators on incidence and morbidity of acute symptomatic left ventricular failure. The determinants of duration of hospitalization, in-hospital mortality and symptomatic status 2 months after discharge were examined. There were 9 in-hospital deaths (13%), and survival at 60 days was 77%. Median duration of hospitalization was 9 days, and 33% of the surviving patients remained in New York Heart Association functional class III-IV 60 days subsequent to discharge. Of the patients, 49 (76%) had previously received treatment for left ventricular failure: 30 (61%) of these had received vasodilators, most commonly angiotensin converting enzyme inhibitors and nitrates. Ischaemic chest pain was present in 34 (49%) of the patients. Acute utilization of vasodilators (45% of patients) was largely limited to nitrate therapy associated with ischaemic chest pain (P less than 0.01). Multiple logistic regression revealed previous left ventricular failure, advanced age and hypokalaemia as significant correlates of prolonged hospitalization (greater than 9 days). Previous left ventricular failure was also predictive of persistent severe disability two months subsequent to discharge. No factor was a significant predictor of in-hospital death. Although preceding treatment with digoxin and incremental angiotensin converting enzyme inhibitor therapy tended to predict brief hospitalization, the parameter of acute ischaemia, other biochemical anomalies and modes of acute or chronic therapy were not significant correlates of any end point. We conclude that preceding disability, rather than mode of treatment, predicts an adverse outcome in acute left ventricular failure.

Effect of diet on biting, oviposition, and survival of Aedes aegypti (Diptera: Culicidae).

The effect of adult diet on host biting, sugar probing and water probing patterns, oviposition behavior, and survival of Aedes aegypti (L.) from Charters Towers, Australia, were tested in the laboratory. The 7 diets were as follows: (1) starvation, (2) water, (3) 10% sugar, (4) blood, (5) blood with water supplement, (6) blood with 10% sugar supplement, and (7) blood with 3% sugar supplement. Biting, probing, oviposition, and survival observations were made every 6 h (0600-0800 hours, 1200-1400 hours, 1800-2000 hours, 2400-0200 hours). Biting frequency on the blood with 3% sugar diet (0.26 feeds per mosquito per 6 h) and the blood with 10% sugar diet (0.23 feeds per mosquito per 6 h) was significantly less than on blood (0.51 feeds per mosquito per 6 h) and 10% sugar (0.40 feeds per mosquito per 6 h) alone. Biting frequency was not significantly different between blood with water (0.47 feeds per mosquito per 6 h) and blood alone (0.51 feeds per mosquito per 6 h). Biting and oviposition occurred throughout the day, peaking between 1800 and 2000 hours and between 2000 and 2400 hours, respectively. Biting frequency with a 3% sugar supplement decreased after the 1st oviposition cycle on day 6 compared with unsupplemented biting. The presence of sugar delayed or inhibited oviposition. Females with access to blood with water bit and oviposited concurrently on days 4-6, 8-9, and 11, indicating a 3-d gonotrophic cycle. Survival on blood alone was not significantly lower than survival on sugar and water supplemented diets. Behavior of the Charters Towers strain proved to be significantly influenced by diet, and biting occurred opportunistically without regard for previously observed crepuscular or diurnal rhythms. The biting frequencies observed were the highest yet recorded for this species, which indicates that the vectorial capacity of the Australian Ae. aegypti may be underestimated severely.

Spatial and temporal variation in abundance of Anopheles (Diptera:Culicidae) in a malaria endemic area in Papua New Guinea.

Abundance of anophelines in 10 villages in the Wosera area of Papua New Guinea was monitored during 1990-1993. Of 85,197 anophelines collected in 1,276 paired indoor and outdoor landing catches, 40.4% were Anopheles koliensis Owen, 36.7% An. punctulatus Donitz, 14.3% An. karwari (James), 4.9% An. farauti s.l. Laveran, 3.1%, An, longirostris Brug, and 0.7% An. bancroftii Giles. Maps of average indoor biting rates were produced using a Bayesian conditional autoregressive model which allowed for heterogeneities in sampling effort over time and space. Differences in spatial distributions among species were observed among and within villages and were related to the distribution of larval habitats and vegetation. Abundance of An. punctulatus and An. koliensis decreased with distance from the main waterway and probably from a sago swamp forest at 6 villages in North Wosera. Abundance of An. punctulatus was associated negatively with those of An. farauti s.l., An. longirostris, and An. bancroftii. The latter 3 species also had relatively low ratios of indoor-to-outdoor biting rates, and earlier biting times than An. punctulatus. Human blood indices of at least 0.79 were observed for all species except An. bancroftii. Abundance of all 6 species was correlated temporally with recent rainfall, but An. koliensis, An. karwari, and An. longirostris showed greater temporal variability than the other species. An punctulatus and An. koliensis tended to occur together in time and space (index of association, I = 0.85). Weaker associations were seen between An. farauti s.l. and An. longirostris (I = 0.44) and An. koliensis and An. karwari (I = 0.34). The most frequently collected species occurred together and were concentrated near the Amugu river; the remaining species tended to occur together but in different parts of the Wosera area. The importance of understanding ecological requirements of the different Anopheles vectors and their association with key household and landscape features are discussed in relation to malaria transmission and control.