Host-parasite interaction in serious infections due to gram-negative bacteria

Gram-negative rods such as Enterobacteriaceae and Pseudomonadaceae are normal habitants of the digestive tract. However, if defense mechanisms of the host are compromised by underlying diseases such as malignant neoplasms, renal insufficiency, extensive traumata, or immunosuppressive therapy, invasion of the blood-stream can occur. Gram-negative septicaemia is associated with high morbidity and mortality, despite intensive care and administration of potent antibiotics. A central role in the pathophysiology of life-threatening bacteraemia is attributed to endotoxin, a constituent of the gram-negative cell wall. This paper reviews current concepts of septic shock, the acquisition of gram-negative bacteraemia and the role of endotoxin. It also deals with a new approach to prevention and control of severe gram-negative infections using serotherapy based on the structure of endotoxin.     

Risk of otitis externa after swimming in recreational fresh water lakes containing Pseudomonas aeruginosa.

OBJECTIVE--To determine whether an outbreak of otitis externa was due to bathing in recreational fresh water lakes and to establish whether the outbreak was caused by Pseudomonas aeruginosa in the water. DESIGN--Matched case-control study. SETTING--The Achterhoek area, the Netherlands. SUBJECTS--98 cases with otitis externa and 149 controls matched for age, sex, and place of residence. MAIN OUTCOME MEASURES--Odds ratios for type of swimming water and frequency of swimming; presence of P aeruginosa in ear swabs and fresh water lakes. RESULTS--Otitis externa was strongly associated with swimming in recreational fresh water lakes in the previous two weeks (odds ratio 15.5 (95% confidence interval) 4.9 to 49.2) compared with non-swimming). The risk increased with the number of days of swimming, and subjects with recurrent ear disease had a greatly increased risk. The lakes met the Dutch bathing water standards and those set by the European Commission for faecal pollution in the summer of 1994, but P aeruginosa was isolated from all of them, as well as from the ear swabs of 78 (83%) of the cases and 3 (4%) of the controls. CONCLUSIONS--Even when current bathing water standards are met, swimming can be associated with a substantial risk of otitis externa because of exposure to P aeruginosa. People with recurrent ear disease should take special care when swimming in waters containing P aeruginosa.     

The complex nature of humanD-locus determinants: Heterogeneity within Dw3

The HLA-A and B homozygous cell, ABR, was found to be mutually nonstimulatory with Dw3-homozygous test cell 16001 (EB), and so was considered to be Dw3-homozygous. However, family studies revealed a difference in theD-locus determinant(s) inherited from the father and mother. The cells carrying the determinants derived from the paternal1,8 haplotype (a _f ) consistently stimulated the lymphocytes bearing the determinants from the maternal1,8 haplotype (ainm), but thea _m haplotype products could not stimulate those of haplotypea _f . Sincea _m is included ina _f , cell ABR behaves in population studies as a Dw3-homozygous cell. Typing forD-locus determinants showed the father to be Dw3-positive, the mother Dw3-negative. The Dw3 determinant seems not homogeneous and this should be taken into account in explaining the results withD-locus homozygous typing cells.     

Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides

Background

The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.

Results

EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.

Conclusion

DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress.     

The use of Bartonella henselae-specific age dependent IgG and IgM in diagnostic models to discriminate diseased from non-diseased in Cat Scratch Disease serology

Cat Scratch Disease (CSD) is caused by Bartonella henselae infection and is a common cause of regional lymphadenopathy. The diagnosis of CSD largely depends on serology, but is hampered by both low sensitivity and specificity of the applied IgG and IgM assays. Using an in-house ELISA, we detected a significant age-dependent increase in the IgG levels in the general population compared to CSD patients. With this knowledge, we developed diagnostic models to differentiate diseased from non-diseased persons. Evaluation of these models using samples from PCR-positive patients (n=155) and age-matched controls (n=244) showed an important increase in the assay performance if the combination of the IgG and IgM results were taken into account. If the specificity was set at 98% the sensitivity was only 45% and 32% for the IgM and IgG ELISA, respectively but increased to 59% when these results were combined. Also the use of age-dependent factors further improved the clinical relevance of the outcome raising the sensitivity to 64%. Although the sensitivity of the ELISA remains low we conclude that the use of models using the combination of both IgM and IgG test results and age-depending factors can be a useful diagnostic tool in the serodiagnosis of CSD.     

Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes

Background  

Parkinson's disease (PD) is the second most common neurodegenerative disorder. One of the most widely used techniques to diagnose PD is a Single Photon Emission Computer Tomography (SPECT) scan to visualise the integrity of the dopaminergic pathways in the brain. Despite this there remains some discussion on the value of SPECT in the differential diagnosis of PD. We did a meta-analysis of all the existing literature on the diagnostic accuracy of both pre- and post-synaptic SPECT imaging in the differential diagnosis of PD.     

The nerve supply to the clavicular part of the pectoralis major muscle: an anatomical study and clinical application of the function-preserving pectoralis major island flap

The purpose of this study was to investigate the nerve supply to the clavicular part of the pectoralis major muscle so that the innervation to this part can be maintained in the muscle-preserving pectoralis major island-flap transfer. Although methods have been described that include a limited portion of the muscle while leaving the upper parts undisturbed with an intact motor innervation, reports on anatomical studies of this nerve supply are brief. The distal distribution of the nerves, the spatial relationship to the main vascular pedicle, and the ways to preserve them during surgical procedures remain unclear. Surgically relevant features of the clavicular part of the pectoralis major muscle were studied by dissection. The nerve supply to this part was examined on 11 sides of eight formalin-fixed cadavers. Two fresh cadavers were used for dissection, intraarterial polymer injection, and application of a nerve-preserving surgical technique. In all subjects, a separate nerve innervated the clavicular and upper medial sternocostal portions of the pectoralis major muscle. This nerve arises craniomedial to the main vascular pedicle of the flap and divides into several branches. These branches run in a fascia on the deep surface of the pectoralis major muscle, superficial to the origin and distal course of the vascular pedicle. Most branches to the clavicular part end medial to the coracoid process. The course of the branches to the upper sternocostal part is more medial. Based on their anatomical findings, the authors propose a surgical technique for transfer of the pectoralis major island flap to the head and neck area through a tunnel in the deltopectoral groove, lateral to the origin of the vascular pedicle. Head and neck reconstruction was performed using this technique. The presented method is a muscle-preserving procedure that maintains maximal donor-site function and morphology.     

Linkage analysis of a derived glucose phenotype in the Genetic Analysis Workshop 13 simulated data using a variety of Haseman-Elston based regression methods

A variety of Haseman-Elston type regression procedures were used to perform a genome scan across five chromosomes, using replicates 1-5 of the Genetic Analysis Workshop 13 simulated data. The traits of interest were variables corresponding to 'baseline' and 'slope' effects derived from the fasting glucose phenotypes. Performance in terms of detecting the locations of known trait loci was poor for all methods, even when all five replicates were combined to produce a large data set (9230 sib pairs). All methods performed well, however, when applied to new simulated data in which the true genetic effects were allowed to explain a greater proportion of the overall variance.