Infrapatellar fat pad abnormalities are associated with a higher inflammatory synovial fluid cytokine profile in young adults following ACL tear.

OBJECTIVE: To evaluate the degree of knee fat pad abnormalities after acute anterior cruciate ligament (ACL) tear via magnetic resonance fat pad scoring and to assess cross-sectionally its association with synovial fluid biomarkers and with early cartilage damage as quantified via T1ρ and T2 relaxation time measurements. DESIGN: 26 patients with acute ACL tears underwent 3T MR scanning of the injured knee prior to ACL reconstruction. The presence and degree of abnormalities of the infrapatellar (IPFP) and the suprapatellar (SPFP) fat pads were scored on MR images along with grading of effusion-synovitis and synovial proliferations. Knee cartilage composition was assessed by 3T MR T1ρ and T2 mapping in six knee compartments. We quantified concentrations of 20 biomarkers in synovial fluid aspirated at the time of ACL reconstruction. Spearman rank partial correlations with adjustments for age and gender were employed to evaluate correlations of MR, particularly cartilage composition and fat pad abnormalities, and biomarker data. RESULTS: The degree of IPFP abnormality correlated positively with the synovial levels of the inflammatory cytokine markers IFN-γ (ρpartial = 0.64, 95% CI (0.26-0.85)), IL-10 (ρpartial = 0.47, 95% CI (0.04-0.75)), IL-6 (ρpartial = 0.56, 95% CI (0.16-0.81)), IL-8 (ρpartial = 0.49, 95% CI (0.06-0.76)), TNF-α (ρpartial = 0.55, 95% CI (0.14-0.80)) and of the chondrodestructive markers MMP-1 and -3 (MMP-1: ρpartial = 0.57, 95% CI (0.17-0.81); MMP-3: ρpartial = 0.60, 95% CI (0.21-0.83)). IPFP abnormalities were significantly associated with higher T1ρ and T2 values in the trochlear cartilage (T1ρ: ρpartial = 0.55, 95% CI (0.15-0.80); T2: ρpartial = 0.58, 95% CI (0.18-0.81)) and with higher T2 values in the medial femoral, medial tibial as well as in patellar cartilage (0.45 ≤ ρpartial ≤ 0.59). Correlations between SPFP abnormalities and synovial markers were not significant except for IL-6 (ρpartial = 0.57, 95% CI (0.17-0.81)). CONCLUSIONS: This exploratory study suggests that acute ACL rupture can be associated with damage to knee tissues such as the inferior fat pad of the knee. Such fat pad injury could be partially responsible for the apparent post-injury pro-inflammatory response noted in ACL-injured individuals. However, future longitudinal studies are needed to link ACL-rupture associated fat pad injury with important patient outcomes such as the development of posttraumatic osteoarthritis.

Sepsis: the critical role of iron.

Sepsis is a global problem which is exacerbated by increasing bacterial resistance to antibiotics. However, mechanisms of natural resistance can be extremely effective, and need to be exploited, but the availability of iron is critical for controlling bacterial growth. The diagnosis of sepsis and possible strategies for limiting iron availability are discussed.

Iron and infection: new developments and their implications.

Unsaturated transferrin in plasma ensures that the amount of free ferric iron available to bacteria is about 10(-18) mol/L. This low iron environment is essential for the bacteriostatic and bactericidal systems in blood, lymph, and exudates. Antibacterial systems are abolished when iron becomes freely available. This results in rapid extracellular bacterial growth and greatly increased bacterial virulence. In human plasma, a fall in Eh (oxidation-reduction potential) or pH results in the abolition or marked reduction of its bactericidal properties. This is highly relevant to infection after trauma, where a fall in Eh and pH frequently accompanies tissue damage. Bacterial resistance to antibiotics has put the treatment of serious infections in jeopardy. Reinforcement of natural means of resistance needs to be explored, as well as examining new antibacterials that interfere with bacterial iron metabolism.

Topographic quantitative EEG measures of alpha and theta power changes during caffeine withdrawal: preliminary findings from normal subjects.

Neurophysiological consequences of withdrawal from caffeine are poorly understood. In particular, quantitative studies of EEG changes that may occur during the period of caffeine abstinence in caffeine dependent individuals have not been reported. In this pilot study, 13 physically- and psychiatrically-normal caffeine users were asked to abstain from caffeine for a period of 4 days. Quantitative EEGs were obtained prior to stopping caffeine and on Days 1, 2, and 4 of the caffeine abstinence period. Results indicated that significant increases in alpha and theta absolute power accompany the caffeine withdrawal process with return to the pre-abstinent EEG levels when caffeine usage is resumed. The implications of these findings are discussed with special reference to the possible need to control for the variable of caffeine usage in quantitative EEG studies of other phenomena.

A standardized form for DSM-IV review of symptoms and mental status examination for students and residents.

A common error by medical students and residents is the inadvertent omission of some part of the mental status examination or failure to screen for a psychiatric diagnosis that is not evident on the patient's presentation. The authors introduce a structured questionnaire and standardized form to guide psychiatric and generalist medical trainees through the mental status examination. Based on criteria from the Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV), the questionnaire and form are intended to facilitate a psychiatric review of patients without missing key points.

The role of Eh, pH and iron in the bactericidal power of human plasma.

The bactericidal power of fresh human plasma against Klebsiella pneumoniae and Escherichia coli was extremely sensitive to changes in Eh and pH. At a high Eh (approx. +200 mV) the bacteria were destroyed, but rapid regrowth occurred when the Eh was lowered to approx. -400 mV. Abolition of the bactericidal effect was also produced by adding ferric iron at a high Eh (approx. +200 mV). Lowering the pH to 6.50 reduced or prevented the bactericidal effect. These results are probably related to the availability of iron for bacterial growth, and could be important for understanding the development of infection in injured or diseased tissue.

Hemochromatosis, iron and septicemia caused by Vibrio vulnificus.

Vibrio vulnificus is killed by normal human blood but grows rapidly in blood from patients with hemochromatosis. It also grows in normal blood if the saturation of the transferrin is increased or if hematin, which contains iron, is added. It is suggested that the increased availability of iron in the blood of patients with chronic iron overload is responsible for their enhanced susceptibility to infection with V vulnificus.

The critical role of iron in some clinical infections.

The role of iron in certain clinical infections is revealed. In normal persons the antibacterial and antifungal properties of blood and other tissue fluids cannot be maintained unless there are exceptionally low levels of available iron. This is controlled by the presence of the unsaturated iron-binding proteins, transferrin and lactoferrin. In several clinical conditions an abnormal availability of iron is responsible for fatal septicaemia. This is because the phagocytic system is overwhelmed by rapidly growing organisms when iron is freely available.

The bactericidal power of the blood and plasma of patients with burns.

Patients with burns are unusually susceptible to bacterial infections, but so far there is no satisfactory explanation for this lack of resistance. Since resistance to infection involves many different mechanisms, examination of individual components of the immune system may not sufficiently explain the underlying reasons for increased susceptibility. The use of whole blood for antibacterial tests has the advantage that all the immune systems present in that fluid compartment can take part in the bactericidal effect. Tests with Klebsiella pneumoniae and Staphylococcus aureus showed no evidence that the bactericidal power of the blood and plasma of patients with burns was less than that of normal control plasma. This suggests that the solution to the problem of increased susceptibility to infection in patients with burns does not lie with the blood but must be looked for elsewhere.

Bacterial virulence and host selection: bacteria "select" patients to infect.

A clinically lethal strain of Pseudomonas aeruginosa was tested and its growth patterns in normal plasma and in normal whole blood clotted with thrombin were compared. Two stock cultures were used; one was maintained in liquid nitrogen and one was passed from plate to plate 24 times on blood agar plates at room temperature. The results showed that plasma alone and whole blood controlled the growth of a clinically pathogenic strain of P. aeruginosa consistently and uniquely for each donor, dependent on size of inoculum, length of incubation, and means by which the culture was maintained. The changing virulence of an organism and its unique growth patterns in different individuals' plasma and whole blood may explain why patients exposed to the same organisms within the same environment vary in susceptibility to clinical infection.