What distinguishes an esterase from a lipase: a novel structural approach

Esterases and lipases both hydrolyse ester bonds. Whereas the lipases display high activity towards the aggregated state of its substrate, the esterases typically show highest activity towards the soluble state of its substrate. We have compared the amino acid sequence, the 3D-structure as well as the pH-dependent electrostatic signature of selected members of the two families, for which 3D-structural information is publicly available. Lipases display a statistically significant enhanced occurrence of non-polar residues close to the surface, clustering around the active-site. Lid opening appears to strengthen this pattern further. As we have proposed earlier the active site of lipases displays negative potential in the pH-range associated with their maximum activity, typically at pH values above 8. The esterases show a very similar pattern, however, at pH values around 6 correlated with their usually lower pH-activity optimum.     

Campylobacter fetus septic arthritis: report of a case.

We report a case of septic arthritis caused by the fastidious gram-negative rod Campylobacter fetus. We suggest that the organism may be part of the endogenous flora and that the clinical infections tend to occur in compromised hosts. Our patient is the first to be described with multiple myeloma and C. fetus septic arthritis. The documented cases of culture-proven C. fetus septic arthritis reported to date have occurred in three men and one woman, all in the seventh and eighth decades of life, with a mono-articular large joint distribution. The septic arthritis always occurred in previously injured joints and curiously enough need not be associated with a toxic-appearing patient. C. fetus infections are also associated with the signs and symptoms of clinical thrombophlebitis. We stress caution in establishing this diagnosis of phlebitis on clinical evaluation only and urge differentiation of true deep vein thrombophlebitis from pseudothrombophlebitis or dissected popliteal synovial cyst. This latter diagnosis may be made non-invasively by ultrasound techniques.     

Pediatric osteomyelitis and septic arthritis: the pathology of neonatal disease

The morphologic and histologic examination of over fifty-five foci of metaphyseal/epiphyseal osteomyelitis and eleven septic joints from five cases of neonatal osteomyelitis and joint sepsis are described in detail. The severity of the bone and joint involvement varied considerably, allowing a better understanding of the pathophysiologic sequence of events in the disease in the neonatal time period. Of particular importance were (1) the multifocal nature of the disease, (2) the highly variable destruction of the growth plate (physis) by several discrete mechanisms, and (3) the invasion of the chondroepiphysis through the cartilage canal systems. Two of the cases died from respiratory complications several months following presumed successful treatment of their skeletal infections. S&pecimens showed significant growth plate damage continuing beyond the neonatal period. These findings support the need for rapid diagnosis and drainage, whenever feasible, to prevent long-term skeletal growth damage. The severity of involvement also should emphasize that this disease, especially in the neonate, is not an innocuous condition, as a recent review suggested.     

The serum IL-12:IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation

BACKGROUND: Fever during neutropenia and after neutrophil engraftment (post-engraftment fever) occurs commonly during autologous transplantation (ASCT), but infections are infrequently identified. Tests that reliably exclude infection may reduce the cost and toxicity of unnecessary diagnostic testing and empiric treatment. We assessed whether serum levels of inflammatory cytokines could distinguish infectious from non-infectious causes of fever in patients undergoing ASCT. METHODS: Serum levels of IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-12(p70), TNF-alpha and IFN-gamma were measured by sandwich ELISA at multiple pre-determined times and at the onset of the first fever during neutropenia and after neutrophil engraftment in patients with hematologic malignancies undergoing ASCT. Standard clinical criteria were used to assess for the presence of infection. RESULTS: Seventy-two febrile episodes occurred in 54 of 65 enrolled patients; 29 (40%) of the episodes occurred after neutrophil engraftment. Infections were identified as the cause of 28% and 24% of the neutropenic and post-engraftment febrile episodes, respectively. The level of IL-12 decreased and that of IL-6 increased significantly during fever because of infection, such that the IL-12:IL-6 ratio accurately excluded infection. The area under the ROC curve for the IL-12:IL-6 ratio was 0.88 (95% CI 0.79-0.97). The sensitivity, specificity, positive predictive and negative predictive values associated with a cut-off ratio of 4.1 were 95%, 75%, 60%, and 97%, respectively. DISCUSSION: The IL-12:IL-6 ratio effectively discriminates infectious from non-infectious causes of fever during ASCT. It may be useful in assessing the probability of infection in patients with post-engraftment fever.     

A pattern of protein expression in peripheral blood mononuclear cells distinguishes rheumatoid arthritis patients from healthy individuals

We compared the expression levels of proteins in peripheral blood mononuclear cells (PBMCs) of healthy control individuals to those of patients diagnosed with rheumatoid arthritis (RA) using a proteomics approach. Using two-dimensional electrophoresis we identified 18 proteins that were 2-fold or more highly expressed in patients than in controls, and 11 proteins that were 2-fold or more highly expressed in controls than in patients. Some of these differentially expressed proteins, identified by MALDI-TOF spectrometry, have previously been shown to play a potential role in the pathogenesis of RA. Hierarchical cluster analyses of the data segregated the samples into two groups, one which contained only controls and the other which contained only patients, and was used to compare the expression pattern of these 29 proteins in individual samples with the median expression pattern determined in the healthy control and in the RA patient groups. This analyses was able to predict whether a sample was derived from a rheumatoid arthritis patient or from a healthy individual, suggesting that a comparison of such protein expression patterns may be of diagnostic value.     

Leukocyte isolation by sedimentation: the effect of rouleau-promoting agents on leukocyte differential count.

The rouleau-promoting agents dextran and polyvinylpyrrolidone (PVP) were used to accelerate erythrocyte sedimentation in order to harvest the leukocyte rich plasma (LRP). The objective of the work was to determine if agent concentration or blood: agent ratio had any effect on the leukocyte differential count and if so at what agent concentration and agent:blood ratio did the LRP leukocyte differential count most closely match the whole blood leukocyte differential count. With both sedimentation agents the data clearly indicate that both parameters effect LRP differential counts and that low concentrations of sedimentation agents are most important in obtaining LRP differential counts which most closely match the whole blood differential counts.     

Report from China social and ethical influence of some pain: the causes of lower incidences of some pain syndromes in Chinese people

Western studies of national differences in pain have indicated that pain tolerance is higher in white than in Asian patients. The authors' clinical experiences in China seem to contradict this conclusion, and they have investigated the incidence or prevalence of some pain syndromes and have made comparisons with Western data. Their findings show that the incidence of most pain syndromes is lower in China than in Western countries. Hu and Fang argue that social and ethical factors have an important influence on pain tolerance. They identify four factors affecting pain tolerance in Chinese patients: (1) Chinese are less alienated from nature than are people in developed countries; (2) traditional teachings emphasize composure and rationality over emotion; (3) a state-provided health insurance system lessens anxiety; and (4) a different practice of medical ethics does not include disclosure and informed consent.     

Titanium serum levels may remain elevated despite hip revision surgery for wear-through of an acetabular component.

A 62-year-old female patient showed radiographic signs of severe linear wear of the acetabular component six years after cementless total hip arthroplasty. This suggested wear-through of the acetabular liner with secondary wear of the titanium shell. At revision surgery wear-through of both the inlay and the acetabular shell were confirmed. Despite meticulous debridement serum titanium levels remained elevated for more than 12 months. Wear-through of a polyethylene acetabular liner with secondary wear of the titanium shell can lead to increased titanium serum levels. Titanium serum levels can remain highly elevated despite revision surgery.     

Patellofemoral knee pain treatment using neuromuscular retraining of the hip musculature in an adolescent female: a case report

The purpose of this case study is to demonstrate the treatment of patella-femoral knee pain in an adolescent female athlete with emphasis on neuromuscular training of the knee and hip in synergy movement strategies. A 1.67-m, 61.5-kg, 15-year-old woman athlete reported to rehabilitation with the complaint of a 1-year history of bilateral knee pain. The patient noted that the symptoms were exacerbated with any sports-specific training. The patient played softball as an infielder. The athlete was referred by her family practice physician. After the patient was assessed, a clinical hypothesis was generated. It was thought that neuromuscular dysfunction of the hips and knees was causing faulty knee mechanics. These abnormal mechanics were presenting as patella-femoral knee pain. Initially, the athlete was assigned a home exercise program of side-lying hip abduction and lateral step-downs. At her first follow-up appointment, she noted increased symptoms that were aggravated with her home program. Upon inspecting her exercise technique, faulty step-down mechanics were contributing to her symptoms. Step-downs were discontinued, and the patient was instructed in and performed a chair squatting exercise, which was added to her home program. At her next follow-up, the patient noted being asymptomatic for 2 days. Her exercises were increased in intensity to include a Stairmaster and hip abduction and adduction on a 4-way hip machine. Eventually, over her treatment course, perturbation and proprioceptive training were initiated. By the sixth visit, the patient reported no symptoms and felt comfortable with self-management. A phone interview 3 months later indicated that the patient had no recurrent symptoms and was participating in sports without difficulty. This case demonstrates effectiveness of using hip and knee joint synergy to treat patella-femoral pain (PFP). The use of this synergy promotes proper patella–femoral alignment and improved knee mechanics. This case also is unique in the lack of physical agents and taping used to improve the patient's condition. It reinforces how exercise technique can carry over to functional athletic activities. This study provides a case for the use of hip and knee mechanical retraining in the treatment of PFP in adolescent female athletes who do not exhibit abnormal foot mechanics in weight bearing. It is important that sports medicine professionals be aware of these treatment options and are able to use them to correct these deficits in order to facilitate return to training and competition as quickly and safely as possible.     

The physiology of leukocyte recruitment: an in vivo perspective

The mechanisms of leukocyte recruitment have been studied extensively in vitro and have shed light on the basic molecular structure-function relationship of adhesion and signaling molecules involved in this essential immune response. This review will summarize how these in vitro observations extend to leukocyte behavior in inflamed blood vessels in the microcirculation. We highlight physiological results that might not have been predicted from in vitro systems. Special attention is placed on the physiology of rolling, adhesion, and intralumenal crawling in blood vessels. The importance of the glycocalyx, secondary tethers, shear, and the microenvironment are discussed. Docking structures forming rings of adhesion molecules together with a novel endothelial dome-like structure in vivo during transmigration are highlighted. Transcellular and paracellular emigration out of inflamed blood vessels is also discussed. The last section highlights leukocyte recruitment in some organs that do not always follow the accepted paradigm of leukocyte recruitment.     

Further evidence validating adjuvant arthritis as an experimental model of chronic pain in the rat

The experiments described here were aimed at further validating adjuvant arthritis as an animal model of chronic pain. It was found that the relative oral intake of a 0.008 mg/ml solution of fentanyl was higher in arthritic than in normal control rats; this difference was predicted by the notion that the analgesic effect of a substance may reinforce its intake in animals exposed to pain, more so than in normal pain-free animals. It was also found that body weight decreases and that vocalizations of aggregated rats increase as a result of the challenge; these effects suggest that the vegetative signs and the behavioral irritability which are characteristic of chronic pain in humans, also occur in arthritic animals. The pain which thus seems to be associated with adjuvant arthritis was estimated to have its onset on days 10–11, to peak on days 18–21, and to terminate on days 35–40 after inoculation with $\text{Mycobacterium butyricum}$.