Antimicrobial technology in orthopedic and spinal implants

Infections can hinder orthopedic implant function and retention.Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion.Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems,material science,immunology,and polymer chemistry are in development and early clinical use.This review outlines orthopedic implant antimicrobial technology,its current applications and supporting evidence,and clinically promising future directions.     

17 alpha-O-(aminoalkyl)oxime derivatives of 3 beta,14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane as inhibitors of Na(+),K(+)-ATPase at the digitalis receptor.

The synthesis and binding affinities to the digitalis Na(+),K(+)-ATPase receptor of a series of 3 beta,14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane derivatives bearing a 17 alpha-(aminoalkoxy)imino chain are reported; some derivatives were also studied for their inotropic activity. Our recently proposed model of interaction of molecules with the digitalis receptor was used to design these compounds. On that basis, the possibility to design novel potent inhibitors of Na(+),K(+)-ATPase without being constrained by the stereochemistry of the classical digitalis skeleton in the D-ring region was predicted. The binding affinities of the most potent compounds in the two series, (EZ)-17 alpha-[2-[(2-aminoethoxy)imino]ethyl]-5 beta-androstane-3 beta,14 beta-diol (6f) and (EZ)-3 beta-hydroxy-17 alpha-[2-[(2-aminoethoxy)imino]ethyl]-14,15-seco-5 beta-androstan-14-one (24c) are higher than that of the potent natural compound digitoxigenin, despite the unusual alpha-exit of the substituent in position 17 of 6f or the disruption of the D-ring in 24c. These results further support the validity of our recently proposed model of binding at the digitalis receptor. Results of the inotropic tests on guinea pig atrium deserve further investigation on the pharmacological profile of these derivatives.     

Whiplash injury and oculomotor dysfunctions: clinical–posturographic correlations

Oculomotor dysfunctions are hidden causes of invalidity following whiplash injury. Many patients with whiplash injury grade II present oculomotor dysfunctions related to input disturbances of cervical or vestibular afferents. We used static posturography to investigate 40 consecutive patients with whiplash injury grade II and oculomotor dysfunctions. We demonstrated a relation between length and surface of body sway: the surface value (A) was higher than the length value (L) and this led to an open graph of body sway in the statokinesigram. Oculomotor rehabilitation can resolve the impairment of vestibular function but if therapy is delayed or the patient has been wearing an orthopaedic neck collar, more therapeutic sessions are required. In conclusion, without rehabilitation of the oculomotor muscles other therapies are not sufficient to recover the impairment caused by whiplash injury.     

MP-Link cementless distal fixation modular prosthesis for revision total hip arthroplasty

The aseptic loosening of the femoral stem may require different treatments due to the complex problems related to the bone resorption (qualitatively and quantitatively): a minimum bone stock loss may result in a periprosthetic resorption that is so severe to make the fixation of the revision prosthesis extremely difficult. The revision surgery of a loosened hip prosthesis is often characterized by a complex reconstruction due to such severe loss of femoral bone tissue. We illustrate our experience with MP-Link modular stem (Waldemar Link, Hamburg, Germany) in cases of severe bone loss of the metaphyseal area and of the proximal third of the femoral shaft, assessing the technological developments (materials and design) over the years and examining the pros and cons of cementless distalfixation modular stems versus the traditional Wagner's stem. Received: 3 May 2001/Accepted: 14 January 2002     

Captopril therapy in severe hypertension: effects of intravenous administration.

In 10 severe hypertensives the effects of intravenous administration of scalar doses of captopril were evaluated. The behaviour of blood pressure, heart rate, electrocardiographic pattern and left ventricular (LV) diastolic function, in basal condition (T0) and after 60 min of captopril infusion (T60), were analysed. Diastolic performance was assessed by pulsed wave Doppler echocardiography, evaluating transmitral peak flow velocities in early diastole (PEDV), late diastole (PLDV) and the PEDV/PLDV ratio. All patients showed an increase in LV mass (assessed by M-mode echocardiography) and altered diastolic performance, documented by high PLDV and low PLDV/PEDV ratio values. Clinical, haematological, urinary and biochemical data were also assessed for possible side effects. Captopril significantly reduced BP in 7 out of the 10 patients. Supine BP decreased from 212 +/- 15.3/126 +/- 5.6 to 171 +/- 17.7/98 +/- 11.8 mmHg (T0 vs. T60 P less than 0.0001). No electrocardiographic abnormality was observed during the study. The goal of antihypertensive effect was reached at 40-50 min after the onset of captopril therapy. Heart rate showed a small but constant decrease (from 76 +/- 7.7 to 72.8 +/- 5.7 beats/min, T0 vs. T60, P less than 0.05). Side effects of intravenous captopril were always mild and transient; no severe hypotension as 'first dose effect' was observed in our study. The echocardiographic data showed a significant decrease in LV end-systolic dimension after captopril infusion, while left atrial, LV diastolic dimension and fractional shortening remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load

The aim of this study was to simultaneously measure in vivo volumes of gray matter (GM), normal white matter (WM), abnormal white matter (aWM), and cerebro-spinal fluid (CSF), and to assess their relationship in 50 patients with relapsing-remitting multiple sclerosis (RR-MS) (age range, 21-59; mean EDSS, 2.5; mean disease duration, 9.9 years), using an unsupervised multiparametric segmentation procedure applied to brain MR studies. Tissue volumes were normalized to total intracranial volume providing corresponding fractional volumes (fGM, faWM, fWM, and fCSF), subsequently corrected for aWM-related segmentation inaccuracies and adjusted to mean patients' age according to age-related changes measured in 54 normal volunteers (NV) (age range 16-70). In MS patients aWM was 23.8 +/- 29.8 ml (range 0.4-138.8). A significant decrease in fGM was present in MS patients as compared to NV (49.5 +/- 3.2% vs 53.3 +/- 2.1%; P < 0.0001), with a corresponding increase in fCSF (13.0 +/- 3.8% vs 9.1 +/- 2.4%; P < 0.0001). No difference could be detected between the two groups for fWM (37.5 +/- 2.6% vs 37.6 +/- 2.2%). faWM correlated inversely with fGM (R = -0.434, P < 0.001 at regression analysis), and directly with fCSF (R = 0.473, P < 0.001), but not with fWM. There was a significant correlation between disease duration and EDSS, while no relationship was found between EDSS or disease duration and fractional volumes. Brain atrophy in RR-MS is mainly related to GM loss, which correlates with faWM. Both measures do not appear to significantly affect EDSS, which correlates to disease duration.     

Uncoordinated expression of fibrinogen compared with thrombospondin and von Willebrand factor in maturing human megakaryocytes

The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source.     

Extended long-term culture reveals a highly quiescent and primitive human hematopoietic progenitor population

Long-term culture-initiating cells (LTC-IC) are hematopoietic progenitors able to generate colony-forming unit-cells (CFU) after 5 to 8 weeks (35 to 60 days) of culture on bone marrow (BM) stroma and represent the most primitive progenitors currently detectable in vitro. We have recently reported that long-term cultures initiated with CD34+CD38- cells from BM or cord blood are able to continue generating CFU for at least 100 days, ie, beyond the standard LTC-IC period. In this report, single-cell cultures from cord blood and retroviral marking of cord blood and BM were used to study whether the subpopulation of CD34+CD38- cells able to generate CFU beyond 60 days ("extended long-term culture-initiating cells" or ELTC-IC) are functionally distinct from LTC-IC in terms of timing of initial clonal proliferation and generative capacity. All cord blood LTC-IC formed clones of greater than 50 cells by day 30. In contrast, cord blood ELTC- IC proliferated later in culture, 50% forming clones after day 30. Although efficient retroviral marking of LTC-IC was seen (25% to 45%), marking of ELTC-IC was inefficient (< 1%), consistent with a more quiescent progenitor population. There was a positive correlation between time of clonal proliferation and generative capacity. ELTC-IC generated threefold to fourfold more progeny than did LTC-IC (P < .002). These studies show that there is a functional hierarchy of progenitors in long-term culture which correlates with their level of quiescence. By extending the LTC-IC assay, a more primitive progenitor may be studied that may be functionally closer to the human long-term repopulation stem cell in vivo.     

Usefulness of Rehabilitation in Patients with Rotator Cuff Calcific Tendinopathy after Ultrasound-Guided Percutaneous Treatment

Objective

To evaluate the efficacy of a specific rehabilitation program for patients in whom ultrasound-guided percutaneous treatment (UGPT) was performed for rotator cuff calcific tendinopathy (RCCT).

Subjects and Methods

In this prospective observational study, 86 patients (22 males and 64 females) with shoulder calcific tendinopathy treated with UGPT were enrolled. At the end of the procedure, a corticosteroid injection into the subacromial-subdeltoid bursa was performed. The patients were then asked to follow a specific rehabilitation protocol (2 times/week for 5 weeks) that focused on mobility, strength and function. At baseline and after 6 weeks, clinical parameters, visual analog scale (VAS) and Constant-Murley scale (CMS) scores and ultrasound (US) features were collected.

Results

The mean age of the patients was 48.9 ± 8.4 years and their mean BMI was 22.7 ± 2.1. Considering the whole cohort, the treatment was effective, with a significant decrease in the VAS score and an improvement in the CMS score. Thereafter, on the basis of the compliance to the rehabilitation program (by self-report), 53 and 33 patients were included in the rehabilitation group (Rehab group; performed exercises ≥2 times/week) and the No Rehab group (performed exercises <2 times/week), respectively. The comparison between the groups showed that the subjects who performed the exercises regularly had better results in terms of pain and functional recovery, and less associated diseases (e.g. adhesive bursitis and tenosynovitis of the long head of the biceps) than those who were less compliant with the program.

Conclusions

UGPT, followed by a specific postprocedure rehabilitation program, was an effective treatment for RCCT.Key Words: Rotator cuff calcific tendinopathy, Rehabilitative treatment, Ultrasound