Safety of a new conjugate meningococcal C vaccine in infants.

BACKGROUND: Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999. There has been extensive professional and public interest in their efficacy and safety. AIM: To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine. METHODS: A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine. RESULTS: There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial.

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.

Microbiologic evaluation of needleless and needle-access devices.

OBJECTIVE: This study was carried out to determine whether needleless intravenous access devices are more likely to allow microorganisms to enter the fluid pathway than intravenous needle-access devices. METHODS: A laboratory study was conducted with two needleless and one intravenous needle-access devices and Enterococcus faecium as a bacterial challenge. Inocula of E. faecium were prepared on the basis of the numerical estimates of 1000 to 10,000 colony-forming units (CFU)/cm2 of bacterial flora on dry regions of skin (arms, legs, and hands). The septum of each access device was inoculated with 10 to 20 microliters of a 10(4) to 10(5) CFU/ml challenge suspension, which was allowed to dry on the surface of the septum. In the first part of the experiment, the needleless or needle-access cannula of each device was used to puncture the corresponding septum without previously disinfecting the top of the septum. In the second part, the contaminated septum was punctured after disinfecting the septum with a 70% isopropyl alcohol wipe. After each puncture, trypticase soy broth was flushed through the fluid pathway of the intravenous access device, collected, and cultured by the membrane filtration technique. The septum of each injection-site cap and the needleless or needle-access cannula were sampled with sterile premoistened swabs. Swabs were cultured on blood agar plates. RESULTS: The rate of fluid pathway contamination was 100% (40/40) for one of the needleless intravenous access devices and 80% (20/25) for the other when septa were contaminated with E. faecium and not disinfected before puncture. The rate for the intravenous needle-access device was 72% (18/25). When the septa of the three different devices tested were disinfected with 70% isopropyl alcohol, E. faecium was isolated on only one septum from all devices tested in part two (1/74, 1.3%). CONCLUSIONS: These laboratory studies demonstrate that there is no statistically significant difference in the rate of fluid pathway contamination between needleless and intravenous needle-access devices. However, if the septa of either needleless or needle systems are not disinfected before puncture, a high rate of fluid pathway contamination may occur.

Bloodstream infections associated with a needleless intravenous infusion system in patients receiving home infusion therapy.

OBJECTIVE: To determine risk factors for bloodstream infections (BSIs) in an outbreak among patients receiving home intravenous infusion therapy. DESIGN: Case-control and retrospective cohort studies. SETTING: Home health agency. PATIENTS: Patients receiving home intravenous infusion therapy from Rhode Island Home Therapeutics (RIHT) from January through December 1993. MAIN OUTCOME MEASURE: Development of primary BSI. METHODS: We compared patients with BSI (ie, case patients) with randomly selected noninfected RIHT patients receiving intravenous therapy, conducted a cohort study of all RIHT patients receiving intravenous therapy via a central venous catheter (CVC), and conducted a culture survey of injection cap luminal fluid. RESULTS: Case patients were more likely than controls to have had therapy via a CVC (11/11 vs 14/32; odds ratio [OR] undefined; P < .001) or total parenteral nutrition and intralipid therapy (TPN/IL) (9/11 vs 3/32; OR, 43.5; 95% confidence interval [CI], 4.9 to 510.0). Among RIHT patients with CVCs, risk factors for BSI were receipt of TPN/IL (9/35 vs 2/67; rate ratio [RR], 8.6; 95% CI, 2.0 to 37.7) or use of a needleless infusion system (10/41 vs 1/61; RR, 14.9; 95% CI, 2.0 to 111.8). Only the combination of both exposures was significantly associated with development of a BSI (P < .001). Luminal fluid from injection caps of needleless devices was significantly more likely to be culture positive than fluid from protected-needle devices (5/23 vs 0/18; RR undefined; P = .04). CONCLUSIONS: Our data suggest that a needleless device used for TPN/IL was associated with increased risk of BSI when injection caps were changed every 7 days.

The effects of non-weight-bearing and limited motion on the tensile properties of the meniscus.

Recent clinical studies have suggested that many of the complications of prolonged immobilization after knee surgery can be prevented by permitting early motion while minimizing loading of healing tissues. The purpose of this study was to determine the effects of such a regimen on the tensile properties of the meniscus. The right knee of 10 skeletally mature sheep received a sham operation after which the hindlimb was placed in a harness that prevented weight bearing while permitting limited knee motion. The left knee served as the nonoperated control. Twelve weeks after surgery, paired specimens from the medial meniscus of each limb were tested in tension with the load parallel to the circumferentially oriented collagen fibers. No significant differences in the modulus, tensile strength, and ultimate strain between treated and control medial menisci were identified. Our data thus suggest that preventing weight bearing while permitting even limited motion of the knee will prevent any detrimental effect on the tensile properties of the meniscus in the circumferential direction.

Effects of an in-substance conduit with injection of a blood clot on tears in the avascular region of the meniscus.

The purpose of this study was to test the hypothesis that healing of a stable tear in the avascular region of the meniscus occurs when a horizontal conduit, extending from the periphery to the defect, is filled with an exogenous fibrin clot. In 6 sheep a full-thickness laceration was made in the lateral meniscus, and autologous blood clot was then injected into the conduit. Three animals in the control group received identical meniscal tears but no additional treatment. Casting and a harness prevented weight-bearing and maintained the knee in a flexed position. Twelve weeks after the operation histologic examination revealed only partial healing in one animal. In both the experimental and control groups increased numbers of dividing chondrocytes on either side of the tear were seen. We conclude that an in-substance conduit in combination with the injection of a blood clot is not sufficient to facilitate complete healing of a tear within the avascular region of the lateral meniscus of the sheep when the knee is immobilized only with a harness.

Effects of abrasion therapy on tears in the avascular region of sheep menisci.

This study was designed to test the hypothesis that abrasion of the parameniscal synovium aids healing of a stable tear in the avascular region of the meniscus in a sheep model. In six sheep, a 5-7-mm longitudinal full-thickness tear was made in the avascular inner half of the anterior part of the lateral meniscus. The parameniscal synovium was abraded superiorly and inferiorly from the meniscus periphery to the lesion. Three animals in a control group received identical meniscal tears but no abrasion treatment. A harness prevented weight bearing and maintained the knee fully flexed after surgery. Twelve weeks after the operation, no healing was seen in any tears. Histologic examination revealed in both groups increased numbers of dividing chondrocytes on either side of the tear. In the test group, several layers of fibroblasts, which appeared in two menisci to derive from the upper meniscal surface, were seen covering both cut surfaces of the tear. It is concluded that the distance from the periphery to the defect is too far for abrasion therapy to stimulate sufficient cellular ingrowth to facilitate repair of tears in the avascular region of the meniscus.

Experimental models to promote healing of tears in the avascular segment of canine knee menisci.

Longitudinal tears were created in canine lateral menisci and techniques were applied to induce healing by removal of a core of tissue from the periphery of the meniscus to the tear or by implantation of a vascularized synovial flap into the tear. The meniscal tears did not heal in knees that were not immobilized, and they healed poorly and sporadically in knees that were immobilized in a cast but bore some weight. However, a higher percentage of tears that were treated by the core-removal or synovial-flap technique healed when the knee was firmly immobilized and weight-bearing was prevented by the use of an external skeletal fixator across the joint for eight to twelve weeks. Neovascularization and access to a source of reparative cells appear to be important in the healing process.

Intraarticular pressure during continuous passive motion of the human knee.

Intraarticular pressure (IAP) was continuously monitored during continuous passive motion (CPM) of five normal and 11 abnormal human knees using a new fiberoptic, transducer-tipped Camino catheter. IAP varied in a consistent hysteresis pattern in the normal knees, with subatmospheric pressures recorded at intermediate angles of joint flexion. A similar pattern was recorded in the abnormal knees without cruciate ligament pathology, whereas considerable variability was noted in the knees with cruciate ligament abnormality. IAP was lower in the extension to flexion than in the flexion to extension portion of the CPM cycle, providing evidence of intraarticular fluid flow during portions of the CPM cycle. IAP changes were consistent with "physiologic compartmentation" within the knee at extremes of joint position. Capsular viscoelastic changes and/or synovial fluid volume changes were observed during CPM. The therapeutic mechanism of continuous passive motion may be related to cyclic variation of the intraarticular pressure.

Kappa Delta Award paper. Tissue fluid pressures: from basic research tools to clinical applications.

The two basic research tools developed to measure tissue fluid pressure (wick catheter) and osmotic pressure (colloid osmometer) have undergone extensive validation and refinement over the past 20 years. Using these techniques, basic science investigations were undertaken of edema in Amazon reptiles, pressure-volume relations in animals and plants, adaptive physiology of Antarctic penguins and fishes, edema in spawning salmon, tissue fluid balance in humans under normal conditions and during simulated weightlessness, and orthostatic adaptation in a mammal with high and variable blood pressures--the giraffe. Following and sometimes paralleling this basic research have been several clinical applications related to use of our colloid osmometer and wick technique. Applications of the osmometer have included insights into (a) reduced osmotic pressure of sickle-cell hemoglobin with deoxygenation and (b) reduced swelling pressure of human nucleus pulposus with hydration or certain enzymes. Clinical uses of the wick technique have included (a) improvement of diagnosis and treatment of acute and chronic compartment syndromes, (b) elucidation of tissue pressure thresholds for neuromuscular dysfunction, and (c) development of a better tourniquet design for orthopaedics. This article demonstrates that basic research tools open up areas of basic, applied, and clinical research.

Regional nutrition and cellularity of the meniscus. Implications for tear and repair.

The knee menisci are relatively avascular and must rely to a large degree on synovial sources of nutrition. Lack of nutrition may lead to degenerative changes and may inhibit any potential repair capabilities of the menisci. Continuous passive motion applied to the knee stimulates greater activity and/or transport of nutrients to the meniscal fibrochondrocytes. However, in an avascular model, solutes within the synovial fluid are lost by their convective transport from the joint. Regional differences in transport of a low molecular weight nutrient like sodium sulphate exist such that cells in the central core region of the meniscus are poorly supplied with nutrients by the synovial fluid and/or are less active. These conditions may be the cause of a relatively high incidence of degenerative changes in the central core region.

Differential response of the dog quadriceps muscle to external skeletal fixation of the knee.

The change in muscle fiber size and fiber percentage was studied in three heads of the dog quadriceps following 10 weeks of immobilization using an external skeletal fixator. Muscle biopsy morphometric analysis revealed that muscle fiber atrophy was greatest for the vastus medialis and least for the rectus femoris. The atrophic response for type 1 fibers was, in order from most to least atrophied: VM greater than VL greater than RF, whereas for type 2 fibers the corresponding order was VM = VL greater than RF. An increase in connective tissue was also observed for all muscles. These results are discussed in terms of skeletal muscle architecture, initial fiber-type distribution, and level of use. As a result, predictions are made as to the muscles that are most vulnerable to disuse atrophy, namely the postural muscles that contain a relatively large proportion of slow muscle fibers and cross a single joint. Conversely, those that are least susceptible to atrophy are those that are not used as postural muscles, that cross multiple joints, and that are predominantly composed of fast muscle fibers.

Increased transsynovial transport with continuous passive motion.

Thirteen freshly killed immature rabbits were used to study the effect of continuous passive motion (CPM) on regional nutritional pathways of the medial and lateral menisci and the transport of a solute from synovial fluid to the patellar tendon. A bolus of 35SO4 was injected into each knee joint cavity. The right knee underwent CPM for 1 h, whereas the left knee was immobilized (rest extremity). Both knees were then rapidly resected and immediately frozen. The medial and lateral menisci were removed and sectioned into anterior, middle, and posterior thirds for Group 1 animals; in Group 2 animals a portion of patellar tendon was harvested. Radioactivity as counts per minute per milligram of tissue was counted in a scintillation counter. The posterior portion of the lateral meniscus in the rest extremity had significantly higher uptake than the extremity that underwent CPM (p less than 0.001). In the extremity at rest, the posterior third of the lateral meniscus had a significantly higher uptake than that of the middle third (p = 0.04). In Group 2 rabbits, the patellar tendon of the knee undergoing CPM had significantly higher uptake as compared with the patellar tendon of the knee at rest (p = 0.02). These results indicate that diffusion from synovial fluid to meniscal cells is an important mechanism of transport for low-molecular-weight nutrients such as sulfate; CPM does not facilitate this mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutrition of the anterior cruciate ligament. Effects of continuous passive motion.

Twelve freshly killed mature male rabbits were used to study the effects of continuous passive motion (CPM) on regional and overall nonvascular nutritional pathways of the anterior cruciate ligament (ACL). One hundred fifty microcuries of 35sulphate was injected intraarticularly into each knee joint. The right knee underwent CPM for 1 hour, while the left knee remained immobilized. Both knee joints were then isolated and immediately frozen. The ACLs were removed while still mostly frozen, and sectioned into anterior, middle, and posterior thirds for the six rabbits in Group 1, and proximal, middle, and distal thirds for the six rabbits in Group 2. In addition, quadriceps tendon samples were harvested from each limb of three rabbits. After appropriate processing, all samples were counted in a scintillation counter, and counts per minute per milligram of tissue were calculated. There was significantly higher uptake in rest extremity ACLs compared to CPM extremity ACLs (P = 0.0001). No significant difference was demonstrated in regional uptake comparing respective thirds of the ACL in either Group 1 or Group 2. Quadriceps tendon uptake trended higher in the limbs exposed to CPM compared to those maintained at rest (P = 0.14). The ACL uses diffusion as a primary nutrient pathway. CPM does not increase nutrient uptake by the ACL in this avascular model, but CPM may facilitate transport of metabolites out of the joint. No regional differences in uptake within the ACL occurred in either group.

Synovial cysts of the hip joint and iliopsoas bursitis: a spectrum of imaging abnormalities.

Synovium-related soft tissue disease around the hip constitutes a spectrum ranging from isolated iliopsoas bursitis to pure articular synovial herniations without bursal involvement. The clinical, pathologic, and radiographic features of these entities are discussed as they pertain to the variety of underlying disorders which predispose to their occurrence. Nine case reports are utilized to illustrate the variable clinical and radiographic presentations which may be encountered. Based upon these cases as well as those in the literature, an imaging algorithm has been developed which should eliminate unnecessary studies and allow prompt and accurate diagnosis.

Computed and conventional arthrotomography of the glenohumeral joint: normal anatomy and clinical experience.

The glenohumeral joint was studied in 25 cadavers and 136 patients using computed arthrotomography (CAT) and conventional arthrotomography (AT) to assess shoulder instability. Cadaver shoulders were injected with air or latex, sectioned with a band saw, and normal articular anatomy outlined. CAT was performed in 81 patients and characterized the glenoid labrum as normal, abnormal, or detached in 38 of the 44 patients who had surgery or arthroscopy (sensitivity, 96%; accuracy, 86%). Hill-Sachs defects were seen in 20 out of 29 patients with anterior labral abnormalities, while bicipital tendon abnormalities were evident on CAT in 6. Of 55 patients who had AT, the status of the labrum was clarified in 13 of the 16 patients who had surgery or arthroscopy (sensitivity, 86%; accuracy, 81%). Both methods can characterize the labrum; however, CAT is more comprehensive and appears ideal for both detection of Hill-Sachs defects and imaging the bicipital tendon. CAT requires less technical expertise and radiation than AT and is tolerated better by patients in pain.

Shoulder impingement syndrome: radiographic evaluation.

The impingement syndrome is an important source of shoulder pain that occurs when the bony and soft-tissue structures of the superior aspect of the shoulder encroach upon the coracoacromial ligamentous arch during abduction of the arm. Subacromial bursitis, bicipital tendinitis, and rotator cuff disruptions are common sequelae of this abnormality. The presence of bony excrescences arising from the anteroinferior aspect of the acromion and of flattening and sclerosis of the greater tuberosity of the humerus is an important plain radiographic sign of the impingement syndrome. Fluoroscopy, shoulder arthrography, subacromial bursography, and bursotomography are fundamental diagnostic imaging modalities in this disorder.