Perplexities of pertussis: recent global epidemiological trends and their potential causes.

Recent much-publicized increases in pertussis case reports in some countries with high vaccine coverage have raised concerns about its current and future control. The ubiquity of this trend, however, remains unexamined. In an attempt to paint a global picture, we used case counts to determine which countries experienced statistically significant trends in incidence over the past two decades and to map changes in incidence during this period. These data reveal that pertussis resurgence is not a universal phenomenon. The heterogeneity in incidence trends, even in countries with superficially similar demography, socioeconomic conditions and vaccination programmes, is striking and requires explanation. In this opinion piece, we review and assess the multifaceted proposed explanations incorporating evolution, population dynamics, and the details of immunization programmes. While we do not solve the riddle that is pertussis epidemiology, we highlight critical aspects that are likely to hold the key to understanding its worldwide epidemiology.

2009 Melbourne metropolitan sewerage strategy: a portfolio of decentralised and on-site concept designs.

The bulk and retail water companies of the greater Melbourne area are developing the 2009 Metropolitan Sewerage Strategy to provide sustainable sewerage services to 2060. The objective of the strategy is to establish long term principles and near term actions to produce a robust sewage management system for Melbourne. Melbourne's existing sewerage system is largely centralised and discharges to two major treatment plants. Several small satellite treatment plants service local urban areas generally more distant from the centralised system. Decentralised and on-site wastewater systems are options for future sewage management and could play a role in local recycling. A portfolio of 18 on-site and decentralised concept designs was developed, applicable to the full range of urban development types in Melbourne. The concepts can be used in evaluation of metropolitan system configurations as part of future integrated water cycle planning. The options included secondary and tertiary treatment systems incorporating re-use of water for non potable uses, urine separation, black and greywater separation and composting toilets. On-site and cluster treatment systems were analysed. Each option is described by its indicative capital and operating costs, energy use and water and nutrient balances. This paper summarises and compares the portfolio mix of decentralized and on-site options in Melbourne's context.

The effect of hypoxia on monoamine levels in discrete regions of aged rat brain.

Aged rats were exposed to 10% oxygen for 1, 13, and 36 hr. Norepinephrine levels in cerebral cortex, hypothalamus, hippocampus, midbrain, cerebellum, pons-medulla and dopamine levels in striatum were determined after each exposure. While there was no significant change in monoamine levels in brain regions after 2 hr, norepinephrine concentration in hypothalamus and midbrain decreased significantly after 13 hr of hypoxia. After 36 hr in a hypoxic environment, levels of the monoamines in brain regions were similar to the controls. This would suggest NE metabolism is most vulnerable to hypoxia in two regions of the aged brain. The precise mechanism of these changes is unknown, but they suggest both a vulnerability and an adaptive recovery of central adrenergic metabolism by the aged brain under hypoxia.

Using a monoclonal antibody to identify patients with type I and type II von Willebrand's disease.

Three monoclonal antibodies produced against vWF:Ag by conventional hybridoma technique did not inhibit factor VIII coagulant activity (F. VIII:C) but did inhibit VIII ristocetin cofactor activity. The antibodies were used in an indirect competitive ELISA for quantifying von Willebrand's antigen (vWF:Ag) and compared with values obtained by the Laurell technique using commercial antibody by means of a ratio: ELISA/Laurell. For one monoclonal BD2-CC9, vWF:Ag values obtained in the two assays were in good agreement for normal and hemophilia A plasmas (normal, n = 19, ratio = 1.13 +/- .17, hemophilia A, n = 10, ratio = 0.91 +/- .15). However, type II vWD patients had a disproportionately low value of vWF:Ag with the ELISA. Use of the ratio normalized the difference among individual plasma values and allowed a significant separation of type II vWD plasma (n = 9, ratio = 0.46 +/- .19) from normal plasma (p = .0001) and type I vWD plasma (n = 8, ratio = 1.52 +/- .34) from type II vWD plasma (p = .0003) using BD2-CC9. Although the sample size was small, the greater degree of discrimination among the vWD plasmas tested with BD2-CC9 (compared with the other two antibodies [CA3-AE4, CC6-BG10]) suggests that this antibody may recognize conformational epitopes that reflect the degree of multimeric polymerization of the vWF molecule rather than simply recognize a decreased number of antigenic sites in a basic subunit. BD2-CC9 may be valuable in investigating the various types of vWD and/or the process of polymerization of this complex protein.

Reduced anterior tibial translation associated with adaptive changes in the anterior cruciate ligament-deficient joint: goat model.

Adaptive changes in the menisci and adjacent posterior capsule were documented within anterior cruciate ligament-deficient knee (stifle) joints in the goat model. These physical changes in the menisci and capsule developed over time and were associated with reduction in the initial (time zero) abnormal anterior tibial translation following transection of the anterior cruciate ligament. At 50 N of applied force, the normal goat knee joint has a total anterior-posterior translation of 0.6+/-0.1 mm (+/- SEM) at 45 degrees of flexion and 0.3+/-0.1 mm at 90 degrees. The translation immediately after transection (time zero) with 50 N of force was 8.2+/-0.5 mm at 45 degrees and 4.9+/-0.9 mm at 90 degrees. Within 8 months after transection and at 50 N of force, the treated knees had reduced translation values of 5.3+/-0.6 mm at 45 degrees of flexion and 2.9+/-0.5 mm at 90 degrees, or 35 (p<0.001) and 40% reductions, respectively, compared with the values at time zero. Magnetic resonance images of the ligament-deficient stifle joints, as well as gross measurements and image analysis after dissection, consistently demonstrated increases in cross-sectional area and volume of the menisci compared with the contralateral controls. These secondary changes were most pronounced in the posterior portion of the medial menisci, and histologic evaluation demonstrated hypercellularity with the accumulation of poorly organized collagen, reduced safranin O staining (proteoglycan matrix synthesis), a thickened capsule and capsule attachment, and increased vascularity at the meniscal capsule interface.

Assessment of donor cell and matrix survival in fresh articular cartilage allografts in a goat model.

The long-term survival of allografts of articular cartilage has been proposed to be dependent on the survival of the cells that maintain the unique structural and material properties of the allograft. In this study, we assessed cell survival in 24 fresh articular cartilage allografts of the medial plateau in a Spanish-goat model. A DNA-probe technique was used to distinguish clearly between DNA from donor (allograft) and host cells. The intraarticular survival of viable allograft chondrocytes in the transplanted articular cartilage started to diminish as early as 3 weeks after transplantation; however, there was considerable variation in the amount of donor cell DNA detected in the allografts at 6 and 12 months following transplantation. This contrasts with our experience with fresh allografts of ligament, tendon, and meniscus, in which no donor DNA was detected 4 weeks after transplantation. DNA from host cells was present in all articular cartilage allografts, as evidenced by detectable unique host DNA patterns. Histological and histochemical assays showed that none of the transplants demonstrated normal structure and composition at 1 year after transplantation. The grafts in which large quantities of donor DNA were present appeared grossly superior to those with no or reduced remaining demonstrable donor DNA.

The correlation between anterior-posterior translation and cross-sectional area of anterior cruciate ligament reconstructions.

Total anterior-posterior translation is commonly used to assess the integrity of the cruciate ligaments and the success of reconstructive surgery. The purpose of this study was to determine, after surgical reconstruction of the anterior cruciate ligament with a biological graft, if total anterior-posterior translation correlated with graft length, cross-sectional area, or mechanical properties. These factors were investigated by analyzing data from three previous studies. These studies involved replacement of the anterior cruciate ligament in cynomolgus monkeys and goats, with free and vascularized patellar tendon autografts and both patellar tendon and anterior cruciate ligament allografts. Data were available at time periods of 6 and 12 months after surgery. We found statistically significant inverse correlations between the amount of anterior-posterior translation and cross-sectional area of a graft at the time of sacrifice. The Pearson correlation coefficients ranged from -0.966 (p < 0.002) to -0.830 (p < 0.05). We hypothesize that these correlations result from the following mechanism: the increased anterior translation reflects a slack graft; a slack graft is stress shielded by other structures about the knee; the reduced in vivo stresses on the graft modulate cellular metabolism in a way that over time produces a small cross-sectional area.

Iliotibial band syndrome in distance runners.

Iliotibial band syndrome was diagnosed in 48 of 1030 runners treated for lower extremity musculoskeletal complaints. Most athletes had been running 20 to 40 miles a week for one year or longer and had significantly changed their distance, speed, terrain, surface, and/or shoes before the onset of symptoms. Symptoms often persisted for 2 to 6 months. All runners were treated conservatively with rest, stretching, reduced distance, anti-inflammatory medications, local cortisone injections and/or orthoses.

Lacerations of the flexor hallucis longus in the young athlete.

Of ten patients with lacerations of the flexor hallucis longus tendon, nine were athletically inclined. In four, the laceration was not repaired and no disability was evident. A functioning flexor hallucis longus, therefore, does not seem to be essential for good push-off and balance in running sports. If both the flexor hallucis brevis and the flexor hallucis longus are lacerated and reconstitution of the longus is not possible, the brevis should be repaired, suturing the distal segment of the longus to brevis to prevent hyperextension deformity of the metatarsophalangeal joint. Hypersensitivity of the scar due to associated nerve injury is a frequent complication associated with laceration of the flexor hallucis longus.

Tears of the anterior cruciate ligament in young athletes.

During a meniscectomy, thirty competitive athletes who were less than thirty years old were found to have a non-functional or absent anterior cruciate ligament. Preoperative examination without anesthesia had revealed minimum to mild anterior instability without a positive pivot-shift or jerk test. They all had a meniscectomy without reconstruction of the ligament and all were followed for up to four years (average, 2.6 years). Twenty-five (83 per cent) returned to full athletic activity. All had relief of the symptoms of the meniscal lesion and improved significantly, but six progressed to moderate anterior instability with a positive pivot-shift and jerk test. Nevertheless, four of the six were able to resume unrestricted athletic activity.

Fatigue fracture: the basic lesion is inthmic spondylolisthesis.

The defect in the pars interarticularis in spondylolysis and spondylolisthesis is most often the result of repeated trauma, stress, and factors other than acute fracture. These fatigue fractures develop early in life, may have a strong hereditary basis, and most often represent incidental roentgenographic findings. Attention should be given to the youngster or adolescent with low-back pain and paraspinal muscle spasm. If these patients are followed closely, the incidence of pars interarticularis defect is higher than appreciated. The lesion in some of these individuals may progress to significant vertebral slipping. If the developing defect is recognized early, treatment can be quite satisfactory.

Characterization of the repair tissue after removal of the central one-third of the patellar ligament. An experimental study in a goat model.

UNLABELLED: The purpose of this study was to characterize the repair tissue that develops after removal of a portion of the patellar ligament for use as a graft. A six-millimeter-wide strip was obtained from the central portion of the patellar ligament with tibial and patellar bone plugs from one knee (stifle joint) of eight goats. The repair tissue that formed in the defect was characterized in terms of its structural, material, histological, and ultrastructural properties twenty-one months after the operation. The contralateral patellar ligament served as a control. Representative specimens were taken from the proximal, middle, and distal portions of the repair tissue and the control tissue for histological study and examination with transmission electron microscopy. The six-millimeter-long defect filled with repair tissue that increased the cross-sectional area by a mean of 42 per cent compared with the control values (p < 0.05). The maximum force to failure and the ultimate stress of the repair tissue were significantly decreased (by a mean of 51 and 65 per cent, respectively) compared with those of the controls (p < 0.001 for both). The stiffness also was reduced, by a mean of 27 per cent, but this was not significant (p > 0.05). Magnetic resonance imaging of the donor site showed slightly increased signal intensity compared with the intensity on the control side. Histological sections from the donor site contained collagenous (scar) tissue that was less organized, more cellular, and more vascular than the control tissue. Evaluation of the ultrastructure revealed that the repair tissue was composed primarily of collagen fibrils with a small diameter (range, fifty to 100 nanometers). CLINICAL RELEVANCE: The results of the present study suggest that the repair tissue that develops after removal of a strip of the patellar ligament for use as a graft is not comparable with normal tissue in terms of its structural, material, histological, and ultrastructural properties by twenty-one months. This should be kept in mind when this repair tissue is considered for use as a graft for revision of a reconstruction of the anterior cruciate ligament.

Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study.

BACKGROUND: Full-thickness defects measuring 3 mm in diameter have been commonly used in studies of rabbits to evaluate new procedures designed to improve the quality of articular cartilage repair. These defects initially heal spontaneously. However, little information is available on the characteristics of repair of larger defects. The objective of the present study was to define the characteristics of repair of 6-mm full-thickness osteochondral defects in the adult Spanish goat. METHODS: Full-thickness osteochondral defects measuring 6 x 6 mm were created in the medial femoral condyle of the knee joint of adult female Spanish goats. The untreated defects were allowed to heal spontaneously. The knee joints were removed, and the defects were examined at ten time-intervals, ranging from time zero (immediately after creation of the defect) to one year postoperatively. The defects were examined grossly, microradiographically, histologically, and with magnetic resonance imaging and computed tomography. RESULTS: The 6-mm osteochondral defects did not heal. Moreover, heretofore undescribed progressive, deleterious changes occurred in the osseous walls of the defect and the articular cartilage surrounding the defect. These changes resulted in a progressive increase in the size of the defect, the formation of a large cavitary lesion, and the collapse of both the surrounding subchondral bone and the articular cartilage into the periphery of the defect. Resorption of the osseous walls of the defect was first noted by one week, and it was associated with extensive osteoclastic activity in the trabecular bone of the walls of the defect. Flattening and deformation of the articular cartilage at the edges of the defect was also observed at this time. By twelve weeks, bone resorption had transformed the surgically created defect into a larger cavitary lesion, and the articular cartilage and subchondral bone surrounding the defect had collapsed into the periphery of the defect. By twenty-six weeks, bone resorption had ceased and the osseous walls of the lesion had become sclerotic. The cavitary lesion did not become filled in with fibrocartilage. Instead, a cystic lesion was found in the center of most of the cavitary lesions. Only a thin layer of fibrocartilage was present on the sclerotic osseous walls of the defect. Specimens examined at one year postoperatively showed similar characteristics. CONCLUSIONS: Full-thickness osteochondral defects, measuring 6 mm in both diameter and depth, that are created in the medial femoral condyle of the knee joint of adult Spanish goats do not heal spontaneously. Instead, they undergo progressive changes resulting in resorption of the osseous walls of the defect, the formation of a large cavitary lesion, and the collapse of the surrounding articular cartilage and subchondral bone. CLINICAL RELEVANCE: As surgeons apply new reparative procedures to larger areas of full-thickness articular cartilage loss, we believe that it is important to consider the potential deleterious effects of a "zone of influence" secondary to the creation of a large defect in the subchondral bone. When biologic and synthetic matrices with or without cells or bioactive factors are placed into surgically created osseous defects, the osseous walls serve as shoulders to protect and stabilize the preliminary repair process. It is important to protect the repair process until biologic incorporation occurs and the chondrogenic switch turns the cells on to synthesize an articular-cartilage-like matrix. It takes a varying period of time to fill a large, surgically created bone defect underlying a chondral surface. The repair of such a defect requires bone synthesis and the reestablishment of a subchondral plate with a tidemark transition to the new overlying articular surface. The prevention of secondary changes in the surrounding bone and articular cartilage and the durability of the new reparative tissue making up the articulating surface are issues that must be addressed in future studies.

Subacromial bursography. An anatomical and clinical study.

Impingement of the rotator cuff beneath the coracoacromial arch without associated rupture of the cuff or reactive bone changes on the undersurface of the acromion is a well established clinical diagnosis. The value of subacromial bursography in the assessment of this condition was investigated in an anatomical study of fifteen cadavera and a clinical study of thirty-one patients. The subacromial bursa is situated like a cap over the rotator cuff and can be demonstrated roentgenographically by the injection of contrast material in shoulders from cadavera and living subjects. This bursa is composed of subacromial and subdeltoid portions as well as a subcoracoid extension in some individuals. However, it is the anterior portion of the bursa, under the coracoacromial arch, that is most significant, since this overlies the deep structures involved in the impingement syndrome. The normal subacromial bursa easily accepts five to ten milliliters of contrast medium. However, if the bursal walls are thickened and edematous, the bursa will be difficult to demonstrate roentgenographically or it will accept only a few milliliters of contrast material. The findings in this study suggest that when the findings on the bursogram are normal, a diagnosis of chronic impingement by the coracoacromial arch should be questioned.

Survival of cells after intra-articular transplantation of fresh allografts of the patellar and anterior cruciate ligaments. DNA-probe analysis in a goat model.

The fate of donor cells in fresh allografts of the patellar and anterior cruciate ligaments was assessed after transplantation of the allografts as substitutes for the anterior cruciate ligament in goats. DNA-probe analysis was used to distinguish between the DNA of individual goats. Donor DNA was completely replaced by recipient DNA in both the transplanted patellar and anterior cruciate ligaments within a four-week period. Simultaneous full-thickness skin transplants in the same animals were not rejected during the interval of rapid loss of donor DNA from the allografts. The absence of rejection of the skin grafts at the one-week interval suggests that no pre-existing antibody associated with an immune reaction was responsible for the rapid loss of DNA in the allografts.

The effects of in situ freezing on the anterior cruciate ligament. An experimental study in goats.

We developed an in situ freeze-thaw model designed to simulate an ideally placed and oriented autogenous graft of the anterior cruciate ligament. In this model, the anterior cruciate ligament was exposed, and the femoral insertion, tibial insertion, and body of the anterior cruciate ligament were frozen in situ with specially designed freezing probes. Freeze-thaw cycles were repeated five times. We used the technique in thirty-three mature goats to study the biological and biomechanical outcomes of the devitalized and devascularized anterior cruciate ligament at zero, six, and twenty-six weeks after treatment. Thus, the collagen fibers of the simulated autogenous graft remain in normal anatomical position and the simulated graft is fixed under physiological tension. At twenty-six weeks, no statistically significant differences were noted between treated and contralateral control (untreated) ligaments relative to anterior-posterior translation, maximum force to rupture, stiffness in the linear region of the force-length curve, modulus of elasticity in the linear region, strain to maximum stress, or maximum stress. The only statistically significant difference was an increase in cross-sectional area of the ligament. This increase was 22 and 42 per cent greater than that in the control ligaments at six weeks and six months. At six months, the ligaments in the control group had an average mid-cross-sectional area of 17.7 +/- 1.2 square millimeters and the ligaments in the experimental group, 25.2 +/- 3.1 square millimeters. Changes in the size and density of the collagen fibrils also were demonstrated at six months. These observations are in sharp contrast to our previous studies of replacement of the anterior cruciate ligament, in which an allograft of the ligament or an allograft supplemented with a 3M ligament augmentation device (LAD; 3M, St. Paul, Minnesota) was used. In those studies, an average reduction in maximum strength of 75 per cent for the allografts and 50 per cent for the allografts that had a ligament-augmentation device was found at one year. We concluded that devitalized, devascularized anterior cruciate ligaments do not lose strength if the anatomical position and the orientation of the collagen fibers are not altered.

Chronic rotator cuff impingement in the throwing athlete.

Compromise of the space between the humeral head and the coracoacromial arch may be a source of chronic shoulder pain associated with rotator cuff impingement in the athlete participating in throwing sports. In certain carefully selected individuals, surgical decompression may alleviate these symptoms. The surgical procedure can be done under local anesthesia and may enable the athlete to return to his previous level of performance without disability.

Stress fracture of the ribs in female rowers.

Stress fractures of the lower ribs related to sports are rare. Fractures of the ribs related to rowing sports have not been reported. We have documented seven cases of stress fractures of the lower ribs in female athletes; four were elite rowers and three were engaged in tennis, golf, and gymnastics. Each athlete was initially seen and treated elsewhere for muscular strain. All athletes presented with pain in the posterolateral thorax in and around the scapula. The time from onset of symptoms to diagnosis ranged from 2 to 6 months. Bone scans were used to document the fractures when roentgenograms were equivocal. Each athlete responded to a 4 to 8 week period of rest or training modification. Biomechanical analysis of the forces across the ribs demonstrates that these fractures tend to occur along the posterolateral segment where the bending stresses on the rib are greatest. The predominant muscle forces are generated by the forced couple of scapular retraction and protraction acting through the serratus anterior. We postulate that inadequate strength and resistance training background in women is the cause for the apparent increased susceptibility of women to these skeletal injuries.

Cell survival after transplantation of fresh meniscal allografts. DNA probe analysis in a goat model.

UNLABELLED: Fibrochondrocytes synthesize and maintain the extracellular matrix responsible for the distinctive material and structural properties of a normal meniscus. Viable meniscal cells are believed to be necessary for the long-term maintenance of these properties in meniscal allografts. The purpose of this study was to determine if the donor cells (fibrochondrocytes) survive after a fresh meniscal allograft transplantation. A DNA probe technique was used to clearly distinguish the DNA patterns in donor cells from the host cells in the Spanish goat. No remaining donor DNA could be demonstrated at 4 weeks in transplanted meniscal tissue; it was all of host origin. The host DNA content at 4 weeks approached or exceeded the amount present in the contralateral control meniscus. CLINICAL SIGNIFICANCE: The results of this study demonstrate that viable cells in medial meniscal allografts transplanted from one animal to another do not survive. Host cells rapidly repopulate the transplanted meniscus. There is no evidence these new cells will maintain on a long-term basis the extracellular matrix of the meniscus. The evidence in this paper, that the fibrochondrocytes do not survive transplantation, suggests further justification is necessary for using grafts with living cells. Allografts with living cells have an increased expense, more complicated surgical logistics, and have a higher potential risk of disease transmission.

Epidural cortisone injections in the young athletic adult.

The lumbar epidural cortisone injection can be a useful adjunct in the conservative management of the athlete with a symptomatic lumbar disc and associated irritated neural elements. Thirty-two young athletes (ages ranging from 17 to 30 years) with a clinical diagnosis of a symptomatic lumbar disc and sciatica were treated with lumbar epidural cortisone injections. All had had disabling symptoms persisting for a minimum of 2 weeks, with an average duration of 3.6 months. Dramatic abatement of symptoms and a significantly hastened return to competiton (a positive response) was seen in 14 (44%) of the 32 athletes following injection. Although the results were encouraging, we found the success rate of this study group to be less dramatic than larger reported series in the general population.