Early identification of patients at risk for impaired tendon healing and corresponding novel therapeutic approaches are urgent medical needs. This study aimed to clarify the role of CD3+ T-cells during acute Achilles tendon (AT) healing. Blood and hematoma aspirate were taken from 26 patients during AT reconstruction, and additional blood samples were obtained during clinical follow-up at 6, 26 and 52 weeks after surgery. T-cell subsets were analyzed by flow cytometry using CD3, CD4, CD8, CD11a, CD57 and CD28 antibodies. Clinical follow-up included functional tests, MRI assessments, and subjective questionnaires. In vitro, the functional behavior of patient-derived tenocytes was investigated in co-cultures with autologous unpolarized CD4+ or CD8+ T-cells, or IFNy-polarized CD8+ or IL17-polarized CD4+ Tcells (n=5-6). This included alterations in gene expression (qPCR), MMP secretion (ELISA), migration rate (scratch wound healing assay) or contractility (collagen gels). Analysis revealed that elevated CD4+ T-cell levels and reduced CD8+ T-cell levels (increased CD4/CD8 ratio) in hematoma aspirate and pre-operative blood were associated with inferior clinical outcomes regarding pain and function at 26 and 52 weeks. Increased levels of CD8+ -memory T-cell subpopulations in blood 6 weeks after surgery were associated with less tendon elongation. In vitro, tenocytes showed increased MMP1/2/3 levels and collagen III/I ratio in co-culture with unpolarized and/or IL17-polarized CD4+ T-cells compared to unpolarized CD8+ T-cells. This coincided with increased IL17 receptor expression in tenocytes co-cultured with CD4+ T-cells. Exposure of tenocytes to IL17-polarized CD4+ T-cells decreased their migration rate and increased their matrix contractility, especially compared to IFNy-polarized CD8+ T-cells. The CD4+ /CD8+ T-cell ratio could serve as prognostic marker for early identification of patients with impaired AT healing potential. Local reduction of CD4+ T-cell levels or their IL17 secretion represent a potential therapeutic approach to improve AT healing and to prevent weakening of the tendon ECM

Introduction. In daily clinical practice, progression of spinal fusion is typically monitored during clinical follow-up using conventional radiography and Computed Tomography scans. However, recent research has demonstrated the potential of implant load monitoring to assess posterolateral spinal fusion in an in-vivo sheep model. The question arises to whether such a strain sensing system could be used to monitor bone fusion following lumbar interbody fusion surgery, where the intervertebral space is supported by a cage. Therefore, the aim of this study was to test human cadaveric lumbar spines in two states: after a transforaminal lumbar interbody fusion (TLIF) procedure combined with a pedicle-screw-rod-construct (PSR) and subsequently after simulating bone fusion. The study hypothesized that the load on the posterior instrumentation decreases as the segment stiffens due to simulated fusion. Method. A TLIF procedure with PSR was performed on eight human cadaveric spines at level L4-L5. Strain sensors were attached bilaterally to the rods to derive implant load changes during unconstrained flexion-extension (FE), lateral bending (LB) and axial rotation (AR) loads up to ±7.5Nm. The specimens were retested after simulating bone fusion between vertebrae L4-L5. In addition, the range of motion (ROM) was measured during each loading mode. Result. The ROM decreased in the simulated bone fusion state in all loading directions (p≤0.002). In both states, the measured strain on the posterior instrumentation was highest during LB motion. Furthermore, the sensors detected a significant decrease in the load induced rod strain (p≤0.002) between TLIF+PSR and simulated bone fusion state in LB. Conclusion. Implant load measured via rod strain sensors can be used to monitor the progression of fusion after a TLIF procedure when measured during LB of the lumbar spine. However, further research is needed to investigate the influence of daily loading scenarios expected in-vivo on the overall change in implant load

Abstract. Objectives. Meniscus allograft and synthetic meniscus scaffold (Actifit. ®. ) transplantation have shown promising outcomes for symptoms relief in patients with meniscus deficient knees. Untreated chondral defects can place excessive load onto meniscus transplants and cause early graft failure. We hypothesised that combined ACI and allograft or synthetic meniscus replacement might provide a solution for meniscus deficient individuals with co-existing lesions in cartilage and meniscus. Methods. We retrospectively collected data from 17 patients (16M, 1F, aged 40±9.26) who had ACI and meniscus allograft transplant (MAT), 8 patients (7M, 1F, aged 42±11) who underwent ACI and Actifit. ®. meniscus scaffold replacement. Other baseline data included BMI, pre-operative procedures and cellular transplant data. Patients were assessed by pre-operative, one-year and last follow-up Lysholm score, one-year repair site biopsy, MRI evaluations. Results. In the MAT group, the final post-operative evaluation was 7±4.5 years. The mean pre-operative Lysholm score was 49±17, rose to 66.6±16.4 1 year post-op and dropped to 58±26 at final evaluation. Four of the 17 patients had total knee replacements (TKRs) at average 6.4 years after treatment. In the Actifit. ®. group, the final post-operative assessment was 5.6±2.7years. The pre-operative Lysholm score was 53.7±21.3, increasing to 72.8±15.2 at 1 year and 70.4±27.6 at final clinical follow-up. None of the patients in the Actifit® group had received TKRs. Conclusions. Both MAT and Actifit. ®. groups were effective in improving patients symptoms and knee function according to one-year post-operative assessments. However, the knee function of patients in MAT group dropped at final follow-up, whereas the Actifit® group maintained their knee function. These preliminary findings warrant further investigations, to include more patients and alongside comparisons to ACI alone and allograft/Actifit. ®. alone as comparator groups before accurate conclusions may be drawn on the comparative efficacy of each technique. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

An increase in metal ion levels is seen after implantation of all MoM hip prosthesis due to release from the surface directly, more so during articulation and corrosion of the bearing surfaces. The bearing surfaces in MoM prosthesis consist of cobalt, chromium and molybdenum. Several case-reports of cobalt toxicity due to a MoM prosthesis have been published in the last decade. Cobalt intoxication may lead to a variety of symptoms: neuro-ocular toxicity (tinnitus, vertigo, deafness, blindness, convulsions, headaches and peripheral neuropathy), cardiotoxicity and thyroid toxicity. Nausea, anorexia and unexplained weight loss have been described. Systemic effects from metal ions even with well functioning implants or with ion concentrations lower than those associated with known adverse effects may exist and warrant investigation. The aim of this study is to investigate self-reported systemic complaints in association with cobalt ion concentrations in patients with any type of MoM hip prosthesis. A cohort study was conducted. Patients with both unilateral and bilateral, resurfacing and large head metal on metal total hip arthroplasties were included for the current study. Blood metal ion concentrations (cobalt and chromium) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Based on the known cobalt toxicity symptoms of case-reports and toxicology reports a new non-validated questionnaire was developed. questions were subdivided in general questions/symptoms, vestibular symptoms, neurological symptoms, emotional health and cardio- and thyroid toxicity symptoms. Independent samples T test, Fishers Exact Test and Pearsons (R) correlation were used. Analysis was performed on two groups; a low cobalt ion concentration group and a high cobalt ion concentration group A total of 62 patients, 36 (58%) men and 26 (42%) women, were included with a mean age at surgery of 60.8 ± 9.3 years (41.6 – 78.1) and a mean follow up of 6.3 ± 1.4years (3.7 – 9.6). In these patients a total of 71 prosthesis were implanted: 53 unilateral and 9 bilateral. Of these, 44 were resurfacing and 27 large head metal on metal (LHMoM) total hip arthroplasties. Mean cobalt and chromium ion concentrations were 104 ± 141 nmol/L (9 – 833) and 95 ± 130nmol/L (6 – 592), respectively. Based on the different thresholds (120 – 170 or 220 nmol/L) the low cobalt ion concentration group consisted of 44 (71%), 51 (82%) or 55 (89%) subjects respectively. No differences were found in general characteristics, independently of the threshold. The composite score of vestibular symptoms (vision, hearing, tinnitus, dizziness) was significantly higher (p < .050) in all high cobalt ion concentrations groups, independent of the threshold value This study aimed to detect a trend in self-reported systemic complaints in patients with metal-on-metal hip arthroplasty due to raised cobalt ion concentrations. Vestibular symptoms were more common in high cobalt ion concentration groups independent of the three threshold levels tested. The upper limit of acceptable cobalt ion concentrations remains uncertain. With regards to proactively inquired, self-reported symptoms the threshold where effects may be present could be lower than values currently applied in clinical follow-up. It is unknown what exposure to elevated metal ion concentrations for a longer period of time causes with aging subjects. Further research with a larger cohort and a more standardized questionnaire is necessary to detect previously undiscovered or under-reported effects

Background. When reversing the hard-soft articulation in inverse shoulder replacement, i.e. hard inlay and soft glenosphere, the tribological behaviour of such a pairing has to be tested thoroughly. Therefore, two hard materials for the inlay, CoCr alloy and alumina toughened zirconia ceramic (ATZ) articulating on two soft materials, conventional UHMWPE and vitamin E stabilised, highly cross-linked PE (E-XLPE) were tested. Methods. The simulator tests were performed analogue to standardised gravimetric wear tests for hip prosthesis (ISO 14242-1) with load and motion curves adapted to the shoulder. The test parameters differing from the standard were the maximum force (1.0 kN) and the range of motion. A servo-hydraulic six station joint simulator (EndoLab, Rosenheim) was used to run the tests up to 5 times 106 cycles with diluted calf serum at 37° C as lubricant. Results. The wear rates measured in the simulator when the CoCr alloy inlay articulated on UHMWPE and E-XLPE were respectively 32.50 +/− 3.48 mg/Mcycle and 10.65 +/− 2.36 mg/Mcycle. In comparison, when the ATZ inlay articulated on UHMWPE and E-XLPE the wear rates were 20.34 +/− 1.14 mg/Mcycle and 5.99 +/− 0.79 mg/Mcycle respectively. Conclusions. The simulator wear rate of the standard articulation CoCr – UHMWPE is similar to that found in the corresponding pairing for hip endoprosthesis. Replacing UHMWPE by E-XLPE, the wear rate is reduced to about 1/3 for both hard counterparts, CoCr and ZTA, respectively. Replacing the CoCr inlay by a part made from ZTA lowers wear by about 37 % in articulation against UHMWPE and about 44 % against E-XLPE. The lowest wear rate, with a reduction of about 80 % compared to the standard CoCr – UHMWPE, exhibits the pairing of both advanced materials, ZTA – E-XLPE. However, long-term clinical follow-up will confirm if this in-vitro wear reduction leads to longer in-vivo survival. Level of evidence. Laboratory test on sample implants. Study financed by Mathys Orthopaedie GmbH

Increased failure rates due to metallic wear particle-associated adverse local tissue reactions (ALTR) is a significant clinical problem in resurfacing and total hip arthroplasty. Histological analysis and particle characterization are important elements for understanding the biological mechanisms of the reaction and different histological subtypes may have unique needs for longitudinal clinical follow-up and complication rates after revision arthroplasty. Consecutive patients (N=285 cases) presenting with ALTR from three major hip implant classes, metal-on-metal resurfacing and total hip arthroplasty (THA) and non-metal-on-metal THA with dual modular neck were identified from our prospective Osteolysis Tissue Database and Repository and 53 cases were selected for wear particle nano-analysis. Conventional histology: Tissue samples taken from multiple regions around the hip with extensive sampling performed at macroscopic examination were examined by light microscopy. Particle analysis: Tissue samples selected after frozen section evaluation for cellularity and particle content were examined by scanning electron microscopy (SEM), backscatter scanning electron microscopy (BSEM), BSEM-energy-dispersive X-ray spectroscopy (EDS) element mapping examination, transmission electron microscopy (TEM), TEM-EDS element mapping, and X-ray diffraction spectrometry (XRD) examination. ALTR encompasses three main histological patterns: 1) macrophage predominant, 2) mixed lymphocytic and macrophagic, and 3) predominant sarcoid-like granulomas. Duration of implantation and composition of periprosthetic cellular infiltrates was significantly different among the three implant types examined. Distinct differences in the size, shape, and element composition of the metallic particulate material were detected in each implant class, with correlation of the severity of the adverse reaction with element complexity of the particles. ALTR encompasses a diverse range of histological patterns, which are reflective of both the implant configuration independent of manufacturer and clinical features such as duration of implantation. Distinct differences in the metallic particulate material can contribute to explain the histological features of the ALTR and variability of performance of the implants. ALTR exhibits different histological patterns and is dependent on the characteristics of the wear particulate material of each implant class and host immunological reaction

Background. Skeletal stem cells can be combined with human allograft, and impacted to produce a mechanically stable living bone composite. This strategy has been used for the treatment of femoral head avascular necrosis, and has been translated to four patients, of which three remain asymptomatic at up to three year follow-up. In one patient collapse occurred in both hips due to widely distributed and advanced AVN disease, necessitating bilateral hip arthroplasty. However this has provided the opportunity to retrieve the femoral heads and analyse human tissue engineered bone. Aims. Analysis of retrieved human tissue-engineered bone in conjunction with clinical follow-up of this translational case series. Methods. A parallel in vitro culture of the implanted cell-graft constructs was set up at the time of surgery, with serial cell viability stains performed up to six weeks. Patient follow-up was by serial clinical and radiological examination. Tissue engineered bone from the two retrieved femoral heads was analysed histologically by Alcian blue & Sirius red stain and bi-refringence, by micro computed tomography (microCT) for both bone density and morphology, and by compression testing for mechanical strength. Normal trabecular and cortical bone from the femoral heads was used as controls. Results. Parallel in vitro analysis demonstrated sustained cell growth and viability on the allograft. Histologically, the retrieved tissue engineered specimens demonstrated a mature trabecular micro-architecture and organization identical to normal trabecular bone. MicroCT revealed trabecular morphology within the tissue-engineered bone, with bone density of 1400 Grey scale units (compared to 1200 for natural trabecular bone and 1800 for cortical bone). Axial compression testing showed no difference in strength between engineered and trabecular bone. Conclusions. Widespread residual necrosis in the femoral heads of one patient resulted in collapse requiring hip arthroplasty, but analysis of the tissue engineered bone sections has demonstrated the translational potential of a living bone composite to restore both the biological and mechanical characteristics of bone defects. Clinical follow-up shows this to be an effective new treatment for focal early stage avascular necrosis of the femoral head, and this unique retrieval analysis data confirms the potential of cell-based strategies for clinical treatment of bone defects

Background. Implant stability and is an important factor for adequate bone remodelling and both are crucial in the long-term clinical survival of total hip arthroplasty (THA). Assessment of early bone remodelling on X-rays during the first 2 years post-operatively is mandatory when stepwise introduction of a new implant is performed. Regardless of fixation type (cemented or cementless), early acetabular component migration is usually the weakest link in THA, eventually leading to loosening. Over the past years, a shift towards uncemented cup designs has occurred. Besides the established hydroxyapatite (HA) coated uncemented cups which provide ongrowth of bone, new uncemented implant designs stimulating ingrowth of bone have increased in popularity. These cups initiate ingrowth of bone into the implant by their open metallic structure with peripheral pores, to obtain a mechanical interlock with the surrounding bone, thereby stabilising the prosthesis in an early stage after implantation. This retrospective study assessed bone remodelling, osseointegration and occurrence of radiolucency around a new ingrowth philosophy acetabular implant. Methods. In a retrospectively, single centre cohort study all patients whom underwent primary THA with a Tritanium acetabular component in 2011 were included. Bone remodelling, osseointegration and occurrence of radiolucency were determined by two reviewers from X-ray images that were made at 6 weeks, 3–6-12 and 24 months post-operatively. Bone contact % was calculated based on the original Charnley and DeLee zones. According to Charnley and DeLee the outer surface of an acetabular cup is divided into 3 zones (1-2-3). For our analysis the original 3 zones were further divided into 2 producing 6 zones 1A to 3B. Each of these 6 zones were then further divided into 4 equal sections. We attributed 25 points per section in which complete bone contact without lucency was observed. If lucency was observed no points were attributed to the section. A fully osteointegrated cup in all 24 sections could therefore attain 600 points. The total of each section and zone was subsequently tallied and recalculated to produce the percentage of bone contact on a 1–100% score. Results. In 2011 131 patients; 54 male and 76 female with average age of 60.83 (SD 12.42) and 60.57 (SD 12.11) year respectively underwent primary THA at our institution and all where included in our study cohort. Majority of this cohort underwent primary THA due to osteoarthrosis and most patients were classified ASO I (18%) or ASA II (65%). At two year clinical follow-up two revision were performed. One constituted a femur and acetabulum revision due to leg length difference and a snapping hip phenomenon. Complications included 3 dislocations (all treated policlinic), 4 deep infections (all treated with Genta PMMA beads with prosthesis in situ and healed) and 1 removal of hematoma. In another patient the femoral component was revised due to a peri-prosthetic fracture. Mean bone contact % values for all Charnley and DeLee zones combined were calculated and improved from 68,18% (SD 22,36) at 6 weeks to 73,61% SD (16,26) at 3 months to 84,21% (SD 19,02) at 6 months to 86,90% (SD 16,0) at 1 year to 92,19% (SD 12,74) at two year follow-up. When analysing the bone contact % per individual zone a remarkable difference was found for zones 2A-B. In contrast to zone 1A-B and 3A-B the initial bone contact % was clearly although not significantly lower until two year follow-up. Conclusions. In this study, the bone apposition around Tritanium actebular component was retrospectively assessed until two year clinical. Our results show excellent bone apposition that continues to improve over time (at least until two year clinical follow-up) suggesting that the open trabecular Ti structure of the Tritanium has a positive effect on cup osseointegration. However, some recent reports have shown the development of reactive lines around cups with porous/trabecular metal surfaces, of which the meaning is still unclear. Our analysis indicated that especially acetabular zone 2A-B according to Charnley&DeLee needs time to establish a direct contact of the implant surface and the surrounding bone tissues. Perhaps this might be explained by reaming technique (underreaming vs line to line reaming) resulting in suboptimal seating of the cup. Therefore, careful follow-up of this new implant technology will remain necessary and continued in this study. We aim to improve cohort size and establish results at longer follow-up times. Furthermore we aim to correlate these results to RSA component migration analysis

Summary. The EOS stereography system has been developed for the evaluation of prosthetic alignment. This new low-dose device provides reliable 2D/3D measurements of knee prosthesis alignment. Introduction. Achieving optimal prosthetic alignment during Total Knee Arthroplasty (TKA) is an essential part of the surgical procedure since malpositioning can lead to early loosening of the prosthesis and eventually revision surgery. Conventional weight-bearing radiographs are part of the usual clinical follow-up after both primary TKA and revision TKA (rTKA), to assess alignment in the coronal and sagittal planes. However, proportions and angles may not be correct on radiographs since divergence exists in the vertical and horizontal planes. Furthermore estimating the exact planes by looking at the position of the patella depends on rotation in the hip joint and this may be misinterpreted by the investigator. A computed tomography (CT) scanogram can also be used. However, due to high levels of radiation and costs it is not routinely used. To this end, a new device, the EOS stereography system, has been developed. With this biplanar low-dose X-ray technique, orthogonally made 2D images and 3D reconstructions can be obtained. Advantages of EOS are that images of the leg are obtained on a 1:1 scale with an amount of radiation 800–1000 times lower than CT-scans and 10 times lower than conventional radiographs. Another advantage is that the 3D reconstructions lead to determination of the real coronal and sagittal planes. However, the software for creating 3D reconstructions is developed for the lower limbs without knee prosthesis material. Consequently a reliability study concerning the generation of 2D images and 3D reconstructions of a leg containing a knee prosthesis has not been performed yet. Therefore objective of this study was to investigate interobserver and intraobserver reliability of knee prosthetic alignment measurements after rTKA using EOS. Patients and Methods. Forty anteroposterior and lateral images of 37 rTKA patients were included. Two observers independently performed measurements on these images twice. Measured angles were varus/valgus angle in 2D (VV2D) and 3D (VV3D). Intraclass correlation coefficients (ICCs) were used to determine relative reliability and the Bland and Altman method was used to determine absolute reliability. T-tests were used to test potential differences between the two observers, first and second measurement sessions and 2D and 3D measurements. Results. Relative interobserver reliability was excellent for both VV2D and VV3D with ICCs > 0.95, and no significant differences between the two observers. For the absolute reliability of VV2D, a bias of −0.16° (95%CI: −0.31–0.01) existed between both observers. Absolute reliability of VV3D was good. Relative intraobserver reliability was excellent for both VV2D and VV3D with ICCs > 0.97. No significant difference and no bias between the first and second measurements were found. A significant difference existed between the angles measured in 2D and 3D (p=0.01). Discussion / Conclusion. The EOS low-dose stereography system provides reliable varus/valgus measurements in 2D and 3D for the alignment of the knee joint with a knee prosthesis. However, significant differences exist between the varus/valgus measurements in 2D and in 3D. Therefore, a validation study is suggested to investigate the difference between the 2D measurements and 3D reconstructions and to find a possible explanation for this difference

Lumbar Spinal Canal Stenosis is a common condition in the ageing population. In Spinal decompression surgery a balance needs to be struck between the need to decompress the neural elements in the spinal canal and the risk of worsening the segmental instability that often coexists in this condition. Traditionally decompression has been supplemented with rigid stabilization e.g. fusion, which is irreversible. Recently semi-rigid or ‘soft’ stabilization philosophies have evolved. The Wallis Device is a second generation interspinous distraction/stabilization implant designed to achieve ‘soft’ segmental stabilization. In addition to stabilising the decompressed segment, it also provides a ‘block’ to full segmental extension, helping to maintain spinal canal dimensions even in the erect position. We followed up and assessed outcomes in 50 patients (25 spinal decompression + Wallis implant and 25 spinal decompression alone). The two arms of the study were matched for gender, age and level of lumbar decompression. A single surgeon was involved in each case and carried out a standard procedure of fenestration and medial facetectomy. Outcomes were assessed during clinical follow-up as well as by telephone, and included the VAS, the Oswestry Disability Index (ODI) and the EQ5D Health Domain. Early results suggest decreased incidence of recurrent symptoms and global improvement in all parameters measured, in those subjects that underwent Spinal decompression with Wallis stabilisation

Objectives

The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics.

Objectives

Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing.

Objectives

To define Patient Acceptable Symptom State (PASS) thresholds for the Oxford hip score (OHS) and Oxford knee score (OKS) at mid-term follow-up.

The cortical strains on the femoral neck and proximal femur were measured before and after implantation of a resurfacing femoral component in 13 femurs from human cadavers. These were loaded into a hip simulator for single-leg stance and stair-climbing. After resurfacing, the mean tensile strain increased by 15% (95% confidence interval (CI) 6 to 24, p = 0.003) on the lateral femoral neck and the mean compressive strain increased by 11% (95% CI 5 to 17, p = 0.002) on the medial femoral neck during stimulation of single-leg stance. On the proximal femur the deformation pattern remained similar to that of the unoperated femurs.

The small increase of strains in the neck area alone would probably not be sufficient to cause fracture of the neck However, with patient-related and surgical factors these strain changes may contribute to the risk of early periprosthetic fracture.

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.

Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months.

The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm³ (sd 261) and 545 cells/mm³ (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm³ (sd 343)) still remained lower than that of group I (1071 cells/mm³ (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

A retrospective series of 45 cases of chronic osteomyelitis collected over a period of 14 years was histologically classified into tuberculous osteomyelitis (25) and chronic non-granulomatous osteomyelitis (20). The tuberculous osteomyelitis group was divided into three subgroups: a) typical granulomas (13 cases); b) ill-defined granulomas (seven cases), and c) suspected granulomas (five cases). An in-house polymerase chain reaction amplifying the 245 bp nucleotide sequence, and capable of detecting 10 fg of DNA of Mycobacterium tuberculosis, was used on the DNA extracted from the paraffin blocks. The polymerase chain reaction was positive in 72% of cases (18) of tuberculous osteomyelitis, but when typical cases of tuberculous osteomyelitis with confirmed granulomas were considered (13), this increased to 84.6% (11). The chronic non-granulomatous osteomyelitis group gave positive polymerase chain reaction results in 20% of the cases (4).

Our preliminary study on tuberculous osteomyelitis shows that the polymerase chain reaction can be a very useful diagnostic tool, since a good correlation was seen between typical granulomas and polymerase chain reaction with a sensitivity of 84.6% and a specificity of 80%. In addition, our study shows that tuberculous osteomyelitis can be diagnosed in formalin-fixed paraffin-embedded tissues in the absence of typical granulomas.