Growth hormone deficiency after childhood bone marrow transplantation with total body irradiation: interaction with adiposity and age.

OBJECTIVE: Bone marrow transplantation with total body irradiation (BMT/TBI) has adverse effects on growth, growth hormone status and adiposity. We investigated the GH-IGF-I axis in relation to adiposity. DESIGN: Cross-sectional case control study. PATIENTS: BMT/TBI survivors (n = 22) and short stature control participants (n = 19), all GH-naïve or off GH treatment >3 months. MEASUREMENTS: Auxology, DEXA scans and GH-IGF-I axis investigation: (i) 12-h overnight GH profiles; (ii) insulin tolerance test (ITT); and (iii) IGF-I generation test. ANALYSIS: auto-deconvolution of GH profile data and comparison of quantitative parameters using ANOVA. RESULTS: Eighty-two percent of BMT/TBI survivors had growth hormone deficiency (GHD) using ITT. GH profile area-under-the-curve (GH-AUC) was reduced in BMT/TBI survivors vs short stature control participants [geometric mean (range) 209 (21-825) vs 428 (64-1400) mcg/l/12 h, respectively, P = 0·007]. GHD was more marked in those who had additional cranial irradiation (CRT) [ITT peak 1·4 (0·2-3·0) vs TBI only 4·1 (1·1-14·8) mcg/l, P = 0·036]. GHD was more marked at the end of growth in BMT/TBI survivors vs short stature control participants (GH-AUC 551 (64-2474) vs 1369 (192-4197) mcg/l/12 h, respectively, P = 0·011) and more prevalent (9/11 vs 1/9, respectively, P = 0·005). GH profile data were consistent with ITT results in 80% of participants. IGF-I generation tests were normal. BMT/TBI survivors still demonstrated lower GH levels after adjustment for adiposity (fat-adjusted mean difference for GH-AUC 90·9 mcg/l/12 h, P = 0·025). CONCLUSIONS: GHD was more prevalent in BMT/TBI survivors than expected for the CRT dose in TBI, worsened with time and persisted into adulthood. GHD could not be explained by adiposity. There was no evidence of GH neurosecretory dysfunction or resistance after BMT/TBI.

Effect of pamidronate in preventing local bone loss after total hip arthroplasty: a randomized, double-blind, controlled trial.

Acute periprosthetic bone loss occurs after total hip arthroplasty. Bone loss undermines the support of the implant and may contribute to prosthetic failure. At present, there is no established prophylaxis for this process. We studied the effect of a single-dose infusion of 90 mg of pamidronate on early periprosthetic bone mineral density (BMD), biochemical markers of bone turnover, radiological, and clinical outcome in a 26-week, prospective, randomized, double-blinded study of 47 men and women undergoing total hip arthroplasty. Pamidronate therapy led to a significant reduction in bone loss compared with placebo for both the proximal femur and the pelvis (repeated measures analysis of variance [ANOVA]); p = 0.001 and p = 0.01, respectively). Pamidronate therapy was associated with suppression of all biochemical markers of bone turnover compared with placebo (repeated measures ANOVA; p < 0.05 for all comparisons), with the exception of urinary free deoxypyridinoline. Pamidronate did not interfere with the clinical improvement in symptoms after total hip arthroplasty, or radiological outcome, and was not associated with an increase in adverse events. This study provides clinical data on the efficacy and safety of bisphosphonates for the prevention of bone loss after total hip arthroplasty and supports the establishment of larger-scale clinical trials to determine the long-term clinical efficacy of this intervention using implant failure as the primary endpoint.

Rupture of the central slip of the extensor hood of the finger. A test for early diagnosis.

Closed rupture of the middle slip of the extensor hood of a finger is easily missed until the late appearance of a buttonhole deformity. Early diagnosis gives the best chance of satisfactory treatment, but Boyes' test becomes positive only at a late stage. A new test is described in which, from a 90 degree flexed position over the edge of a table, the patient tries to extend the proximal interphalangeal joint of the involved finger against resistance. The absence of extension force at the proximal joint and fixed extension at the distal joint are immediate signs of complete rupture of the central slip. The theoretical basis and the method of performing the test are discussed.

Changes in allograft bone irradiated at different temperatures.

Secondary sterilisation of allograft bone by gamma irradiation is common, but the conditions under which it is performed vary between tissue banks. Some do so at room temperature, others while the bone is frozen. Bone is made brittle by irradiation because of the destruction of collagen alpha chains, probably mediated by free radicals generated from water molecules. Freezing reduces the mobility of water molecules and may therefore decrease the production of free radicals. We found that bone irradiated at -78 degrees C was less brittle and had less collagen damage than when irradiated at room temperature. These findings may have implications for bone-banking.

Bacterial infection and acrylic cement in the rat.

In thirty-one rat tibiae, plugs of plain acrylic cement were inoculated with Staphylococcus aureus; these all remained contaminated at the end of two weeks when the animals were killed. Inoculation with known strains of Pseudomonas, Proteus and Gp. G Streptococcus resulted in 70 to 93 per cent persisting contamination. Gentamicin, to which the organisms were fully sensitive, was efficacious in controlling the infection (90 per cent plugs proving sterile after two weeks). Fucidin was less successful against Staphylococcus aureus although effective in vitro. Intravenous inoculation with a suspension of Staphylococcus aureus succeeded in contaminanting 70 per cent of sixty plain cement plugs when injected into the tail vein half an hour after closure of the leg wounds. Only 11 per cent of sixty-four plugs were so contaminanted when the injection was delayed for two weeks. This animal model is submitted as a possible future means of testing different antibiotic-cement combinations against infection.

Deep infection of cemented total hip arthroplasties caused by coagulase-negative staphylococci.

We reviewed a series of 91 patients with deep infection of a cemented total hip arthroplasty caused by coagulase-negative staphylococci (C-NS). Of these, 72 were treated by one-stage exchange arthroplasty with a failure rate of 13% due to recurrence of infection. The other 19 patients have started or completed treatment by a two-stage exchange without failure to date. In 27 of the 91 patients multiple strains of C-NS were discovered, many being resistant to previously used antibiotics. The use of gentamicin-containing cement in the primary arthroplasty was significantly associated with the emergence of gentamicin-resistant C-NS in subsequent deep infection. Bacteriological diagnosis of such infections must take into consideration the possibility that multiple strains of the organism are involved.

Antibiotic-loaded acrylic cement.

Laboratory experiments and clinical investigations have confirmed the various claims made originally by Buchholz and Engelbrecht (1970) that antibiotic-loaded acrylic cement releases the antibiotic into the surroundings in useful concentrations. Palacos R cement released higher concentrations than CMW, Simplex and Sulfix brands of cement and over longer periods. Concentrations of gentamycin and fucidin were sufficient to penetrate dead cortical bone. These conclusions need to be assessed with animal studies, mechanical testing and clinical results before the ideal place of antibiotic-loaded acrylic cement is established.

The saddle prosthesis for salvage of the destroyed acetabulum.

We report the 12 to 74 month results of our mark I saddle prosthesis after its use as a salvage device for gross loss of pelvic bone stock in 76 patients with failed hip arthroplasties. The implant transmits load between iliac bone and bare polish chrome-cobalt. Our clinical and radiological results indicate that a useful and stable articulation can be achieved in most cases, provided that continued deep infection can be avoided. The appearance of radiological sclerosis at the bearing site in successful cases seems to indicate that significant late migration will not occur. Based on our experience with the mark I prosthesis we have designed and developed a mark II model which has freedom of axial rotation of the saddle. Our early results in 40 cases show a significant improvement over the results which could have been predicted for the mark I device.

Measuring bone mineral density of the pelvis and proximal femur after total hip arthroplasty.

We aimed to evaluate the precision and longitudinal sensitivity of measurement of bone mineral density (BMD) in the pelvis and to determine the effect of bone cement on the measurement of BMD in femoral regions of interest (ROI) after total hip arthroplasty (THA). A series of 29 patients had duplicate dual-energy x-ray absorptiometry (DXA) scans of the hip within 13 months of THA. Pelvic analyses using 3- and 4-ROI models gave a coefficient of variation (CV) of 2.5% to 3.6% and of 2.5% to 4.8%, respectively. Repeat scans in 17 subjects one year later showed a significant change in BMD in three regions using the 4-ROI model, compared with change in only one region with the 3-ROI model (p < 0.05). Manual exclusion of cement from femoral ROIs increased the net CV from 1.6% to 3.6% (p = 0.001), and decreased the measured BMD by 20% (t = 12.1, p < 0.001). Studies of two cement phantoms in vitro showed a small downward drift in bone cement BMD giving a measurement error of less than 0.03 g/cm2/year associated with inclusion of cement in femoral ROIs. Changes in pelvic periprosthetic BMD are best detected using a 4-ROI model. Analysis of femoral ROI is more precise without exclusion of cement although an awareness of its effect on the measurement of the BMD is needed.

Management of deep infection of total hip replacement.

Exchange operation is recommended as the treatment of choice for most deep infections involving a total hip replacement. This revision arthroplasty comprises, in one stage, excision of soft tissue, removal of implant and cement, replacement with an appropriate implant using Palacos R acrylic cement loaded with an appropriate antibiotic and, more recently, systemic antibiotics. During our first 10 years without systemic antibiotics we have achieved an overall 77 per cent success rate from a first attempt in 583 patients and a 90 per cent success rate after subsequent exchange procedures. Morbidity is significant but acceptable. Success is defined as control of infection, no loosening, and useful function. The factors associated with failures include, in particular, specific infections (Pseudomonas group, Streptococcus group D, Proteus group, and Escherichia coli), delay in operation and inadequate antibiotic dosage in the cement.

Biochemical properties of cortical allograft bone using a new method of bone strength measurement. A comparison of fresh, fresh-frozen and irradiated bone.

There have been conflicting reports on the effects of gamma irradiation on the material properties of cortical allograft bone. To investigate changes which result from the method of preparation, test samples must be produced with similar mechanical properties to minimise variations other than those resulting from treatment. We describe a new method for the comparative measurement of bone strength using standard bone samples. We used 233 samples from six cadavers to study the effects of irradiation at a standard dose (28 kGy) alone and combined with deep freezing. We also investigated the effects of varying the dose from 6.8 to 60 kGy (n = 132). None of the treatments had any effect on the elastic behaviour of the samples, but there was a reduction in strength to 64% of control values (p < 0.01) after irradiation with 28 kGy. There was also a dose-dependent reduction in strength and in the ability of the samples to absorb work before failure. We suggest that irradiation may cause an alteration in the bone matrix of allograft bone, but provided it is used in situations in which loading is within its elastic region, then failure should not occur.

Exchange arthroplasty for infection. Perspectives from the United Kingdom.

A number of factors are considered with a bearing on outcome assessment and survivorship analysis. The results achieved in more than 440 exchange arthroplasties are discussed. Despite the apparent threefold increased risk of recurred infection associated with a one-stage approach, this statistic is an oversimplification of the many complex factors involved in the analysis of these results and in the decision between a one- and a two-stage approach to treatment, when presented with an infected hip replacement. The authors think that a one-stage approach remains a reasonable alternative, given certain prerequisites.

Skin closure using staples and nylon sutures: a comparison of results.

A disposable skin stapler (Elite: Auto Suture UK Ltd) and Nylon vertical mattress sutures have been used for skin closure. The complications related to each method were evaluated in 129 wounds. There was a higher incidence of inflammation, discomfort on removal and spreading of the healing scar associated with staples. The only advantage of staples was speed of wound closure.

A new method of comparative bone strength measurement.

Most investigations of the material properties of bone have been concerned with the measurement of absolute values for various mechanical parameters. It can be necessary, however, to produce test samples with similar mechanical properties in order to assess the effect on these properties of particular treatments. Absolute values for these properties may not be as important as any changes observed. We describe here a new method whereby many bone test samples with very similar mechanical properties can be produced. If the femoral shaft at the diaphysis is cut in transverse section, it is possible to produce many similar shaped rings of bone. We compared the material properties of 48 ring samples with 65 beam specimens. Both were tested in three-point bending. Global estimates of coefficient of variation (CV) for each parameter were used to assess similarity within each group. All the rings had very similar ash weights (1.98%), thicknesses (1.97%), and diameters (< 0.01%). Values of load/deflection of the rings were more similar than the values of Young's modulus (E) for the beams (7.06 versus 9.9%), and the maximum loads sustainable by the rings were more similar than the bending strengths of the beams (5.7 versus 13.6%). The energy absorbed by the ring samples were more consistent than the beams (14.31 versus 34.41%). We suggest that there is improved similarity in mechanical characteristics within groups of samples produced in this manner than with more conventional sample configurations.

Measurement of hip range of flexion-extension and straight-leg raising.

We believe there is a degree of inaccuracy in the usual methods of evaluation of range at the hip in the sagittal plane, ie, flexion-extension. We describe a simple method of measuring more accurately the range of hip flexion-extension, presuming such ranges of motion should relate to the anatomic position of the pelvis. We used this technique for the measurement of flexion and extension of the left hip in a cohort of 200 healthy individuals; we found a wide range of both flexion (80 degrees-140 degrees ) and extension (5 degrees-40 degrees ). Especially with respect to extension, we believe more conventional methods underestimate the ranges of motion. As a corollary to this study, we suggest some reappraisal of the straight-leg-raising test by which pain from nerve root tension can be distinguished from a source of pain arising locally in intervertebral joints for mechanical reasons or from the hip itself. We recommend the method described as being useful in the consulting office.