A double-blind, multicentre, placebo-controlled study of tiludronate in Paget's disease of bone.

A multicentre, randomised, placebo-controlled, dose-ranging study was conducted to investigate the therapeutic activity and sustained efficacy of tiludronate (200 mg, 400 mg and 600 mg once daily) taken orally for 12 weeks in patients with Paget''s disease. Serum alkaline phosphatase concentrations were compared with baseline at weeks 12 and 24; treatment success was defined as a 50% reduction compared with baseline. Changes in the hydroxyproline: creatinine ratio were also measured. Pain was assessed using the Huskisson Visual Analogue Scale and by questionnaire. Patients completing at least 11 weeks of treatment were followed-up 18 months later by postal questionnaire. Significantly greater numbers of patients in the tiludronate groups successfully responded to treatment compared with the placebo group. A dose-response was observed; the percentage of patients responding to treatment being 31% (200 mg), 52% (400 mg) and 82% (600 mg) at week 12 and 45% (200 mg), 70% (400 mg) and 82% (600 mg) at week 24. Tiludronate treatment also significantly reduced hydroxyproline: creatinine ratios compared with placebo, again showing a dose response. Dose-related gastrointestinal symptoms were the commonest adverse events, occurring in 2.4%, 11.0%, 5.5% and 18.9% of patients receiving placebo and tiludronate 200, 400 and 600 mg daily, respectively. The response to oral tiludronate was sustained for more than 18 months in some patients and there was evidence of a reduction in the longer term complications of the disease. These results show that oral tiludronate is an effective, well-tolerated treatment for Paget''s disease; the 400 mg once daily dose appears to offer the optimum balance of efficacy and tolerance.     

A six-year follow-up study of smoking habits and microvascular complications in young adults with type 1 diabetes.

One hundred insulin-dependent diabetic patients (age < 45 years, 53 smokers) were followed for six years. The age, duration of diabetes and mean glycated haemoglobin levels, were comparable between the smokers and non-smokers. Microvascular complications (retinopathy and increased urine albumin excretion) were commoner and more severe in the smoking group at six years, particularly in heavy smokers. Of the 45 original smokers reviewed at six years, 12 (27%) had stopped, six of whom had developed microvascular complications. Only two of the ''heavy'' initial smokers, likely to be at most risk, had stopped smoking, and three original non-smokers had started smoking.     

The Doppler guide wire: clinical applications in neuroendovascular treatment

The application of Doppler-tipped guide wires to measure blood flow velocity in coronary and peripheral arteries has been described previously as a valuable means of functional assessment in interventional cardiological procedures. In animal studies intravascular Doppler has been used in the cerebrovascular system, and this appears to be an important field of application for this new technique. We used intravascular haemodynamic monitoring by the Doppler guide wire during neuroendovascular procedures in patients with different cerebrovascular diseases and evaluated the clinical feasibility of the method. We found it a safe technique which complements morphological angiographic information with valuable functional data. Further studies may be expected to demonstrate the relation of flow parameters to clinical outcome. Received: 16 January 1996 Accepted: 30 January 1996     

Magnetic susceptibility measurement of insoluble solids by NMR: Magnetic susceptibility of bone.

Measurements of the volume magnetic susceptibility of solids using the classical Gouy balance approach are hampered by variations in apparent density of the packed powder. In this paper a quantitative NMR measurement of the volume magnetic susceptibility of powdered solids is described and the volume susceptibility of bone is reported. The technique is based on the measurement of changes in incremental linewidth (1/πT₂′) induced in a marker fluid whose susceptibility can be predictably modified by changing the composition, such as by addition of a soluble diamagnetic compound. The spectroscopic linewidth of the marker fluid is determined by the susceptibility difference between the fluid and the suspended solid. Changes in the linewidth are accompanied by bulk magnetic susceptibility induced frequency shifts in the fluid resonance. Correlating the two dependencies allows measurement of the absolute volume susceptibility of the solid. The susceptibility of bovine rib bone was found to be ?0.90 ± 0.02 × ^? 10^?6 (CGS) confirming previous estimates which suggested bone to be more diamagnetic than the marrow constituents. Knowledge of the susceptibility of bone is relevant in view of the growing interest in MRI osteodensitometric techniques.     

Fractured talar beaks

The talar beak is a well-described secondary sign of talocalcaneal coalition but is not pathognomonic of the condition and may be seen in other causes of restricted or abnormal subtalar motion. We present an unusual complication of talar beaks in two patients who sustained fractures through their beaks. One of the patients described did not have a talocalcaneal coalition but had developed a beak following a compound fracture dislocation of the ankle joint complicated by infection, a previously undescribed predisposing cause.     

Donor left ventricular hypertrophy increases risk for early graft failure

A review of factors contributing to early mortality after cardiac transplantation revealed that up to 25 % of deaths were due to primary graft dysfunction unrelated to rejection or infection. In light of this finding, evaluation of a donor heart with regard to its suitability for transplantation takes on added importance. In an effort to screen the suitability of donor hearts in the region covered by the Northwest Organ Procurement Agency (USA), all donors are evaluated by two-dimensional transthoracic echocardiography as part of the initial evaluation. A total of 110 donor echocardiograms were reviewed and an attempt was made to correlate the 30-day outcome with the parameters measured. An unexpected finding was that the presence of left ventricular hypertrophy in the donor heart was associated with an increase in the incidence of donor heart dysfunction compared with donors with normal echocardiographic profiles (33 % vs 3 %, P = 0.007). Received: 12 February 1996 Received after resision: 27 June 1997 Accepted: 14 July 1997     

Homologous testis transplantation in dogs

There is growing interest in the possible use of homologous testis transplantation for the treatment of anorchia and male infertility. In order to test the surgical and immunological feasibility of this therapy, three series of experimental studies of homologous testis transplantation were carried out in dogs. In the first pilot study, four beagles from the same litter were transplanted using microsurgical techniques for end-to-end anastomosis of the testicular vessels and the vas deferens. These dogs received cyclosporin A (CyA) for 3 months after transplantation. The longest functional graft survival in this series was 163 days, strongly suggesting that long-term survival of a homologously transplanted testis graft is possible. A second series of operations was performed on ten mongrel dogs. The same surgical technique was employed and the series was divided into three groups. Group 1 received CyA monotherapy, group 2 a combination of CyA and prednisolone, and group 3 received no immunosuppression. The average graft survival time in this series was 18 days, significantly less than the 71 days in the first series. The dogs in group 2, however, had graft survival times that were three times longer than those in the other two groups, suggesting that CyA in combination with prednisolone yields the best graft survival. In the third series, five littermates received a testis graft after castration. Immunosuppression was achieved by administration of CyA and prednisolone for 3 months. In three out of five animals, the graft survived until the immunosuppressive therapy was suspended. Histological biopsies of the graft 3 months after transplantation showed the same maturation of sperm cells as in the control testis of the same dog. The results of the last series suggest that long-term survival of homologously transplanted testis grafts in dogs is, indeed, possible with the aid of CyA and prednisolone. Received: 14 August 1996 Received after revision: 21 March 1997 Accepted: 24 April 1997     

Interstitial and vascular pancreas rejection in relation to graft survival

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas grafts that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i. e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection.We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR andVR, a pancreas biopsy may provide important diagnostic as well as prognostic information. Received: 6 March 1997 Received after revision: 5 June 1997 Accepted: 30 June 1997