Sacral insufficiency fractures: an unsuspected cause of low back pain [clinical conference]

We describe 10 cases of sacral fractures diagnosed within the rheumatology department at Southend Hospital over the last 5 yr. All presented with sudden-onset low back pain. The majority were elderly, frail, with chronic inflammatory disease (six with rheumatoid arthritis, one with polymyalgia rheumatica, one with vasculitis) and had received steroids. Diagnosis was delayed by the inability of plain radiographs to show these fractures and was ultimately demonstrated by technetium scintigraphy/computed tomography scan. We feel that this diagnosis should be considered in elderly patients with rheumatoid arthritis or other risk factors for osteoporosis who present with low back pain and sacral tenderness. Further clues may be parasymphyseal tenderness (suggesting associated pubic ramus fracture), elevated alkaline phosphatase and plain radiograph showing pubic ramus fractures or parasymphyseal sclerosis. Patients with this complication generally have a poor prognosis and two of our patients have died. Seven required in-patient stay (mean 20 days; range 14-41). The mortality, morbidity and costs incurred in management may be comparable to those of femoral neck fractures.      

3H]TA-3090, a selective benzothiazepine-type calcium channel receptor antagonist: in vitro characterization

Binding of the new benzothiazepine calcium channel blocker, (+)-(2S,3S)-3-acetoxy-8-chloro-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2- (4- methoxyphenyl)-1,5-benzothiazepine-4-(5H)-one maleate, [3H]TA-3090), was characterized and its specificity for rat myocardial benzothiazepine receptors described. Scatchard plots and nonlinear regression analysis of specific [3H]TA-3090 binding best fit a one-site binding model (Kd = 8.8 +/- 2.7 nM, Bmax = 132 +/- 38 fmol/mg protein). Kinetically derived affinity constants were in close agreement (Kd = 7.86 nM) with those obtained from analysis of equilibrium binding data. In comparison, under identical conditions [3H]diltiazem exhibited a Kd of 38 nM and Bmax, 106 fmol/mg protein. Specific binding was saturable, reversible and stereoselective (d-cis-TA-3090 Ki = 14 nM; 1-cis-TA-3090 Ki = 2700 nM). Competitions for [3H]TA-3090 binding were conducted with nifedipine, propranolol, prazosin, quinuclidinyl benzilate, verapamil and yohimbine. Only the calcium channel blockers nifedipine and verapamil inhibited specific [3H]TA-3090 binding. Nifedipine could maximally inhibit only 52% of specifically bound [3H]TA-3090 at 10 microM. In contrast, however, 10 microM verapamil completely inhibited specific radioligand binding (Ki = 93 +/- 28 nM) but with six times less efficacy than TA-3090. Thus, these data demonstrate that [3H]TA-3090 is a potent radioligand selective for the benzothiazepine binding site and is consistent with the hypothesis that [3H]TA-3090 interacts with a myocardial benzothiazepine receptor site.     

Plasmapheresis in the treatment of acute renal failure in multiple myeloma.

Three patients with multiple myeloma and severe acute renal failure were treated by repeated plasmapheresis. Recovery of renal function was observed in all. The pathogenetic role of light chains and the possible mechanisms responsible for renal damage are discussed. It is suggested that the removal of light chains by plasmapheresis may be of therapeutic value in this condition.