Autoimmunity in Acute Poststreptococcal GN: A Neglected Aspect of the Disease

Acute poststreptococcal GN (APSGN) is the prototype of immune complex GN and is associated with manifestations of autoimmune reactivity that have been neglected as epiphenomena. Recently, studies have demonstrated transient antifactor B autoantibodies that activate the alternative complement pathway, bringing self-immunity to a central position in the pathogenesis of APSGN. Therefore, examining other manifestations of autoimmunity that have been reported in association with poststreptococcal GN is of interest. This article reviews the renal and extrarenal manifestations of autoimmune reactivity in APSGN and considers their potential relevance in modifying the usually benign clinical course of the disease. It also discusses related aspects of the nephritogenic antigens, complement activation, and genetic elements associated with immune reactivity and their potential relevance to the familial incidence of the disease.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Sites of [3H]taurine Uptake in the Rat Substantia Nigra in Relation to the Release of Taurine from the Striatonigral Pathway

The autoradiographic localization of radiolabelled taurine taken up in the rat substantia nigra in vivo together with conditions of release of the [3H]taurine taken up into brain slices were studied to determine whether they are consistent with the hypothesis that taurine may act as a neurotransmitter in the striatonigral pathway. At the light microscopic level the main cellular elements that became radiolabelled following the injection of [3H]taurine into the substantia nigra could be identified as glial cells. Electron microscope autoradiography confirmed that a subpopulation of glial cells including astrocytes, pericytes, and oligodendrocytes were radiolabelled and that neuronal perikarya were not radiolabelled. In addition, axonal elements including both terminal and preterminal boutons were found to have silver grains overlying them and were thus considered to be radiolabelled. This was supported by a quantitative analysis of the distribution of the silver grains; whereas glial elements had a significantly higher number of grains associated with them than with any other structure, axonal elements had a significantly greater number of grains than dendritic structures. Release of the preloaded [3H]taurine from superfused slices of substantia nigra occurred in response to veratridine, was calcium-dependent and was sensitive to inhibition by high magnesium concentrations or tetrodotoxin. Following the destruction of neurons in the striatum by ibotenic acid injections, although the weight of the ipsilateral substantia nigra was reduced, the uptake of [3H]taurine was not altered. In contrast to this, the veratridine-stimulated release was markedly attenuated, implying that the destruction of striatal neurons causes the loss of sites in the substantia nigra from which exogenous taurine is released. These results add further support to previous suggestions that taurine might act as a neurotransmitter or neuromodulator in the striatonigral pathway.     

Recovery of response to adriamycin and cyclophosphamide by lonidamine in previously treated metastatic breast-cancer patients

Thirty-one patients with metastatic breast cancer not responding or progressing after initial response to adriamycin + cyclophosphamide (AC) treatment entered a phase 11 study with oral lonidamine in association to AC. Objective clinical responses were observed in 10 patients (32%) and consisted of 1 complete + 9 partial remissions. Disease stability and progression were observed in 8 and 13 cases, respectively. These results were obtained with a marginal toxicity in addition to that already reported for AC therapy, the main additional side effect being myalgia, which was easily manageable in most cases.     

Injuries of the distal radioulnar joint

Injuries of the distal radioulnar (DRU) joint are common. If the joint is unstable or discongruous, attempts should be made to restore anatomic alignment and stability. Although most acute injuries of the DRU joint are easily treated, they are often overlooked or misdiagnosed because they usually occur in association with other major injuries of the upper limb. Acute and chronic abnormalities are described briefly and the treatment for each is discussed. Appropriate diagnosis and management of the acute injury will yield a much higher success rate than reconstructive procedures to correct a chronic disorder. A differentiation should be made between DRU joint dysfunction and ulnar impingement against the carpus; ulnar shortening is the most commonly used technique to treat the latter condition. In an elderly patient, a Darrach procedure is the preferred treatment for a DRU joint dysfunction; in younger patients, the treatment of choice appears to be resection arthroplasty of the DRU joint with preservation of the ulnar length, the ulnar styloid, and the triangular fibrocartilage complex (TFCC). In cases of malunion of the distal radius with involvement of the DRU joint, the recommended treatment is corrective osteotomy and soft tissue reconstruction of the ligamentous support of the joint.     

Prophylaxis and treatment of NSAID-induced gastroduodenal disorders.

A significant percentage of patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) experience some type of adverse gastrointestinal symptoms, lesions of the gastroduodenal tract being clinically the most relevant. NSAIDs cause gastrointestinal damage by 2 independent mechanisms: a topical effect, which is pH and pKa related, and a systemic effect mediated by cyclooxygenase (COX) inhibition with a reduction in prostaglandin synthesis. Using endoscopy, gastroduodenal lesions identified include subepithelial haemorrhages, erosions and ulcers. The prevalence of ulceration in NSAID users has been reported as being between 14 and 31% with a 2-fold higher frequency of gastric ulcers compared with duodenal ulcers. Among the strategies used to decrease the risk of ulcer development are: (i) the use of analgesics other than NSAIDs; (ii) use of the lowest possible dosage of NSAID; (iii) the use of a COX-2 selective NSAID; (iv) the use of low doses of corticosteroids instead of NSAIDs; (v) avoidance of concomitant use of NSAIDs and corticosteroids; and (vi) use of preventive therapy. In an attempt to reduce the incidence of NSAID-induced gastrointestinal lesions, the following approaches have been proposed: (i) use of the prostaglandin analogue misoprostol, which is an antiulcer drug which has been proven to be as effective in the prevention of NSAID-induced gastric and duodenal ulcers as in the reduction of serious upper gastrointestinal complications; (ii) histamine H2 receptor antagonists (H2 antagonists), e.g. ranitidine, cimetidine and famotidine, which are useful in the prevention of NSAID-induced duodenal ulcers during long term treatment, but not in the prevention of NSAID-induced gastric ulcers; (iii) proton pump inhibitors, e.g omeprazole, and pantoprazole, whose efficacy in preventing NSAID-associated ulcers has been recently demonstrated; and (iv) barrier agents, e.g. sucralfate, which cannot be recommended as prophylactic agents to prevent NSAID-induced gastropathy. The first step in the treatment of NSAID-associated ulcers lies in a reduction in the dosage of the NSAID or discontinuation of the drug. If NSAID treatment cannot be withdrawn, a proton pump inhibitor appears to be the most effective treatment in healing ulcers, accelerating the slow healing observed with H2 antagonists.