Regulation of mineral metabolism by lithium

Lithium, an inhibitor of glycogen synthase kinase 3 (GSK3), is widely used for the treatment of mood disorders. Side effects of lithium include nephrogenic diabetes insipidus, leading to renal water loss. Dehydration has in turn been shown to downregulate Klotho, which is required as co-receptor for the downregulation of 1,25(OH)₂D₃ formation by fibroblast growth factor 23 (FGF23). FGF23 decreases and 1,25(OH)₂D₃ stimulates renal tubular phosphate reabsorption. The present study explored whether lithium influences renal Klotho expression, FGF23 serum levels, 1,25(OH)₂D₃ formation, and renal phosphate excretion. To this end, mice were analyzed after a 14-day period of sham treatment or of treatment with lithium (200 mg/kg/day subcutaneously). Serum antidiuretic hormone (ADH), FGF23, and 1,25(OH)₂D₃ concentrations were determined by ELISA or EIA, renal Klotho protein abundance and GSK3 phosphorylation were analyzed by Western blotting, and serum phosphate and calcium concentration by photometry. Lithium treatment significantly increased renal GSK3 phosphorylation, enhanced serum ADH and FGF23 concentrations, downregulated renal Klotho expression, stimulated renal calcium and phosphate excretion, and decreased serum 1,25(OH)₂D₃ and phosphate concentrations. In conclusion, lithium treatment upregulates FGF23 formation, an effect paralleled by substantial decrease of serum 1,25(OH)₂D₃, and phosphate concentrations and thus possibly affecting tissue calcification.     

How to diagnose and treat secondary forms of vasculitis

Vasculitis is considered to be secondary when it arises either in the context of a pre-existing connective tissue disease, as a result of direct infection with a limited range of organisms, especially viruses, or when it arises in response to exposure to a number of medications. Rheumatoid vasculitis is probably the most widely recognised form of secondary vasculitis, and in this article we review the incidence, clinical features and management of this condition. Infections may either trigger or cause some types of vasculitis. Drug therapy is a common cause of limited forms of vasculitis and may enhance our understanding of the mechanism of these diseases. The premature development of atherosclerosis in patients with existing connective tissue diseases or indeed primary vasculitis has been recognised for some time, and the underlying mechanisms are currently being studied. An appreciation of the complex and varied pathophysiology of secondary vasculitis may further our understanding of primary vasculitis.     

Haematological and clinical features of beta-thalassaemia associated with Hb Dhofar

Hb Dhofar is a variant haemoglobin (β^{29 (GGC–GGT) gly-gly}, β^{58 (CCT–CGT) pro-arg}) associated with a thalassaemic phenotype and unique to the Sultanate of Oman. We report clinical and haematological data on 54 subjects with Hb Dhofar (37 heterozygotes, 14 homozygotes and three compound heterozygotes with a different β-thalassaemia mutation). In heterozygotes, the level of Hb Dhofar ranged from 8.8% to 21.5%. All heterozygotes had Hb A₂ > 3.5%, consistent with β-thalassaemia trait. Hb Dhofar in homozygotes and compound heterozygotes ranged from 26% to 59.7%, with a peripheral film consistent with homozygous β-thalassaemia. Age at presentation in homozygotes ranged between 6 months and 8 yr, with a majority presenting before 5 yr of age. All had splenomegaly and six (43%) had undergone splenectomy. All had some degree of frontal bossing and in particular, two patients with infrequent transfusions had marked thalassaemic facies and stunting of growth. Hb Dhofar can be mistaken for Hb D as the electrophoretic mobility is similar, but differs from it by a variable and reduced quantity of variant Hb in both heterozygotes and homozygotes. Clinical and haematological data suggest that this mutation behaves like a moderately severe β⁺ thalassaemia allele resulting in a thalassaemia intermedia phenotype.     

Actinomycotic pseudo-tumour of the mid-cervical region (a case report)

Cervicofacial actinomycosis is today a rare disease in our country. Isolated actinomycotic neck masses are extremely rare. A case of young man with an isolated midcervical tumour like actinomycotic granuloma without sinuses or discharging granules is reported here.     

Anatomical glenoid reconstruction for recurrent anterior glenohumeral instability with glenoid deficiency using an autogenous tricortical iliac crest bone graft

BACKGROUND: Anterior shoulder instability associated with severe glenoid bone loss is rare, and little has been reported on this problem. Recent biomechanical and anatomical studies have suggested guidelines for bony reconstruction of the glenoid. HYPOTHESIS: Anatomical glenoid reconstruction will restore stability in shoulders with recurrent anterior instability owing to glenoid bone loss. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Eleven cases of traumatic recurrent anterior instability that required bony reconstruction for severe anterior glenoid bone loss were reviewed. In all cases, the length of the anterior glenoid defect exceeded the maximum anteroposterior radius of the glenoid based on preoperative assessment by 3-dimensional CT scan. Surgical reconstruction was performed using an intra-articular tricortical iliac crest bone graft contoured to reestablish the concavity and width of the glenoid. The graft was fixed with cannulated screws in combination with an anterior-inferior capsular repair. RESULTS: At mean follow-up of 33 months, the mean American Shoulder and Elbow Surgeons score was 94, compared with a preoperative score of 65. The University of California, Los Angeles score improved to 33 from 18. The Rowe score improved to 94 from a preoperative score of 28. The mean motion loss compared with the contralateral, normal shoulder was 7 degrees of flexion, 14 degrees of external rotation in abduction, and one spinous process level for internal rotation. All patients returned to preinjury levels of sport, and only 2 complained of mild pain with overhead sports activities. No patients reported any recurrent instability (dislocation or subluxation). The CT scans with 3-dimensional reconstructions obtained 4 to 6 months postoperatively demonstrated union of the bone graft with incorporation along the anterior glenoid rim and preservation of joint space. CONCLUSION: Anatomical reconstruction of the glenoid with autogenous iliac crest bone graft for recurrent glenohumeral instability in the setting of bone deficiency is an effective form of treatment for this problem.     

Spectrum of inherited bleeding disorders from Western India

OBJECTIVE: The study was undertaken to assess the magnitude and diversity of different bleeding disorders in Western India. MATERIALS AND METHODS: 768 cases referred to our Institute for evaluation of an underlying bleeding diathesis were investigated appropriately to detect the cause of the abnormal hemostatic function. RESULTS: 630 patients were diagnosed to have hereditary bleeding diathesis. Amongst these, 598 patients had a coagulation disorder while only 32 patients had a platelet function abnormality. Amongst the coagulation disorders, hemophilia A (70.5%) was the most common disorder followed by hemophilia B (14%) and VWD (10.8%). Glanzman's thrombasthenia (84.3%) was the most common platelet function disorder followed by Bernard-Soulier syndrome (12.5%). Some rare disorders have also been diagnosed. CONCLUSION: In spite of their apparent rarity, India has a substantial number of cases of inherited bleeding disorders. A large number of these patients is referred to many tertiary care institutions. It is therefore desirable that district hospitals must develop their laboratories to detect most of these disorders so that the patients need not travel long distances to get an appropriate diagnosis and proper management. All 1st degree female relatives of severe and moderate hemophilia must get factor assays done because some of them may be vulnerable to post-procedural or post-traumatic bleeding.