PHEOCHROMOCYTOMA, THE GREAT MASQUERADER, PRESENTING AS REVERSIBLE CARDIOMYOPATHY: PRIMUM NON NOCERE.

Background: Pheochromocytoma, the great masquerader, can have a varied spectrum of clinical manifestations. It can often cause a diagnostic challenge despite the availability of modern investigation modalities. Case: We present the case of a 38-year-old male who presented with uncontrolled hypertension for the past 10 years and heart failure for one year. The diagnosis of pheochromocytoma was missed in the initial setting, leading to a biopsy of the retroperitoneal mass. Fortunately, the patient survived the procedure. Subsequently, with the involvement of a multi-disciplinary team, he was optimized for surgery under strict cardiac monitoring. After the complete excision of the tumour, he showed significant improvement not only in his clinical symptoms but also in his cardiac status. Conclusions: This case emphasizes the age-old medical phrase of 'Primum non nocere or first, do no harm'. Any invasive procedure in a pheochromocytoma can lead to a massive release of catecholamines causing a hypertensive crisis, pulmonary oedema, and even cardiac arrest. Any young patient presenting with hypertension or heart failure should be investigated for secondary causes. Cardiomyopathy due to pheochromocytoma is because of catecholamine overload and usually reverses or improves after curative surgery.

An observational study of the efficacy of azithromycin in erythema annulare centrifugum.

Erythema annulare centrifugum (EAC) is a form of figurate erythema consequent to a cutaneous hypersensitivity reaction to an underlying agent. In the present study, we aimed to assess the role of oral azithromycin in cases of idiopathic EAC. We performed an open trial of azithromycin in 10 patients with idiopathic EAC. Histopathological examination of biopsies was performed to exclude any alternative diagnosis and to assess the depth of the infiltrate. Patients were administered oral azithromycin 250 mg once daily until clinical resolution of the disease, and followed up regularly to monitor for possible relapse. Histopathological examination of the 10 biopsies revealed superficial pattern in 3, deep pattern in 2 and mixed pattern in the remaining 5. Of the 10 patients, 8 responded to azithromycin 250 mg, with no relapse during follow-up. Oral azithromycin might be a promising therapy in cases of idiopathic EAC. Cases with a superficial pattern respond earlier than cases with a deep pattern.

Variola virus F1L is a Bcl-2-like protein that unlike its vaccinia virus counterpart inhibits apoptosis independent of Bim.

Subversion of host cell apoptosis is an important survival strategy for viruses to ensure their own proliferation and survival. Certain viruses express proteins homologous in sequence, structure and function to mammalian pro-survival B-cell lymphoma 2 (Bcl-2) proteins, which prevent rapid clearance of infected host cells. In vaccinia virus (VV), the virulence factor F1L was shown to be a potent inhibitor of apoptosis that functions primarily be engaging pro-apoptotic Bim. Variola virus (VAR), the causative agent of smallpox, harbors a homolog of F1L of unknown function. We show that VAR F1L is a potent inhibitor of apoptosis, and unlike all other characterized anti-apoptotic Bcl-2 family members lacks affinity for the Bim Bcl-2 homology 3 (BH3) domain. Instead, VAR F1L engages Bid BH3 as well as Bak and Bax BH3 domains. Unlike its VV homolog, variola F1L only protects against Bax-mediated apoptosis in cellular assays. Crystal structures of variola F1L bound to Bid and Bak BH3 domains reveal that variola F1L forms a domain-swapped Bcl-2 fold, which accommodates Bid and Bak BH3 in the canonical Bcl-2-binding groove, in a manner similar to VV F1L. Despite the observed conservation of structure and sequence, variola F1L inhibits apoptosis using a startlingly different mechanism compared with its VV counterpart. Our results suggest that unlike during VV infection, Bim neutralization may not be required during VAR infection. As molecular determinants for the human-specific tropism of VAR remain essentially unknown, identification of a different mechanism of action and utilization of host factors used by a VAR virulence factor compared with its VV homolog suggest that studying VAR directly may be essential to understand its unique tropism.

'Congenital follicular melanocytic naevi': a more appropriate term for spotted grouped pigmented naevi.

We report two patients with an uncommon form of pigmented naevus consisting of grouped follicular papules. A biopsy taken from the lesions showed multiple naevus cells, predominantly around the hair follicles, with sparing of the eccrine glands. The clinicohistopathological term given for this condition is 'spotted grouped pigmented naevi type I', and has rarely been reported. We discuss the unusual morphology and differential diagnosis of this condition, and suggest that the term 'congenital follicular melanocytic naevi' is more appropriate for this presentation.

Medial dislocation of the medial meniscus.

We present the first reported case of symptomatic medial dislocation of the medial meniscus in a patient who had no previous history of trauma and who had an otherwise normal knee. The treatment of instability of the medial meniscus is controversial and studies have indicated that certain individuals without a firm meniscal bony insertion may be predisposed to meniscal dislocation. In our patient, the meniscal instability interfered with daily activities. Operative stabilisation by reconstruction of the meniscotibial ligaments cured the symptoms.

Analysis of results of surgical treatment of posttraumatic stiff elbow.

BACKGROUND: Surgical management of posttraumatic elbow stiffness has been reported with poor outcome following treatment. Sequential release in earlier stages of stiffness yielded much better results. The goal of our study was to assess the outcome in improvement of the range of motion of the elbow after surgical release and to analyze a tailor-made approach according to individual needs to yield good result. MATERIALS AND METHODS: A prospective study was conducted in 47 cases of elbow stiffness due to various types of injuries. All the cases were treated with sequential release if there was no progress after adequate supervised conservative management except in unreduced dislocations. All the cases were followed up for a minimum period of 24 months. Overall outcome was rated with the functional scoring system by Mayo Clinic Performance Index. RESULTS: Twenty-five (44.68%) out of 47 patients had excellent results with a mean preoperative range of motion of 33.9 degrees and postoperative range of motion of 105 degrees with net gain in range of motion of 71.1 degrees ('t' test value is 19.27, P < 0.01). None of the patients had elbow instability. Patients not having heterotopic ossification, who underwent surgery from three to six months post injury had a mean gain of 73.5 degrees. In patients who waited for more than six months had mean gain of 66.8 degrees. However, the results in cases having heterotopic ossification followed a slightly different pattern. In cases where release was performed from three months to six months had mean gain of 77.5 degrees. Cases in which release was performed after six months had gain of 57.1 degrees. CONCLUSIONS: In cases of posttraumatic elbow stiffness after a failed initial conservative treatment, early arthrolysis with sequential surgical soft tissue release yields good result than delayed surgery.

Early changes in gene expression that influence the course of primary glomerular disease.

Serial changes in glomerular capillary loop gene expression were used to uncover mechanisms contributing to primary glomerular disease in rat models of passive Heymann nephritis and puromycin nephrosis. Before the onset of proteinuria, podocyte protein-tyrosine phosphatase (GLEPP1) expression was transiently decreased in the nephrosis model, whereas the immune costimulatory molecule B7.1 was stimulated in both models. To relate these changes to the development of proteinuria, the time of onset and intensity of proteinuria were altered. When the models were induced simultaneously, proteinuria and anasarca occurred earlier with the collapse of glomerular capillary loops. Upregulation of B7.1 with the downregulation of GLEPP1, Wilms' tumor gene (WT1), megalin, and vascular endothelial growth factor started early and persisted through the course of disease. In the puromycin and the combined models, changes in GLEPP1 expression were corticosteroid-sensitive, whereas B7.1, WT1, vascular endothelial growth factor, and most slit diaphragm genes involved later in the combined model, except podocin, were corticosteroid-resistant. There was a very early increase in the nuclear expression of podocyte transcription factors ZHX2 and ZHX1 that may be linked to the changes in gene expression in the combined proteinuric model. Our studies suggest that an early and persistent change in mostly steroid-resistant glomerular gene expression is the hallmark of severe and progressive glomerular disease.

Aminopeptidase A: a nephritogenic target antigen of nephrotoxic serum.

BACKGROUND: We investigated potential targets of antibody-mediated glomerular injury induced with a noncomplement binding fraction of sheep anti-rat nephrotoxic serum (NTS). This model is characterized by severe complement- and leukocyte-independent proteinuria within 24 hours of NTS injection into rats. METHODS: NTS-reactive glomerular cell and matrix proteins were identified by immunoprecipitation, Western blot analysis, protein sequencing, cDNA library screening, and enzyme-linked immunosorbent assay. Proteinuria was measured in rats injected with NTS from which reactivity against type IV collagen had been removed by immunoadsorption, and antibodies were eluted from the glomeruli of proteinuric rats that had been injected with unabsorbed NTS. Having identified aminopeptidase A (APA) as a major target of NTS, we studied the effect of NTS and anti-APA on mouse glomerular epithelial cells in culture. RESULTS: NTS identified several podocyte and matrix proteins; however, APA was the only cell surface protein reactive with antibodies eluted from the glomeruli of rats injected with NTS. Although the eluate also contained reactivity to the noncollagenous domains of alpha1 and alpha3 chains of type IV collagen, immunodepletion of these antibodies did not diminish the ability of NTS to cause proteinuria. We also documented the surface expression of APA on mouse glomerular epithelial cells in culture, and found that NTS and specific anti-APA antibodies induce a time- and temperature-dependent redistribution of the antigen. CONCLUSIONS: APA, a type II integral membrane metallopeptidase, is a major target of NTS in vivo and is known to be present on the surface of podocytes. NTS-induced proteinuria is independent of reactivity to known nephritogenic matrix proteins. These findings, in combination with previous studies showing that monoclonal anti-APA antibodies induce severe proteinuria in mice, suggest that anti-APA antibodies are responsible for complement-independent proteinuria in this model.

Effect of glycemic control and vitamin E supplementation on total glutathione content in non-insulin-dependent diabetes mellitus.

Thirty patients with non-insulin-dependent diabetes mellitus were selected for the study. 15 age-matched healthy volunteers served as controls. Serum malonaldehyde, total glutathione, and vitamin E levels were estimated before and after glycemic control and after 4 weeks of vitamin E supplementation. Both total glutathione and vitamin E levels increased after glycemic control and showed an increase after vitamin E supplementation. Malonaldehyde levels lowered after glycemic control, but remained higher than controls. Since vitamin E supplementation significantly decreased oxidative stress in the present study, it may play a role in reducing free-radical-induced oxidant injury in diabetes mellitus.

Evaluation of oxidative stress before and after control of glycemia and after vitamin E supplementation in diabetic patients.

The present study evaluates the presence of oxidative stress in the uncontrolled diabetic state. Glycemic control reduced the oxidative stress, but total normalization of the parameters of oxidative stress was not achieved, indicating continued oxidant injury despite optimal control of the diabetes. Vitamin E supplementation for 4 weeks in these patients further reduced the oxidative stress, suggesting that vitamin E supplementation might be helpful in reducing free-radical-induced oxidant injury.

Evaluation of oxidative stress before and after haemodialysis in chronic renal failure.

OBJECTIVE: To evaluate the oxidative stress before and after haemodialysis in chronic renal failure patients. METHODS: A prospective study comprising of 22 patients of CRF who have to receive their first haemodialysis. All patients were subjected to standard four hours haemodialysis. The parameters of oxidative stress i.e. erythrocyte malonaldehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) were measured before and after haemodialysis. RESULTS: The value of mean erythrocyte MDA (9.40 +/- 3.36 mumol/L) and SOD (617 +/- 64.33 units/ml) were significantly higher in patients of CRF before haemodialysis than in controls (p < 0.001). The mean GSH levels were significantly lower (451 +/- 63.91 micrograms/ml) in patients than in controls before haemodialysis (p < 0.001). After haemodialysis MDA levels further increased (12.27 +/- 4.38 mumol/L), SOD levels decreased (458 +/- 69.58 EU/ml) and GSH levels further decreased (396 +/- 41.41 micrograms/ml) (p < 0.001). CONCLUSIONS: There was an evidence of oxidative stress in patients of CRF before haemodialysis which increased further after haemodialysis, the mechanisms of which is not delineated. The procedural factors may be contributing in the increased oxidative stress after haemodialysis.

An evaluation of oxidative stress in diabetes mellitus during uncontrolled and controlled state and after vitamin E supplementation.

OBJECTIVE: The study was conducted on 50 patients (10 insulin dependent diabetes mellitus (IDDM) and 40 non-insulin dependent diabetes mellitus (NIDDM) of recently diagnosed diabetes mellitus. The main objectives of the study were: 1. To evaluate oxidative stress at uncontrolled stage. 2. To evaluate the effect of optimal control on oxidative stress irrespective of type of drug therapy used. 3. To further evaluate the effect of vitamin E supplementation on oxidative stress after achieving optimal control. This was done in order to explore anti-oxidant effect of vitamin E. METHODS: Fifty patients of uncontrolled diabetes of less than 1 year duration and without any overt complications were studied. The parameters of oxidative stress included malonyl-di-aldehyde (MDA), reduced glutathione and vitamin E levels in the blood. They were done at three stages i.e. (a) In uncontrolled stage, (b) At controlled stage and (c) After 4 weeks of vitamin E supplementation in dosage of 400 mg daily. The parameters of control included fasting blood sugar < or = 140 mg%, post prandial < or = 200 mg and HbA1c < or = 7% (analysed by prepared kit). RESULTS: The significantly raised levels of MDA and decreased levels of reduced glutathione and vitamin E during uncontrolled stage of diabetes indicated free radical stress inducing lipid peroxidation. The significant fall of MDA and rise in reduced glutathione and vitamin E levels in blood after optimal control revealed its beneficial effect on oxidative stress. The levels were not normalised but still stayed higher than controls. After 4 weeks of vitamin E supplementation, further fall in MDA and rise in reduced glutathione suggested beneficial effect of vitamin E over and above the optimal control. Vitamin E estimation in blood at this stage did not constitute parameter of oxidative stress as it was provided from outside but was done to know the compliance of patients. Normalisation or near normalisation was not achieved with vitamin E therapy indicating persistence of oxidative stress. CONCLUSION: There was an evidence of oxidative stress in diabetes which decreased with optimal control and further declined after vitamin E supplementation indicating anti-oxidant effect of vitamin E alone. Normalisation of oxidative stress was not achieved. A further study is desired to study the effect of vitamin E for longer period at least 3-6 months before a definite conclusion is drawn.

Lowered antioxidant status of red blood cells in post-parturient haemoglobinuria of buffaloes.

The antioxidant status of the red blood cells of buffaloes (n = 20) suffering from post-parturient haemoglobinuria (PPH) was assessed by comparing their tocopherol (vitamin E) and reduced glutathione contents with those of red blood cells from apparently healthy buffaloes (n = 20). The red cell tocopherol content of the diseased buffaloes (1.76 +/- 0.11 micrograms/ml) was significantly (p < 0.01) lower than that of healthy buffaloes (2.45 +/- 0.14 micrograms/ml). This may be the first report comparing the concentration of tocopherol in the red blood cells of buffaloes suffering from PPH and apparently healthy buffaloes. There was a drastic reduction in the reduced glutathione content in the red cells of haemoglobinuric buffaloes (23.74 +/- 2.86 mg%) compared to the healthy control buffaloes (73.71 +/- 3.87 mg%). The diseased buffaloes also exhibited severe hypophosphataemia. These findings suggest that an impaired or insufficient antioxidant potential of the red blood cells in this disease in buffaloes is associated with the phosphorus deficiency.

Autologous bone grafting in staged scoliosis surgery. The patient as bone bank.

STUDY DESIGN: A prospective clinical study in which autologous rib graft, harvested during the thoracotomy in staged scoliosis correction, is stored within the patient for use during the second stage (posterior intrumentation and fusion). OBJECTIVE: To determine whether the bone stored by this technique is biologically viable and microbiologically safe. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, this method of storage of bone has never been described previously. METHODS: During the first operation, the excised rib was divided into 3-5 cm fragments and stored in a sub-muscular plane adjacent to the posterior elements of the spine before closure. The graft was then retrieved at the second stage. Samples were sent for histologic and microbiologic examination before implantation. RESULTS: On histologic examination, more than 50% of the osteocytes retained their basophilic staining, indicating that they were viable. In addition, osteoclastic activity was notably absent. There was no significant bacterial contamination of the samples. Clinically, all patients achieved satisfactory bone fusion. CONCLUSION: Homeostatic equilibrium in humans provides the ideal environment in which bone graft can be stored. There is no increased risk of infection, and the osteogenic potential of the graft is retained.

Atraumatic dislocation of the trapeziometacarpal joint secondary to osteoarthritis.

We report a case of atraumatic dislocation of the trapeziometacarpal joint secondary to osteoarthritis. An attritional rupture of the anterior oblique carpometacarpal ligament is thought to have occurred, allowing complete dislocation which has led to a reduction in the patient's pain.

A critical evaluation of anti-peroxidant effect of intravenous magnesium in acute aluminium phosphide poisoning.

The anti-peroxidant effect of intravenous magnesium was evaluated in 50 patients with acute aluminium phosphide poisoning. The patients were divided into two groups, one who received magnesium sulphate therapy (Group I) and the other who did not (Group II). The clinical and biochemical parameters in both groups were comparable. Finding of increased mean malonyl-di-aldehyde (MDA) levels in group I (3.18 +/- 0.93 micromol/L) and group II (3.15 +/- 0.78 mmol/L) combined with low blood levels of reduced glutathione (18.5 +/- 1.6 mg/dl in group I) and (17.8 +/- 1.4 mg/dl in group II) indicated oxidative stress leading to accelerated lipid peroxidation in the early phase (0-6 h) of AlP poisoning. A significant fall in MDA levels was observed after 2 h in the magnesium treated group (group I) compared to the non-treated group (group II) and levels became normal between 48-72 h. Similarly reduced glutathione started recovering between 12-24 h which became significant after 24 h and full recovery took place between 48-72 h in the magnesium treated group (group I). Both these parameters suggested an anti-peroxidant effect of magnesium. There was also a slight fall in MDA levels and a rise in reduced glutathione in the non-treated group II patients. This could be due to elimination of phosphine (PH3). We hypothesize that oxidative stress in AlP poisoning buffered the magnesium leading to a transient fall in magnesium and magnesium dependent GSH, resulting in increased susceptibility of oxygen free radical injury and accelerated lipid peroxidation. The fall in MDA and slower rise in GSH in group I than in group II suggested magnesium combated free radical stress slowly and independent of elimination of phosphine. This hypothesis was further strengthened by similar observations when both these parameters were compared in survivors in both groups. Mortality was higher in group II than in group I (44 per cent vs 20 per cent) and was probably related directly to oxidative stress.