Thrombotic microangiopathy in association with cytomegalovirus infection in a renal transplant patient: a new treatment strategy

BACKGROUND: Cytomegalovirus (CMV) associated with thrombotic microangiopathy (TMA) in transplant patients has not been extensively described. This case illustrates an association between CMV and TMA in a transplant patient with resolution of the latter after treatment of the CMV. METHODS AND RESULTS: At 6 weeks after renal transplantation, a 57-year-old woman presented with TMA. Cyclosporine was discontinued, and plasmapheresis was started. However, the patient continued to deteriorate and developed CMV pneumonitis. Plasmapheresis was discontinued, and intravenous ganciclovir was initiated. Both the TMA and the CMV resolved after initiation of the ganciclovir. CONCLUSION: This case identifies another potential etiological factor in the development of TMA after renal transplantation. It is the first reported case of TMA being cured with treatment of CMV.     

Thrombotic microangiopathy associated with Streptococcus pneumoniae bacteremia: case report and review

Thrombotic microangiopathy, a disease within the clinical spectrum of thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, was recognized in a previously healthy 50-year-old woman who presented with pneumococcal bacteremia complicated by thrombocytopenia, microangiopathic hemolytic anemia, renal failure, and disorientation. After treatment with plasma exchange and antibiotics, the patient's clinical condition improved. Discontinuation of plasma exchange resulted in a relapse of thrombocytopenia and microangiopathic hemolytic anemia that responded to reinitiation of this intervention. The production of the enzyme neuraminidase by Streptococcus pneumoniae is thought to contribute to the pathogenesis of the thrombotic process. Although pneumococcal infection has been associated with hemolytic-uremic syndrome in children, review of the literature on adults revealed only one such case (in a patient who had undergone splenectomy in the remote past). This report therefore documents an unusual complication of pneumococcal bacteremia in an immunocompetent adult.     

Outcome of plasma exchange therapy in thrombotic microangiopathy after renal transplantation

Thrombotic microangiopathy (TMA) in renal transplant recipients is commonly associated with calcineurin inhibitors (CNIs), though several factors such as vascular rejection, viral infections and other drugs may play a contributory role. We report a series of 29 patients with TMA, all of whom were on CNIs. Though plasma exchange (PEx) is widely used to treat TMA, therapeutic guidelines are not well defined. All our patients were treated with PEx and discontinuation of CNIs. Thrombotic microangiopathy was diagnosed at a median of 7 days post-transplant. The mean decrease in Hgb and platelets during TMA was 66% and 64%, respectively, and peak serum creatinine during TMA was 7.4 +/- 2.9 mg%. Mean duration of PEx therapy was 8.5 (range 5-23) days. Recovery of platelet count to 150K/mcL and Hgb to 8-10 g/dL were used as endpoints for PEx. Twenty-three/29 (80%) patients recovered graft function after PEx. Twenty/23 (87%) patients who recovered were placed back on CNl. Nineteen/20 (95%) patients tolerated reinstitution of CNl without recurrence of TMA. In post-transplant TMA, PEx was associated with a graft salvage rate of 80%, reversal of hematological changes can be used as the endpoint for PEx therapy and CNl can be reintroduced without risk of recurrence in the majority of patients.     

Oscillatory insulin secretion after pancreas transplant

In vivo studies of beta-cell secretory function have demonstrated the existence of rapid insulin oscillations of small amplitude recurring every 8-15 min in normal subjects. This study evaluated the effects of pancreas transplant on rapid insulin oscillations. Samples for glucose, insulin, and C-peptide were drawn during constant glucose infusion at 2-min intervals for 90 min from six successful Px patients with type I diabetes mellitus, from six normal nondiabetic control subjects, and from three Kx subjects. A computerized algorithm (ULTRA) was used for pulse detection. In the Px group, the average insulin pulse period was significantly shorter than in both the control and Kx groups (Px 8.1 +/- 0.5, control 12.5 +/- 0.7, Kx 12.4 +/- 0.5 min, P < 0.0005). By contrast, the C-peptide pulse periods (Px 16.8 +/- 2.3, control 14.7 +/- 1.2, Kx 15.3 +/- 1.5 min) were similar in the three groups. Spectral analysis confirmed that the frequency of the insulin pulses was increased in the Px group. The absolute amplitude of the insulin pulses was greater in the Px group (P < 0.001) while the amplitude of the C-peptide pulses did not differ between the groups. Cross-correlation analysis demonstrated maximal correlation coefficients at a lag of 0 min between insulin and C-peptide (control r = 0.33, P < 0.0001; Kx r = 0.17, P = 0.06) and between insulin and glucose (control r = 0.21, P < 0.001; Kx r = 0.20, P < 0.02) in the control and Kx groups, respectively, whereas no significant correlations were observed at any lag in the Px group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathogenesis of diabetic microangiopathy

Several are the recent experimental data regarding the pathogenesis of diabetic microangiopathy, even if the comprehensive picture of this condition is still rather incomplete. The functional and structural alterations of several organs involved (first of all kidney and retina) are especially dependent on the activation of the polyol pathway and on the increase of the nonenzymatic glycosylation. An important determinant of diabetic microangiopathy is the increase of permeability, at first charged especially to the haemodynamic alterations and partly reversible, and later supported by irreversible variations of the cellular and extracellular components of the vascular wall. Genetic factors certainly contribute to the explanation of the diverse gravity of microvascular damage in diabetic patients, even if the mechanisms by which they interfere are only partly known. Furthermore, the links between arterial hypertension and diabetic nephropathy, and also the reduction in glycosaminoglycans in the basal membranes are perhaps genetically originated.     

Intestinal motility after massive small bowel resection

To evaluate intestinal motility after 80% massive distal small bowel resection (MSBR), we continuously monitored interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gage force transducers in conscious beagle dogs before, and at 0-4 weeks and 8-13 months after the surgery. Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) occurred at longer intervals in the short-term after 80% MSBR than in controls, and were simulated in long-term that in controls. MMCs arising from the duodenum were often migrated to the proximal jejunum, the jejunum above the anastomosis, and to the terminal ileum beyond the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment in the short-term, and had not recovered even long after the operation. The duration of the postprandial period without duodenal MMCs was prolonged significantly in the short-term, and still remained longer in the long-term than in controls. These findings suggest that changes in gut motility after MSBR tend to compensate for the shorter intestine and maintain small bowel absorption early postoperatively, and adaptations of motility would occur over the long-term to increased intestinal absorption.     

Thrombotic angiokeratoma circumscriptum simulating melanoma

Three patients with solitary angiokeratomas, two of the circumscribed type (Fabry) and one of the Mibelli type, are described to show that when extensive thromboses develop in an angiokeratoma, this nodular bluish-black lesion may clinically simulate a nodular melanoma.     

Pregnancy after heart transplant: update and case report

Based on their ability to induce leukocyte chemotaxis and adhesion to endothelial cells (ECs), chemokines have been implicated in driving inflammatory leukocyte emigration. Recently, it was suggested that chemokines can accomplish their pro-emigratory role more effectively while being bound to the luminal surface of the ECs. Previously, such binding was demonstrated in situ in human skin for the prototype alpha-chemokine interleukin (IL)-8. Here we used an in situ binding assay to investigate the binding characteristics of several beta-chemokines in intact human skin. RANTES, MCP-1, and MCP-3 bound, similar to IL-8, in a specific saturable manner to the ECs of venules and small veins but not arteries or capillaries. RANTES inhibited MCP-1 and MCP-3 binding and vice versa, indicating that the EC binding sites are shared among these beta-chemokines; moreover, IL-8 and RANTES cross-competed for each other's binding, suggesting that the same chemokine binding sites are used by members of alpha- and beta-chemokine subfamilies. Conversely, MIP-1alpha did not bind to the ECs and did not compete for binding of RANTES. Analogous to IL-8, all of the tested beta-chemokines bound to the resident dermal cells. As a novel aspect of chemokine interaction with cells in normal skin, we observed specific, saturable binding of RANTES, MCP-1, and MCP-3 but not MIP-1alpha or IL-8 to the ECs of dermal afferent lymphatic vessels. RANTES, MCP-1, and MCP-3 also cross-competed for each other's binding to lymphatics, suggesting a common binding site with a novel chemokine binding profile. We suggest that the chemokine binding to the ECs of lymphatics may be involved in the process of leukocyte entry into the afferent lymphatic vessels.     

MR imaging findings after transplant surgery for Parkinson disease

There is a strong correlation between gingival inflammation and clinical and sub-clinical ascorbic acid deficiency. This has created a demand for a handy diagnostic test to detect the ascorbic acid deficiency. The aim of this work was to find out the efficacy of one such test, i.e. the modified Lingual Ascorbic Acid Test (LAAT). To find out the significance of ths LAAT, it was compared with plasma ascorbic acid levels and then confirmed statistically. Our findings suggest that with this simple, reliable and inexpensive method, the dental practitioners can conveniently assess the ascorbic acid status of their patients.