Beyhan Demirhan

Effectiveness of human amnion preserved long-term in glycerol as a temporary biological dressing

Human amnion as a temporary biological wound dressing has remained a beneficial and cost-effective means of treating burns in developing countries. The aim of this study was to determine whether human amnion that has undergone long-term preservation in glycerol is an effective biological dressing compared to fresh amnion and glycerol-preserved human skin. Samples of human amnion and skin were preserved in sterile containers of 85% glycerol at 4 degrees C for over a year. Dorsal full-thickness or split-thickness skin wounds were produced in rats. The defects were divided into four areas, each of which was covered with preserved amnion, fresh amnion, preserved skin, or left uncovered as a control. The materials on the wounds were evaluated macroscopically and microscopically after 2, 4, 7, 10 and 14 days. The primary take or adherence of the grafts on full-thickness wounds was evaluated at 4 and 7 days, and material performance was scored based on several macroscopic and microscopic criteria. The bacteria levels reducing effect of the materials were examined by quantitative bacteriology in heavily infected full-thickness scald burn wounds of rats. Qualitative cultures confirmed that the storage conditions the materials were subjected to for over a year were aseptic and that the amnion and skin had maintained their characteristic properties. All materials were found effective on partial-thickness rat wounds as a cover under which re-epithelialization was completed by 7 days. The preserved skin performed better than either preserved or fresh amnion on full-thickness wounds but the performance of preserved amnion was comparable to that of fresh amnion. Glycerol-preserved amnion was found to be as effective as fresh amnion or skin in terms of decreasing bacterial levels in infected rat burn wounds. Amnion stored in glycerol is reliable and effective for a long period of time. Amnion banking could provide an unlimited quantity of biologic dressing for burn treatment at low cost, a factor that is particularly important in developing countries.

Interleukin-12 Receptor β1 Chain Deficiency in a Child with Disseminated Tuberculosis

An 11-year-old girl who presented with disseminated tuberculosis associated with secondary hemophagocytosis received a diagnosis of interleukin-12 receptor beta 1 chain deficiency. This diagnosis of immunodeficiency should, therefore, be considered for children with disseminated tuberculosis, even in the absence of any personal or familial history of prior infection by weakly pathogenic Salmonella and Mycobacterium species.

The presence and prognostic importance of glomerular macrophage infiltration in renal allografts

Aim: The purpose of this study was to analyze the role of intraglomerular macrophage infiltration in human renal allografts by examining biopsies from kidney grafts that were dysfunctional after transplantation. Methods: Eighty-three patients (58 men, 25 women) of a mean age of 30.2 ± 1.4 years were evaluated. In all cases, biopsy specimens were examined for the presence of macrophage infiltration in the glomeruli. The infiltration of these cells was evaluated immunohistochemically using monoclonal antibody CD68, which labels macrophage cytoplasm. 10 renal allograft biopsies with normal histopathology were used as control group. The CD68-positive macrophages in all glomeruli were counted and the glomerular macrophage index (GMI) was calculated. Results: Of the 83 patients, 40 showed acute rejection (AR), 33 showed chronic rejection (CR) and 10 showed cyclosporin A (CsA) toxicity. Only the biopsies of 28 patients stained positive for CD68 in the glomeruli. Neither patients with CsA toxicity nor controls showed intraglomerular macrophages. The CD68-positive group consisted of 7/33 CR and 21/40 AR patients. We observed intraglomerular macrophages in only 6 of the 20 AR cases that responded to steroid therapy (mean GMI 0.3 ± 0.1) and in 15 of the 20 steroid-resistant AR cases (mean GMI 1.7 ± 1.2; p < 0.01). The outcome of grafts that contained intraglomerular macrophages was significantly worse than the outcomes of other grafts noticed during the follow-up. Conclusion: We conclude that the presence of glomerular macrophages can be considered a marker for rejection and is a valuable additional criterion of rejection in the histological examination of renal allograft biopsies. The presence of intraglomerular macrophages indicates that the outcome of the graft will be significantly worse than that of grafts without intraglomerular macrophage infiltration.

Pyogenic granuloma : A rare complication of silicone punctal plugs

To describe pyogenic granuloma formation associated with silicone punctal plugs. A 65-year-old woman with severe dry eye was treated with silicone punctal plugs in both upper and lower puncta. After 14 months of success with the plugs, the patient presented with a fleshy ampullary lesion overlying the plugged superior punctum of her right eye. It was clinically diagnosed as a pyogenic granuloma, and the silicone plug was removed. Since the lesion persisted for 1 month, it was surgically removed. Histopathologic examination confirmed the diagnosis of pyogenic granuloma. A new plug was inserted and tolerated well. The routine use of silicone plugs are recommended as long as patients are informed of possible rare complications.

Chordoid meningioma: Rare variant of meningioma

Chordoid meningioma is a rare variant of meningioma that bears a striking histological resemblance to chordoma and has greater likelihood of recurrence. Although most meningiomas occur in the intracranial, orbital and intravertebral cavities, rare meningiomas have been reported in extracranial organs; thus, it is important to be able to distinguish them from other neoplasms that have similar histology but different biological behavior and therapies. A case of chordoid meningioma in a 48‐year‐old woman who did not have Castlemans syndrome is described in the present report. The patient presented with a mass in her left frontoparietal region, and had been suffering from headaches for many years. Magnetic resonance imaging of the brain demonstrated an expansive lytic lesion in the squamous portion of the left temporal bone. The lesion extended in both directions. Histological examination of the surgical specimen revealed a tumor composed of cords and nests of eosinophilic vacuolated cells embedded in a myxoid matrix. A typical meningiomatous pattern was observed focally, and positive staining of the tumor cells for vimentin and epithelial membrane antigen confirmed the diagnosis of chordoid meningioma.

Impression cytology of the conjunctival epithelium in patients with chronic renal failure

AIMS To assess ocular surface changes in patients with chronic renal failure (CRF), to compare the results with the degree of corneo-conjunctival calcium deposits, and to determine whether precipitation of calcium salts predisposes ocular surface modifications. METHODS Impression cytology from 50 CRF patients on regular haemodialysis and 22 age and sex matched control subjects were studied. Specimens were obtained from the temporal bulbar conjunctiva using cellulose acetate filter paper. The samples were fixed in 95% ethanol, stained with the periodic acid Schiff (PAS) stain, and evaluated by light microscopy and were graded by a masked observer. Corneo-conjunctival calcification was graded by the Porter and Crombie classification. RESULTS In the study group, three patients (6%) disclosed grade 0, 14 patients (28%) grade 1, and 33 patients (66%) grade 2–3 cytological changes. There was a statistically significant difference between the patient and the control groups (p= 0.0007), but no correlation could be found between the impression cytology grades and the calcium deposit grades (p=0.62). CONCLUSION The ocular surfaces of CRF patients differ significantly from those of normal individuals, and it can be detected using impression cytology. These data suggest that the severity of conjunctival changes are not related to the presence or extent of calcium deposition.

Primary extramedullary plasmacytoma of the liver.

Extramedullary plasmacytoma of the liver is a rare tumour, only two cases of which have been reported so far. A third case arising in a 22 year old woman, who presented with abdominal pain and enlargement of the liver, is described. Ultrasound and a computed tomography scan showed a solitary hepatic mass, 12 cm diameter, involving both lobes of the liver. Serum immunoelectrophoresis revealed an IgG kappa monoclonal gammopathy. Histologically, the tumour was composed of mature plasma cells with mild atypia. The plasma cells infiltrated the liver parenchyma and showed kappa light chain restriction. The monoclonal nature of the tumour was also demonstrated by PCR amplification of the immunoglobulin heavy chain genes. There was no evidence of bone involvement and repeated bone marrow aspirates and biopsy specimens were normal. The patient was treated with eight courses of chemotherapy. One year after diagnosis, the patient is well, the size of the tumour has decreased and the paraproteinaemia has disappeared.

Conversion to Sirolimus for Chronic Allograft Nephropathy and Calcineurin Inhibitor Toxicity and the Adverse Effects of Sirolimus After Conversion

BACKGROUND Chronic allograft nephropathy and calcineurin inhibitor toxicity may cause graft loss. After kidney transplantation, especially among those patients with chronic allograft nephropathy, sirolimus may be a good alternative to calcineurin inhibitors. Unlike calcineurin inhibitors, sirolimus is devoid of significant nephrotoxicity, but approximately 30% to 50% of patients on sirolimus therapy display mild or severe adverse effects. We sought to report our experience with sirolimus conversion among patients with chronic allograft nephropathy as well as the mild versus severe adverse effects that limit the drugs use. MATERIALS AND METHODS We analyzed the outcomes of 88 patients (64 men and 24 women) of overall mean age of 35.9 +/- 9.9 years (range, 21-59 years) who had undergone kidney transplantation. Immunosuppressive therapy had been converted from a calcineurin inhibitor to sirolimus because of biopsy-proven chronic allograft nephropathy, calcineurin inhibitor toxicity, or presence of malignancy. We excluded patients with prior acute rejection episodes. Subjects were divided into two groups with respect to their creatinine levels: Group A < 2 mg/dL and Group B >or= 2 mg/dL. After conversion to sirolimus, possible adverse effects of sirolimus were evaluated at the follow-up inset. Each patient underwent a physical examination, and estimation of serum lipid and electrolyte levels as well as hemoglobin concentration. RESULTS At the time of conversion of the 88 renal transplant patients, their mean duration after grafting was 48 +/- 15 months (range, 4-296). The prior treatment consisted of a calcineurin inhibitor, prednisolone, and mycophenolate mofetil. After conversion, the calcineurin inhibitor was stopped and sirolimus was begun. The 48 Group 2 patients (34 men, 14 women) of overall mean posttransplant time of 22.7 +/- 14.6 months who underwent conversion displayed a mean serum creatinine increase to 3.2 +/- 1.4 mg/dL, including 17 subjects who underwent rejection. The 40 Group 1 patients (30 men, 10 women) with a mean overall posttransplant period of 67.6 +/- 49.9 months showed an fall in serum creatinine level to 1.4 +/- 0.5 mg/dL among only 3 patients. While 5/88 patients showed no increase in proteinuria (5.6%); 83 (94.4%) did experience it. Proteinuria increased from a mean of 192 +/- 316 to 449 +/- 422 mg/d. Only three patients displayed heavy proteinuria (>3 g/d); sirolimus was discontinued for this reason. Proteinuria was well controlled in the other patients with angiotensin-converting enzyme and/or angiotensin II receptor inhibitor agents. After sirolimus conversion, serum cholesterol levels increased from 187 +/- 42 to 214 +/- 52 mg/dL, and serum triglyceride levels increased from 161 +/- 61 to 194 +/- 102 mg/dL. All but four patients responded to statin therapy, with serum lipid levels falling to acceptable levels. Another four patients developed unilateral lower extremity edema with sirolimus discontinued for this reason. One patient displayed generalized arthralgia. CONCLUSION Chronic allograft nephropathy or calcineurin inhibitor toxicity can lead to loss of graft kidney function. Calcineurin inhibitor toxicity can lead to chronic allograft nephropathy. Patients with a low baseline serum creatinine level who undergo sirolimus conversion showed stabilized kidney function. Late conversion of patients with a serum creatinine above 2 mg/dL face a risk of graft failure. Sirolimus displayed a limited incidence of serious adverse effects; mild or moderate adverse effects, such as hyperlipidemia and proteinuria, were easily controlled with countermeasure therapy.

A family with Jeune syndrome.

Abstract  Jeune syndrome is a rare autosomal recessive disease characterized by narrow thoracic cage and short-limbed dwarfism. Seventy percent of affected individuals die in early childhood from pulmonary hypoplasia and respiratory distress due to the small size of the thorax. Growth retardation and chronic renal insufficiency due to nephronophthisis may occur in patients who survive the respiratory failure. We report a family that exhibited clinically heterogeneous features of Jeune syndrome. The 6-year-old male proband presented with skeletal deformities and chronic renal failure. A kidney biopsy revealed that nephronophthisis was the cause of the patient’s kidney failure,and we diagnosed Jeune syndrome. A retrospective diagnosis of Jeune syndrome was also established for the proband’s older sister, who haddied of renal failure at 8 years of age. The oldest female child in the family alsohad thoracic deformity, and the father and paternal uncle were both of short stature and exhibited brachydactyly. Their renal function and blood pressure were normal. The findings in this family are important in that they demonstrate the clinical heterogeneity of Jeune syndrome and underline the association of renal disease with this syndrome.

Vascular Endothelial Growth Factor Expression and Cyclosporine Toxicity in Renal Allograft Rejection

The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF‐α, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow‐up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF‐α expressions (p < 0.001). VEGF expression increased with increasing expression of TNF‐α (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow‐up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.