Antithymocyte globulin use for treatment of biopsy confirmed acute rejection is associated with prolonged renal allograft survival

Antithymocyte globuline (ATG) and OKT3 have been used for treatment of severe biopsy confirmed acute renal allograft rejection (BCAR). We report results on graft and patient survival including 399 subjects diagnosed with BCAR treated with either ATG or OKT3. Multivariable analyses including Banff scores were performed following three different strategies to account for confounding variables. Fifty per cent of subjects in the OKT3 group had a functioning graft 6.3 years after diagnosis of BCAR, but 74% of ATG patients' grafts were still functioning at that time point (log rank P  = 0.006). Median actual graft survival was only 4.6 years in the OKT3 subjects, but 9.5 years for ATG-treated patients (log rank P  = 0.004). Multivariable analysis revealed that the risk for functional graft loss was significantly elevated in the OKT3 compared to ATG patients (HR = 1.79, 95% CI 1.06–3.02, P  = 0.029). The risk for actual graft loss, counting death as event, was also significantly elevated in the OKT3 patients (HR = 1.73, 95% CI 1.09–2.74, P  = 0.019). The hazard of death was not different between the groups (HR = 1.55, 95% CI 0.87–2.77, P  = 0.137). These data suggest that rejecting renal allografts treated with ATG exhibit longer graft survival than OKT3 treated transplant kidneys. Causal inference, however, cannot be drawn from this associational study.     

Intraoral Perineurioma,Soft Tissue Type: Report of Five Cases,Including 3 Intraosseous Examples,and Review of the Literature

Soft tissue type perineuriomas (STP) are uncommon tumors, oral examples being very rare. They have been described in the mandible, gingiva, lips, retrotonsillar mucosa and maxillary vestibule. Herein, we report the clinicopathologic features of five STP, two affecting the buccal mucosa and three the mandible. Three patients were women and two men. All tumors were characterized by a proliferation of cytologically bland, mitotically inactive spindled cells with round, ovoid or spindled nuclei, embedded in a variably collagenous and myxoid matrix. Interestingly, two mandibular tumors featured psammoma bodies and one, in addition, contained irregular calcifications. Tumor cells showed the immunohistochemical profile of perineurial cells including epithelial membrane antigen, Glut-1, claudin-1 and collagen type IV. S100 and neurofilament proteins were not expressed by the tumor cells. A few minute, peripherally situated, entrapped nerves were identified. All tumors were reported gross-totally excised and no recurrences have taken place. The clinical characteristics of STP are summarized and its differential diagnosis relative to other spindle cells tumors and meningioma is discussed.     

Pseudotumors in Small-Head Metal-on-Metal Total Hip Arthroplasties at a Minimum Follow-Up of 20 Years

BackgroundMetal-on-metal (MOM) surfaces in total hip arthroplasty (THA) have been used widely. Serum cobalt and chromium levels have been the standard investigation for follow-up examinations, but magnetic resonance imaging (MRI) with metal artifact reducing sequences has shown good results in detecting pseudotumors. The aim of this study is to survey a significant correlation among MRI findings, serum metal levels, and clinical scores in patients with small-head MOM implants and if serum cobalt and chromium levels are sufficient in detecting patients with pseudotumors in the long-term follow-up.MethodsAt a minimum follow-up of 20 years, 26 patients (29 THAs) of the original 98 patients (105 THAs) included in this study between November 1992 and May 1994 were available for follow-up examination. Clinical scores, serum metal ion levels, and MRIs were obtained.ResultsWe found mean serum cobalt levels of 1.87 μg/L (±3.44) and chromium levels of 2.23 μg/L (±2.96) and very good clinical and functional results (mean Harris Hip Score 88.6) in the long-term follow-up. Pseudotumors were detected in MRIs of 21 hips. There were no significant differences between patients with or without pseudotumors regarding serum metal levels and the correlation for clinical outcome scores, demographic data, and cup inclination. The cumulative rate of survival was still at 91.4% at 22.8 years.ConclusionThis study presents the first published data on small-head MOM hips, comparing metal ion levels, pseudotumors, clinical, and radiological results in a follow-up period of more than 20 years and reveals that serum metal levels are not significantly higher in patients with pseudotumors.Level of EvidenceTherapeutic Level III     

Versatility of vertical rectus abdominis musculocutaneous flaps

The purpose of the study was to demonstrate a variety of indications for the vertical rectus abdominis musculocutaneous (VRAM) flap with respect to donor-site morbidity and alternative procedures. Fifteen VRAM flaps were performed in 15 patients during a 4-year period. The average age of patients was 58 years (range, 34-76 years). Inferiorly based VRAM flaps were used for defect coverage after tumor resection and for penile reconstruction in 7 cases. Superiorly based VRAM flaps were performed in 7 cases for reconstruction of osteocutaneous defects following sternal osteomyelitis and tumor resection. Arterial and venous "supercharging" was necessary in one case. One free VRAM flap was performed in a patient suffering from an osteocutaneous defect after resection of a malignant melanoma metastasis with infiltration of the brain and skull. The reconstructive goals were achieved in all cases using VRAM flap procedures. No total flap loss occurred. Minor complications as well as abdominal wall bulging and hernias were observed in four cases. The pedicled VRAM flap provides a reliable tool for coverage of large soft-tissue defects of the chest wall, groin, hip, and perineum even in a high-risk population, in which a safe and fast forward flap procedure is the primary reconstructive goal. Arterial and/or venous supercharging may be necessary, particularly in superiorly based VRAM flaps. An inferiorly based VRAM flap is a reliable tool for phalloplasty under special circumstances. The indication for free VRAM flaps is given in rare clinical situations. Stabilization of the donor site using artificial mesh is highly recommended.     

Hypercalciuria in patients with CLCN5 mutations

Hypercalciuria is regarded as a characteristic symptom of Dent disease, an X-linked recessive tubulopathy characterized by low molecular weight (LMW) proteinuria, nephrocalcinosis/nephrolithiasis, and progressive renal failure due to mutations in the CLCN5 gene. As the presence of hypercalciuria may affect the decision to consider a CLCN5 mutation in the differential diagnosis, the phenotypic spectrum and the relative frequency of hypercalciuria in patients with CLCN5 mutations was determined. We assessed renal calcium excretion in 34 male patients with proven CLCN5 mutations, who had been referred because of LMW proteinuria and at least one additional symptom of Dent disease. Hypercalciuria was defined as renal calcium excretion exceeding 0.1 mmol/kg per day. Data obtained were compared with all series of CLCN5-positive patients identified by a systematic literature survey. In 7 of our 19 families, at least 1 affected male had normal calcium excretion. Hypercalciuria was observed in 22 of 31 patients tested (71%) compared to 85 of 90 (94.4%) in series from Europe and North America and 74.4% from Japan. LMW proteinuria was present in all CLCN5-positive patients; 25% of the patients in European and North American series, 45% of the Japanese, and 41% in the present series had only two of the four principal symptoms of Dent disease. Therefore, a CLCN5 mutation should be considered irrespective of the presence of hypercalciuria in a patient with LMW proteinuria and one additional symptom of Dent disease.     

Gadolinium-enhanced MR angiography of the breast: Is breast cancer associated with ipsilateral higher vascularity?

The aim of this study was to assess a possible association between breast malignancy and ipsilateral higher vascularity on gadolinium-enhanced MR angiography. One hundred six patients were examined by dynamic gadolinium-enhanced 3D MR imaging. Magnetic resonance angiographic views were generated by image subtraction and maximum intensity projection. The study included 85 patients with unilateral malignant breast neoplasms and 21 with unilateral benign lesions. Three blinded readers independently reviewed the MR angiograms after masking the lesions and the corresponding contralateral sites. The readers were asked to determine whether vascularity was higher on the right side, higher on the left side, or equal on both sides. The results were analyzed by the Kappa statistic and Pearson's chi-square test. The blood vessels of the breasts were clearly seen in all cases. There was good agreement among the observers (kappa > 0.54 ) in assessing vascularity on both sides. Breasts harboring malignant neoplasms were found to have a higher vascularity than the contralateral breasts (p < 0.005). This sign of malignancy had a sensitivity of 76.5 %, a specificity of 57 %, and an accuracy of 72.6 %. Blood vessels of the breast can be depicted by MR angiography. Unilateral malignant neoplasms are associated with a higher ipsilateral vascularity. In conjunction with other indications of malignancy on gadolinium-enhanced MR images, a higher ipsilateral vascularity may serve as an additional sign of malignancy. Received: 4 April 2000 Revised: 14 August 2000 Accepted: 18 August 2000     

Isolation and culture of different epidermal and dermal cell types from human scalp suitable for the development of a therapeutical cell spray

BACKGROUND: Previous studies demonstrated, that cultured epithelial autografts (CEA) can be isolated and skin cell sprays can be produced for application on different types of wounds. The purpose of the present study was to determine which cell types can be isolated from the human scalp and whether these cells can be used for spray transplantation. METHODS: Outer root sheath cells (ORS), keratinocytes, melanocytes, dermal papilla cells (DP), and dermal sheath cells (DSC) were isolated from human scalp tissue. Isolated cells were characterized, expanded and sprayed in an in vitro model. Growth behaviour, morphology and cell counts were compared with non-sprayed cells. RESULTS: With acceptable time, equipment and laboratory personnel a sufficient amount of keratinocytes, ORS, melanocytes, DP cells and DSC cells could be achieved. The cells are sufficient for application as a cell spray. Cells, positive for Integrin alpha6, Cytokeratin 19, CD73 and CD105 were identified within the cultures. CONCLUSIONS: Human scalp is suitable to gain epidermal and dermal cells for the development of therapeutic cell spray transplantation. Further studies have to determine, whether these cells can be combined to produce wound specific skin substitutes.     

Atypical presentation of distal renal tubular acidosis in two siblings

Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy.     

Influence of donor MHC class I antigen expression on graft survival after rat parathyroid allotransplantation

BACKGROUND AND AIMS: We investigated the influence of donor MHC antigen expression on graft survival after parathyroid transplantation in three different strain combinations. METHODS: MHC class I and II expression on parathyroid tissue of Lewis (LEW), Dark Agouti (DA), and Wistar-Furth (WF) rats was first analysed semiquantitatively by immunohistochemistry. Additionally, five groups were transplanted: (1) LEW to LEW, (2) DA to DA, (3) LEW to DA, (4) WF to LEW, and (5) DA to LEW. METHODS: MHC class I expression was strong in DA, moderate in WF, and weak in LEW rats; MHC class II expression was negative in all three strains. In the interstitium of all investigated tissue specimens, the proportion of MHC class II-expressing cells was low. RESULTS: After syngeneic transplantation, graft survival could be documented over the whole observation period. A mean graft survival of 20 (+/-2) days was observed following transplantation from LEW to DA, grafts in the group WF to LEW were rejected after 13 (+/-1) days, and graft function lasted 8 (+/-2) days in the group DA to LEW. The number of intragraft leukocytes expressing MHC class II molecules was equal in all groups, whereas increased levels of MHC class I on rat parathyroid tissue before transplantation resulted in a more rapid rejection. CONCLUSION: These results demonstrate that immunogenicity of rat parathyroid tissue seems to be determined by the amount of MHC class I expressed on donor parenchymal cells.