Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis

Nephrogenic fibrosing dermopathy (NFD) is a recently described cutaneous fibrosing disorder associated with renal dysfunction. It appears similar to scleromyxedema but with some notable exceptions, including the lack of involvement of the face and absence of plasma cells on histology, systemic involvement, and paraproteinemia. Patients can present with thickened or edematous skin with indurated papules and plaques involving the extremities and the trunk. We report the first three cases of NFD after liver transplantation successfully treated with plasmapheresis. Two patients underwent liver transplantation for hepatitis C virus-induced cirrhosis and one for hepatitis B virus-induced cirrhosis. All the patients had encephalopathy, refractory ascites, and malnutrition prior to transplantation. Like those patients with NFD, all three of our patients had renal dysfunction and required hemodialysis before and after transplantation. Two were not dependent on dialysis at the time of diagnosis, however. These patients had excellent liver allograft function, but the other patient had allograft failure secondary to recurrent hepatitis C. Immunosuppression therapy consisted of basiliximab, mycophenolate mofetil, calcineurin inhibitor, and prednisone. The patients developed "woody" skin induration of the distal extremities, erythematous papules, and contractures at 1, 2, and 120 months after transplantation. Skin biopsies resembled NFD. No paraproteinemia was evident. One to three 5-day courses of plasmapheresis resulted in moderate to marked clinical improvement. The improvement of the kidney function in two of our patients did not appear to correlate with that of the skin disorder, because the kidney function was improving at the time the diagnosis of NFD was made. In conclusion, we report the first three cases of NFD after liver transplantation. Plasmapheresis was moderately successful in resolving the skin-indurated papules, severe skin induration, and associated joint contractures. Preliminary studies (unpublished data) show that decreasing plasma levels of transforming growth factor-beta1 after plasmapheresis appear to correlate with the amelioration of this clinical condition.     

Superior long-term results of renal transplantation in children under 5 years of age

Despite improving overall results of pediatric renal transplantation children under 5 years of age remain a high-risk group with poorer outcomes often because of a higher rate of surgical complications. This retrospective report details a 12-year experience at a single center and examines the outcome in this high-risk group of patients. We reviewed the medical records of 21 children under 5 years of age who received renal transplantation at Loma Linda University Medical Center between July 1988 and August 2000. The patients were evaluated regularly by the same pediatric nephrologist throughout the study period at our outpatient clinic. Mean recipient age was 3 +/- 1.2 (range 2-5) years; weight at transplantation was 13.3 +/- 5.4 kg. Ten (48%) patients received living related donor (LRD) kidneys and 11 (52%) received cadaver (CAD) kidneys. Mean donor ages for CAD and LRD were 14.4 +/- 10 years and 26.6 +/- 4.9 years, respectively. The mean cold ischemia time (CAD only) was 23.3 +/- 10.6 hours. Renal dysplasia (n = 8) and obstructive uropathy (n = 5) were the most common primary diagnoses. Maintenance immunosuppression consisted of Azathioprine or mycophenolate mofetil (MMF), cyclosporine or tacrolimus and prednisone. Mean follow-up was 80.1 +/- 51.4 months. Twelve (57%) grafts have a follow-up >5 years. Patient survival was 100 per cent. Overall graft survival at one, 3, 5, and 10 years were 95, 95, 88, and 88 per cent respectively. Graft survival for LRD recipients was 100 per cent. No graft was lost as a result of a technical problem or vascular thrombosis. One graft each was lost because of delayed graft function complicated by severe cytomegalovirus infection and chronic rejection. At one year the mean serum creatinine was 0.6 +/- 0.2 mg/dL with a mean calculated glomerular filtration rate of 93 +/- 32 mL/min. All 17 children who are now of school age are attending school. We conclude that excellent rehabilitation and superior long-term patient and graft survival can be achieved with renal transplantation in children of this age group with the use of good surgical techniques and close follow-up.     

Preventable infant mortality and quality of health care: maternal perception of the child's illness and treatment

This study used a qualitative methodology to analyze the discourse of mothers from Greater Metropolitan Belo Horizonte, Minas Gerais, Brazil, whose infant children had died from what were considered avoidable causes (diarrhea, malnutrition, and pneumonia), seeking to elucidate the factors associated with utilization of health care services. Identification of the illness by the mother was related to perception of specific alterations in the child's state of health. Analysis of the alterations helped identify the principal characteristics ascribed to each alteration and their relationship to the search for treatment. The authors also studied the mother's assessment of treatment received at health care facilities; 43.0% of the cases involved problems related to the structure of health care services or the attending health care professionals. In 46.0% of the cases, mothers associated the child's death with flaws in the health care service. The study group showed a variety of interpretations of illness, often distinct from the corresponding biomedical concepts. The fact that attending health care personnel overlooked or underrated the mother's perception of the illness and the lack of communications between health care personnel and the child's family had an influence on the child's evolution and subsequent death.     

Carpal tunnel syndrome modifies sensory hand cortical somatotopy: a MEG study

The adult somatosensory system has shown reorganizational abilities at cortical and subcortical levels after peripheral nerve lesions. In the present study the effects of carpal tunnel syndrome (CTS) are investigated as reflected on the somatotopy of the primary cortical hand representation. Position and intensity of cortical sources activated by the separate electrical stimulation of median nerve and Digits 1, 3, and 5 of both affected and non-affected hands are evaluated by magnetoencephalographic (MEG) technique. Correlation of MEG results with patient-, physician- and neurophysiological-oriented evaluations of CTS was carried out. Patients showed changes in cortical hand somatotopy in strict relationship to self-referred assessment of symptoms and hand disability in daily activities, including: 1) a more extended representation of the affected hand when paresthesias prevailed; and 2) a more restricted representation due to lateral shift of the little finger was observed when pain symptoms dominated the clinical picture. Contralateral to the side of CTS, the cortical sources activated by Digit 5-stimulation appeared significantly enhanced with respect to contralateral ones from non-affected hand. When comparing the amplitude of peripheral sensory nerve action potentials of median and ulnar nerves to that of cortical responses (i.e., ECD strengths of M20 and M30 components after stimulation of Digits 3 and 5), a significant selective amplification of M30 with respect to M20 and sensory nerve action potential (SNAP) appeared during Digit 3 stimulation compared to that observed for Digit 5. This has been interpreted as a central magnification mechanism in brain responsiveness, possibly revealing a safety factor enabling sensory perception despite the small peripheral signal due to nerve trunk dysfunction. Hum.     

Vascular endothelial growth factor and prognosis in patients with node-negative breast cancer

Vascular endothelial growth factor (VEGF) has emerged as one of the most important angiogenic growth factors from experimental in vitro and in vivo studies. In the present study, we investigated the relationship between VEGF expression and microvessel density (MVD) and defined their prognostic relevance on a series of 242 patients with node-negative breast cancer, using immunohistochemical methods. In parallel, estrogen and progesterone receptors were quantitatively assessed using the dextran-charcoal technique and cell proliferation was evaluated as S-phase cell fraction according to (3)H-thymidine-labeling index (TLI). The percentage of VEGF-expressing cells varied from 0-95% in the different tumors and was unrelated to menopausal status, tumor size or steroid receptor status. Conversely, a significant inverse relation was observed with patient age or tumor cell proliferation, albeit with very poor correlation coefficients. A significant relation was observed between VEGF expression and MVD (r(s) = 0.55, p < 0.001). Clinical outcome analyzed as a function of high and low VEGF expression showed slight differences in terms of both disease-free survival (DFS) and overall survival (OS) that never reached statistical significance. Moreover, the trend was paradoxically in favor of patients with highly VEGF-expressing tumors. Finally, DFS and OS curves, when analyzed as a function of VEGF expression or MVD, were superimposable. In conclusion, our study did not highlight a prognostic relevance of VEGF expression in patients with node-negative breast cancer, as already observed for MVD.     

Catecholamine production and tyrosine hydroxylase expression in peripheral blood mononuclear cells from multiple sclerosis patients: effect of cell stimulation and possible relevance for activation-induced apoptosis

Sympathoadrenergic mechanisms may play a role in multiple sclerosis (MS). We examined catecholamine (CA) levels and production and tyrosine hydroxylase (TH) expression in peripheral blood mononuclear cells (PBMCs) from MS patients, and the correlation between CA production and apoptosis in PBMCs. PBMCs from MS patients had increased norepinephrine (NE) levels. However, phytohaemagglutinin (PHA)-stimulated PBMCs from MS patients with active disease synthesized less dopamine (DA) than cells from both healthy controls and patients with inactive disease. PBMCs from patients with inactive disease showed lower expression of TH. Pharmacological inhibition of TH in cultured PBMCs stimulated with PHA reduced the percentage of apoptotic cells. Since a failure of activation-induced apoptosis in immune cells may be involved in MS, it is suggested that altered CA production by PBMCs may be implicated in such dysregulation.     

Trends in cancer mortality in Switzerland, 1980-2001.

Trends in cancer mortality in Switzerland were analysed over the period 1980-2001, on the basis of the World Health Organization database. Appropriately developed correction factors were utilized for the period before 1995, to allow for spurious trends introduced by the change between the 8th and the 10th revisions of the ICD. Steady declines in cancer mortality were observed, particularly from the mid-1980s onwards. Over the last decade, the fall in overall age-standardized (world standard) cancer mortality was 11.1% in men (from 158.1 in 1990-1991 to 140.6/100,000 in 2000-2001) and 7.6% in women (from 91.6 to 84.7/100,000), and the decline was larger in truncated rates from 35 to 64 years (-18.0 and -9.7%). In men, all major tobacco and alcohol neoplasms have declined until the late 1990s but have levelled off over the last few years, reflecting recent trends in alcohol and tobacco consumption. The fall in male lung cancer mortality was 20% over the last decade (from 42.9 to 34.3/100,000). In contrast, lung cancer mortality in women has steadily increased by 38% between 1981 and 1991 and by 47% between 1991 and 2001, to reach 10.7/100,000 at all ages and 18.3 at age 35 to 64, due to increased prevalence of smoking in subsequent generations of Swiss women. Other sites showing substantial declines include stomach and colorectum in both sexes, (cervix) uteri and breast in women. Likewise, prostate cancer showed modest favourable trends after 1995. Steady declines were observed for leukaemias, Hodgkin's disease and testicular cancer, namely, the neoplasms most influenced by therapeutic improvements, while trends in lymphomas and myeloma showed no clear pattern.     

Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells.

Betulinic acid is a triterpene with selective cytotoxicity against melanoma, neuroectodermal and malignant brain tumor cell lines. In this study the betulinic acid activity was evaluated, in comparison with doxorubicin, on different human neoplastic and non-neoplastic cell lines and on proliferating normal lymphocytes. Growth inhibition was evident in all the neoplastic cell lines independently on p53 status and histotype. Antiproliferative activity of betulinic acid was related to a cytotoxic effect on two p53 wild-type and on one p53 mutant cell lines and to a cytostatic effect on one p53 mutant melanoma clone. At the same concentrations, normal cells were unaffected indicating a selective effect of this agent. A cytotoxic activity of doxorubicin was evident on all the tested systems. In vivo experiments, performed on one of these cell lines, confirmed the antineoplastic activity of this drug. These data support further preclinical studies of betulinic acid not confined to melanoma and neuroectodermal tumors independently of p53 status.     

Intensive, very short-term chemotherapy for advanced Burkitt's lymphoma in children.

PURPOSE: To improve the 63% event-free survival (EFS) achieved before 1986 in Murphy's stage III to IV Burkitt's lymphoma (BL), both chemotherapy and supportive care were intensified. PATIENTS AND METHODS: From May 1987 to February 2001, 60 children, median age 9 years (range, 2.1 to 17 years), with advanced BL were enrolled onto two sequential institutional studies. From 1987 to 1992, 30 patients were stratified according to the absence (regimen IA, n = 19) or presence (regimen IB, n = 11) of bone marrow (BM) or CNS involvement. After 5-week cytoreductive chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX), and intrathecal MTX or cytarabine, HD cytarabine and cisplatin were provided as a 4-day continuous infusion. Regimen IB was intensified by adding etoposide and HD ifosfamide and escalating MTX doses. Since 1992, regardless of BM or CNS status, 30 patients have been placed on regimen II, which is identical to IB but without ifosfamide. The scheduled duration of regimen II was 45 days. RESULTS: EFS and disease-free survival at 5 years are 81% +/- 5% and 87% +/- 5%, respectively, for 59 assessable patients (73% +/- 8% and 85% +/- 7% for regimen IA + IB, 89% +/- 6%, EFS and disease-free survival, for regimen II; median follow-up, 6.7 years; range, 0.6 to 13.5 years). Six patients, two of whom were receiving regimen II, died as a result of initial treatment failure or relapse, and five patients, none receiving regimen II, died as a result of treatment-related complications. CONCLUSION: This 45-day intensive chemotherapy program is the shortest schedule for disseminated BL and overcomes previously recognized risk factors such as BM and CNS infiltration.