Thrombotic microangiopathy induced by long-term interferon-β therapy for multiple sclerosis: a case report

We report the case of a 53-year-old woman treated for 8 years with Betaferon? (interferon-β-1b), who developed mild renal failure with hypertension, proteinuria and glomerular hematuria. Kidney biopsy was consistent with thrombotic microangiopathy (TMA). Considering the strong evidence of interferon-α causing TMA and the numerous immunomodulatory activities shared by INF-α and -β, we incriminated Betaferon as the etiological agent of TMA in our patient. To our knowledge, it is the first time such an association has been published.     

Assessment of the “Skin Reservoir” of Urea by Confocal Raman Microspectroscopy and Reverse Iontophoresis <Emphasis Type="BoldItalic">in vivo</Emphasis>

Purpose To demonstrate the “skin reservoir” of urea by confocal Raman microspectroscopy in vivo and to evaluate its impact on the non-invasive monitoring of the analyte by reverse iontophoresis. Methods Urea was extracted iontophoretically over a 2-h period across the skin of adult volunteers and patients with chronic kidney disease. Confocal Raman microspectroscopic profiles of skin were recorded before and after 30 min of current application. Results Urea extraction was higher at the beginning of current passage, but then decreased to achieve stable values after 2 h of iontophoresis. After 30 min of iontophoresis, the Raman spectra highlighted a clear depletion of urea at the surface of the skin. Lactate distribution was also modified both at the surface and deeper into the skin. Conclusions A source of urea in the skin, unrelated to the concentration circulating in the blood, was strongly suggested by extracted urea flux observed over time and by the Raman spectroscopy. This “urea reservoir” must be removed before systemic urea levels can be non-invasively monitored by reverse iontophoresis.     

Transplantation of cultured explants of human endometrium into nude mice

The objective of this study was to analyse the histological and immunohistochemical characteristics of cultured explants of human endometrium transplanted into nude mice. Biopsies of eutopic endometrium were taken from six patients during laparoscopic surgery and classified according to the phase of the cycle. All the explants were cultured with oestrogen and progesterone for 24 h before transplantation into 15 mice. Four mice were grafted with explants of menstrual endometrium, four with explants of late proliferative endometrium, and seven with explants of late secretory-premenstrual endometrium. Typical endometrial glands and stroma were observed in 87% of cases 3 weeks after the transplantation. All the grafts revealed histological characteristics of the proliferative phase, even when the endometrial biopsy was taken during the late secretory phase. Immunohistochemical studies revealed that the proliferation index was high, whatever the menstrual phase of the endometrial biopsy. An extensive vascular network developed at the interface between the graft and the surrounding tissue. Vascular endothelial growth factor (VEGF) positive stained cells were observed in all grafts, the VEGF score being significantly higher in epithelial cells than in stromal cells. In conclusion, human endometrial explants, cultured for 24 h, could be successfully transplanted into nude mice. Immunohistochemical studies proved that human cultured endometrial tissue could not only survive in nude mice but could also become very active and develop characteristics different from the tissue of origin. An active vascular network is a necessary condition for the survival of the graft and may be explained by the high VEGF content.     

Serum Fetuin-A Levels Are Associated with Vascular Calcifications and Predict Cardiovascular Events in Renal Transplant Recipients

Summary

Background and objectives

Vascular calcifications predict cardiovascular disease, the major cause of death in renal transplant recipients (RTRs). We studied the determinants of fetuin-A, a potent circulating calcification inhibitor encoded by the AHSG gene, and tested its association with vascular calcifications and long-term survival and cardiovascular events (CVEs) in RTRs.

Design, setting, participants, & measurements

Two hundred seventy-seven prevalent RTRs from a single center were included. CVEs and deaths were prospectively recorded during a 5-year follow-up.

Results

Independent determinants of lower serum fetuin-A levels were lower plasma cholesterol, the AHSG rs4918 G allele, and history of smoking. Low serum fetuin-A level was a determinant of aortic calcifications (assessed using spiral CT). Low fetuin-A levels (≤0.47 g/L, first quintile) were independently associated with CVEs and deaths (hazard ratio = 1.83; 95% confidence interval, 1.07 to 3.04). The association was confirmed for all-cause mortality, and the major adverse cardiovascular endpoints were analyzed separately. Patients with low fetuin-A and high high-sensitivity C-reactive protein (>4.36 mg/L, fourth quintile) levels had a 3.5-fold increased risk of all-cause mortality and CVEs. In the presence of inflammation, CVE-free survival was influenced by common variants in the AHSG gene.

Conclusions

These data show that low fetuin-A levels are independently associated with aortic calcifications and a higher risk of CVEs and mortality. They support fetuin-A as a circulating biomarker able to identify RTRs at risk for vascular calcifications and CVEs.     

Pleth variability index combined with passive leg raising-induced pulse pressure variation to detect hypovolemia in spontaneously breathing patients

The combination of Pleth Variability Index (PVI) and passive leg raising (PLR)-induced pulse pressure variation may help to diagnose hypovolemia in spontaneously breathing patients. In 44 subjects, PVI and Pulse Pressure (PP) variation after PLR were measured before and after induced hypovolemia (blood gift or hemodialysis session). PVI values were significantly greater after hemodialysis session or blood gift (22% vs 18%, P = 0.03); in contrast PP variation did not change significantly (7% vs 4%, P = 0.49). The accuracy of these parameters or of their combination to identify the "after hypovolemia induction" period was weak. In spontaneous ventilation, PVI value is greater after induced hypovolemia, whereas PP variation does not change significantly. The combination of PVI and PLR does not improve the accuracy of the detection of induced hypovolemia.     

Iatrogenic peritoneal adenomyoma after laparoscopic subtotal hysterectomy and uterine morcellation

Five years after laparoscopic subtotal hysterectomy and morcellation, pelvic magnetic resonance imaging demonstrated the presence of an irregular and heterogeneous pelvic mass measuring 40 x 40 x 30 mm. Histologic examination confirmed smooth muscle hyperplasia infiltrated by numerous endometrial glands (adenomyosis).     

Beta 2-microglobulin amyloidosis in a patient treated exclusively by continuous ambulatory peritoneal dialysis

The histological demonstration of beta 2-microglobulin (B2M) amyloidosis in a 75-year-old man treated exclusively by continuous ambulatory peritoneal dialysis (CAPD) for 87 months is reported. Amyloid deposits were detected in all joints from which synovial specimens were obtained at autopsy. It is of note that the patient had never undergone hemodialysis and had suffered only one episode of peritonitis. Both features are of interest, as the few reports of dialysis-related amyloidosis (DRA) in CAPD include patients who have been hemodialyzed and have suffered repeated episodes of peritonitis, both conditions being incriminated in the genesis of B2M amyloidosis. We conclude that DRA may develop in the absence of artificial membranes or frequent peritonitis episodes.