Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients.

Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995-2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in cases of limb pain before the occurrence of more severe complications.

Detection of HPV by in situ hybridization in thin-layer (ThinPrep) cervicovaginal samples.

We have studied an automated in situ hybridization (ISH) method as a possible alternative approach for detecting high-risk human papillomavirus (HPV) in monolayer (ThinPrep) cervico-vaginal samples, comparing the results with those obtained by polymerase chain reaction (PCR) using consensus primers and studying the relationship between the ISH staining pattern and the viral integration in HPV 16-positive cases. Eighty atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cases were used for our purposes. The patients were monitored through periodic cytologies. ISH with was performed with an automated Ventana System, analysis by PCR was performed with consensus primers and integration of HPV16 was performed by realtime PCR analyzing E2 and E6 genes. Additionally, 27 HSIL cases were also studied to observe the ISH staining patterns. HPV infection was detected by ISH in 21.7% of the ASCUS cases and 55.8% of the LSIL cases. Two distinct staining patterns were observed: multipunctated (MP) and diffuse (DI). In some cases, a mixed pattern (MP + DI) was observed and these cases were considered as MP. The MP pattern increased with the degree of lesion and seemed to have a prognostic value in ASCUS/LSIL cases. The lesion in MP pattern cases persisted throughout the entire study in 77% of cases, whereas in cases with a DI staining pattern, only 41% of them showed persistence of the lesion (p <0.001). No correlation was found between HPV integration and the ISH staining pattern. Given the lower sensitivity and negative predictive value of ISH and its incapacity to demonstrate the integration of high-risk HPV in ASCUS and LSIL cases using liquid-based cytology, we do not recommend this technique for the triage of ASCUS and LSIL cases.

Human papillomavirus detection in urine samples: an alternative screening method.

OBJECTIVES: To investigate the usefulness of human papillomavirus detection in the urine of women with poor gynecologic attention. MATERIALS AND METHODS: Fifty urine and 50 cervical samples from 50 women were analyzed. Polymerase chain reaction was performed on these 100 samples using consensus primers and a low-density microarray-based method for human papillomavirus typing. RESULTS: The concordance of the results between both sample groups was 80%. In the urine samples, the sensitivity of polymerase chain reaction for high-grade squamous intraepithelial lesion was 100%, the specificity was 80%, the positive predictive value was 91%, and the negative predictive value was 100%. CONCLUSIONS: Human papillomavirus detection in urine samples may be used as an alternative screening method for women with poor gynecologic attention.

Modulation of osteoblast activity by serum from diabetic and non-diabetic patients on hemodialysis: a three-dimensional culture study.

BACKGROUND: The aims of our study were to develop a three-dimensional model based on normal human osteoblasts and to determine, with this method, the osteoblastic response to sera of non-diabetic and diabetic patients on hemodialysis for chronic renal failure. METHODS: A protocol for culture of osteoblastic cells in three-dimensional meshworks of bovine type I collagen was developed. The effect on cultures of sera from three groups of patients was studied: 1) 12 diabetic patients on hemodialysis [age: 65 +/- 5.2 years; sex: 6 men, 6 women; duration of dialysis treatment: 21.25 (641) months]; 2) 12 non-diabetic patients on hemodialysis [age: 65.5 +/- 5.4 years; sex: 6 men, 6 women; duration of dialysis treatment: 21.35 (6-40) months]; and 3) 12 healthy volunteer donors (age: 64.2 +/- 4.9 years; 6 men, 6 women). The three-dimensional cultures obtained were processed in the same way as undecalcified bone biopsies, sectioned and stained. A histomorphometrical study was conducted. Parameters calculated were cell number, volume of newly-formed collagen, volume of newly-formed collagen per cell, mineral volume and mineral volume per cell. RESULTS: Number of osteoblastic cells was significantly higher in non-diabetic than in diabetic and control serum-treated cultures. Newly-formed collagen volume was significantly higher in non-diabetic serum-treated cultures than in controls. Deposited mineral volume was significantly lower in diabetic and non-diabetic serum-treated cultures compared to control serum-treated cultures. CONCLUSIONS: The model of three-dimensional culture proposed in the present study is useful in the study of different osteoblast functions including the rate of collagen formation and mineralization.

Primary epidural lymphoma. Case report.

A case of follicular center cell lymphoma arising in the spinal dura mater is presented. To the authors' knowledge, this is the first case of primary epidural lymphoma in which immunohistochemical and molecular investigations demonstrated a follicular center cell origin.