Population and breast cancer patients' analysis reveals the diversity of genomic variation of the BRCA genes in the Mexican population.

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.

Monitoring of circulating antibodies in a renal transplantation population: preliminary results.

BACKGROUND: The presence of circulating antibodies (CA) against human leukocyte antigen (HLA) and major-histocompatibility-complex class I-related chain A (MICA) antigens has been associated with worse renal function and reduced kidney allograft survival. We sought to describe the presence of donor-specific anti-HLA antibodies, non-donor specific antibodies, and antibodies against MICA antigens among a cohort of renal transplant recipients with respect to their evolution effects on renal function and occurrence of an acute rejection episode (AR) after transplantation. METHODS: This prospective study of 22 renal transplant recipients of deceased donor kidneys underwent studies of antibodies before and 3 months after grafting using Luminex technology. RESULTS: Ten patients (five men and five women) showed preexistent CA. Comparing patients with versus without preformed CA, we did not observe a significant difference in donor and recipient age or gender. Eight patients (80%) with CA had undergone induction treatment with anti-human-activated T-lymphocyte rabbit immunoglobulin and 2 (20%) with basiliximab. There were no differences between groups regarding the incidence of acute rejection episodes (ARE n = 3 each). There was one case of Banff grade IIB ARE in a patient without preexisting CA; the other episodes were low-grade cellular responses. There were no differences in other variables including cold ischemia time, HLA mismatches, panel-reactive antibody levels, number of transfusions, cytomegalovirus infection or renal function at discharge and 3 months later. Retransplantation was the only factor associated with preformed CA. Retransplantation and preformed CA were associated with CA at 3 months after transplantation. CONCLUSIONS: CA monitoring is important for highly sensitized renal transplants, although our experience failed to show a difference in graft survival or renal function in the first 3 months' follow-up.

[Aggressive fibromatosis of the head and neck in pediatric age. A case report and review of the literature]. / Fibromatosis agresiva de cabeza y cuello en la edad pediátrica. Un caso clínico y revisión de la literatura.

BACKGROUND: Desmoid tumor is a rare benign mesenchymal neoplasm in children primarily originated in the muscle connective tissue, fascial sheaths, and musculoaponeurotic structures. It is often misdiagnosed as fibroids, reactive processes or low-grade fibrosarcomas. It is characterized by slow growth, locally aggressive nature, high recurrence rate without metastasize capacity. MATERIAL AND METHODS: 7 year old girl with right paramandibular tumor, a year of evolution. It was characterized by slow and painless growth, trismus and mandibular latero-deviation to the left during mouth opening. Imaging tests showed soft parts tumor in masseteric region with a periosteal reaction in the mandibular body. The biopsy reported a desmoid tumor. RESULTS: Risdon approach was performed for tumor resection and external cortical Split mandibular body, without preserving the marginal branch of CP VII. The pathology reports of aggressive fibromatosis without bone involvement. It currently presents marginal paralysis and free-disease. CONCLUSIONS: Desmoid tumors of head and neck are difficult to treat because of the proximity or involvement in vital structures, infiltrative nature and tendency to local recurrence. Primary surgery with negative surgical margins is the treatment of choice. However, in many cases this involves disfiguring surgery. Therefore, in these cases and in those surgical margins affections, the use of chemotherapy/non-cytotoxic drugs can be an alternative. Because they are low incidence tumors prospective multicenter studies are needed to clarify the role of adjuvant treatment in this tumor.

Maxillofacial metastasis of genitourinary origin. A report of 3 cases and review of the literature.

INTRODUCTION: The maxillofacial region can harbour a wide range of primary tumours, as well as secondary tumours spreading from distant sites. Rare, though nevertheless important among the latter are genitourinary tumours, such as clear cell renal carcinoma and cervical cancer. Diagnosis of the maxillofacial metastasis sometimes precedes that of the original site, though in other cases the metastasis may arise many years after treatment of the primary tumour. CASE REPORT: We present three cases of maxillofacial metastasis of genitourinary tumours, two clear cell renal adenocarcinoma and squamous cell carcinoma of the uterine cervix. The patients were referred our hospital service for diagnosis and treatment, after having been initially evaluated for buccodental symptoms. DISCUSSION: The appearance of a maxillofacial tumour, initially with the aspect of a primary tumour, may sometimes be the consequence of haematogenous dissemination from another site, such as these surprising cases originating in the genitourinary area. If disseminated metastatic disease is suspected, an extensive oncological screening should be done to evaluate the best therapeutic option in each patient.

Rituximab and chronic plasmapheresis therapy of nephrotic syndrome in renal transplantation patients with recurrent focal segmental glomerulosclerosis.

Focal segmental golmerulosclerosis (FSGS) recurs in 30% of patients with FSGS who received a first renal transplant and in more than 80% of patients receiving a second transplant after a recurrence. Plasmapheresis (PP) can reduce proteinuria and even induce complete remission of proteinuria. We studied the effects of rituximab therapy associated with chronic PP treatment of nephrotic syndrome among 3 adult renal transplant recipients with recurrent FSGS after a fourth, a second, or a third transplantation, respectively. All of these subjects had displayed recurrences in previous transplants. The 3 patients were treated with PP once a week after recurrence; the first and second patients were treated with PP before transplantation surgery seeking to prevent FSGS recurrence. The patients' follow-up times were 21, 35, and 33 months, respectively, before rituximab therapy. During that time, the patients were treated with 133, 62, and 94 PP sessions, respectively. All of the patients received rituximab (375 mg/m(2)/wk, 4 doses) and 1 PP session before each rituximab dose. We confirmed the effectiveness of rituximab therapy by demonstrating peripheral CD19 cells to be undetectable after therapy. None of the patients treated with rituximab achieved remission of proteinuria. One patient showed proteinuria reduced by 26%, the second by 44%, and the third had no change. None of the patients had infectious complications or graft loss at 1 month follow-up. Our experience with 3 adult renal transplant recipients with recurrent FSGS and chronic PP therapy showed failure of rituximab to achieve remission in nephrotic syndrome.

Ezetimibe in the treatment of uncontrolled hyperlipidemia in kidney transplant patients.

Dyslipidemia is an important complication affecting kidney transplant recipients. Statins, the first-line therapy, are often insufficient. Ezetimibe may be effective in combination with statin therapy. We performed a retrospective study to determine the safety and efficacy of ezetimibe treatment in addition to statin therapy among 27 stable renal transplant patients with uncontrolled hypercholesterolemia. We obtained fasting lipid profiles at 3 and 6 months before ezetimibe therapy, while the patients were receiving statins at maximum tolerated doses. Statin doses were stable during the study. All patients received ezetimibe (10 mg) once daily. Fasting lipid profile, kidney function, liver enzymes, creatine kinase, and immunosuppressive drug levels were obtained at baseline as well as at 3 and 6 months post-ezetimibe initiation. Combination therapy resulted in median reductions in total cholesterol of 29% (interquartile range [IQR] 12-39; P = .0001) and 28% (IQR 9-38; P = .0001); in low-density lipoprotein cholesterol of 34% (IQR 16-61; P = .0001) and 44% (IQR 24-56; P = .0001); and in triglycerides of 14% (IQR 4-31; P = .01) and 19% (IQR 1-37; P = .006) at 3 and 6 months post-ezetimibe therapy, respectively. There were no significant differences in high-density lipoprotein cholesterol, renal function, proteinuria, creatine kinase, amylase, liver function, body mass index, or drug levels. There were no adverse drug reactions that mandated treatment withdrawal. When combined with statin therapy ezetimibe seemed to be a safe and effective treatment for uncontrolled dyslipidemia among renal transplant patients.

[Tansitional vesical cell carcinoma metastatizing to the sphenoid sinus]. / Metástasis esfenoidal de un carcinoma de células trancisionales de la vejiga.

Secundary tumors of the paranasal sinus are very uncommon with only one hundred cases reported in the literature up to 2001. The commonest site of the primary tumor is the kidney. The maxillary sinus is most often involved. The Sphenoid sinus is the rarest site. We report a rare case of metastasis to the sphenoid sinces from a transitional cell bladder tumor in a 69-year-old man who died after treatment with chemotherapy and we also review the liteature.

[Plasma immunoadsorption treatment of malignant multiple sclerosis with severe and prolonged relapses]. / Tratamiento con plasma inmunoadsorción en brotes graves y prolongados de esclerosis múltiple maligna.

INTRODUCTION: The treatment of prolonged, severe relapses in multiple sclerosis (MS) patients who respond poorly to high-dose intravenous corticosteroids is not yet established. Plasma immunoadsortion (IA) removes immunoglobulins (IgG), immune complexes, and complement from plasma. It may bear some advantages compared to plasmapheresis, a nonselective procedure that requires substitution of patient plasma by colloids solutions or plasma, which may carry a potential risk for viral infections. PATIENTS AND METHODS: Three relapsing-remitting MS patients with a malignant course received IA. All they were experiencing a prolonged relapse unresponsive to high-dose intravenous corticosteroids, causing a locked-in state in two of the patients and severe pseudobulbar impairment in the third one. Five to six IA consecutive sessions were administered along a 7-10 days course. RESULTS: IA was followed by a prompt and unequivocal clinical response in all three patients, which paralleled a decrease in IgG, fibrinogen, and C3 complement serum levels. IA administration was followed by immunosuppressor therapy, either with cyclophosphamide and intravenous ACTH (2 cases) or mitoxantrone (1 case). Improvement has been sustained along a mean follow-up of 7.6 years (range: 7-8.5 years), only one of the patients suffering two mild clinical relapses. CONCLUSION: We believe that IA may be useful, either as a coadyuvant or alternative treatment in severe relapses in MS patients that do not respond to high-dose intravenous corticosteroid therapy.

Visceral leishmaniasis (Kala-Azar) in transplant recipients: case report and review.

BACKGROUND: In endemic areas, visceral leishmaniasis has been identified as an opportunistic infection in patients with derangements in their cellular immune system. METHODS: We report a renal transplant patient with visceral leishmaniasis. We also reviewed the previously published cases of 17 organ transplant recipients with this parasitic disease. RESULTS: Visceral leishmaniasis occurred a median time of 8 months after transplantation, and the clinical picture was characterized by fever, splenomegaly, and blood cytopenias. Leishmaniae were detected in bone marrow in 16 of 18 patients and diagnostic serology results were found in 8 of 10 tested patients. Pentavalent antimonials were used to treat 16 patients, five of which developed pancreatitis. Five of 18 patients died, including two untreated patients. Relapses of visceral leishmaniasis occurred in 4 of 13 survivors. CONCLUSIONS: In endemic areas, visceral leishmaniasis may complicate the clinical course of organ transplantation and can have fatal consequences, particularly when untreated.

[Membranous nephritis after renal transplantation]. / Nefropatía membranosa después del trasplante renal.

8 cases of membranous glomerulonephritis (MG) after renal transplants (RT) are presented; one being a recurrence of the original disease and the other 7 due to a different cause of renal insufficiency. The total incidence of MG after transplantation was 1.63%; 1.39% being the incidence of MG of new cases. Only 1 patient showed decrease of renal function and in this case the MG was accompanied by chronic rejection lesions. There was no sign of neoplasias nor drugs producing MG. As far as chronic infections are concerned, only one patient showed B antigen and it was not observed during the immunofluorescent test in the biopsy. 6 patients had urological complications after the renal transplant (3 cases of urinary fistula; 2 cases of obstructive uropathy; 1 case of short ureter). 2 patients experienced the start of hemodialysis due to focal and segmentary glomerulosclerosis. The beginning of proteinuria commences between 2 and 23 months after the RT (median 13,0 +/- 7,5 moths); with a range of between 2.0 and 12.0 gr/day (median: 6.8 +/- 3,2 Z gr/day), this being nephrotic in 4 cases. Proteinuria improved 1 case, and persisted in the other patients at the same level registered previous to the diagnosis. MG is a non-frequent complication or RT and is usually benign. Patients with post-transplant urologic complications could be considered to have a higher risk of developing a MG "de novo".