Exploratory Study of the Brain Response in Facial Synkinesis after Bell Palsy with Systematic Review and Meta-analysis of the Literature.

BACKGROUND: Facial synkinesis, characterized by unintentional facial movements paired with intentional movements, is a debilitating sequela of Bell palsy. PURPOSE: Our aim was to determine whether persistent peripheral nerve changes arising from Bell palsy result in persistent altered brain function in motor pathways in synkinesis. DATA SOURCES: A literature search using terms related to facial paralysis, Bell palsy, synkinesis, and fMRI through May 2021 was conducted in MEDLINE and EMBASE. Additionally, an fMRI study examined lip and eyeblink movements in 2 groups: individuals who fully recovered following Bell palsy and individuals who developed synkinesis. STUDY SELECTION: Task-based data of the whole brain that required lip movements in healthy controls were extracted from 7 publications. Three studies contributed similar whole-brain analyses in acute Bell palsy. DATA ANALYSIS: The meta-analysis of fMRI in healthy control and Bell palsy groups determined common clusters of activation within each group using activation likelihood estimates. A separate fMRI study used multivariate general linear modeling to identify changes associated with synkinesis in smiling and blinking tasks. DATA SYNTHESIS: A region of the precentral gyrus contralateral to the paretic side of the face was hypoactive in synkinesis during lip movements compared with controls. This region was centered in a cluster of activation identified in the meta-analysis of the healthy controls but absent from individuals with Bell palsy. LIMITATIONS: The meta-analysis relied on a small set of studies. The small sample of subjects with synkinesis limited the power of the fMRI analysis. CONCLUSIONS: Premotor pathways show persistent functional changes in synkinesis first identifiable in acute Bell palsy.

Microdeletion 22q11.2 syndrome: Does thymus incidental surgical resection affect its immunological profile?

Background: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. Methods: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. Results: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/μL vs 16.1 miL in the non-thymus group (p = 0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. Conclusion: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure

No disponible

Microdeletion 22q11.2 syndrome: Does thymus incidental surgical resection affect its immunological profile?

BACKGROUND: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. METHODS: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. RESULTS: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/µL vs 16.1µL in the non-thymus group (p=0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. CONCLUSION: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure.

Detection of Merkel cell virus and correlation with histologic presence of Merkel cell carcinoma in sentinel lymph nodes.

BACKGROUND: Adjuvant treatment can dramatically improve the survival of patients with metastatic Merkel cell carcinoma (MCC), making early, accurate detection of nodal disease critical. The purpose of this study was to correlate Merkel cell virus (MCV) detection with histopathologic disease in sentinel lymph nodes (SLNs) of MCC. METHODS: Merkel cell carcinoma cases with SLN (n=25) were compared with negative controls (n=27). Viral load was obtained by quantitative polymerase chain reaction (PCR) for regions VP1 and LT3 of MCV. Histopathologic disease and viral load were correlated. RESULTS: Merkel cell virus was detected in 16 out of 17 (94%) of primary MCC (mean viral load (MVL)=1.44 copies per genome). Viral load in the negative controls was <0.01 copies per genome. Merkel cell carcinoma was present in 5 out of 25 (20%) SLN by histopathology, and MCV was detected in 11 out of 25 (44%) MCC SLN (MVL=1.68 copies per genome). In all, 15 out of 25 (60%) SLN showed correlation between histologic and MCV results. In all, 2 out of 25 (8%) samples were histopathologically positive and PCR negative. Of note, 8 out of 25 (32%) samples had detectable MCV without microscopic disease. CONCLUSION: Patients with positive SLN for MCV even if negative by histopathology were identified. The application of molecular techniques to detect subhistologic disease in SLN of MCC patients may identify a subset of patients who would benefit from adjuvant nodal treatment.

DNA methylation profiles delineate epigenetic heterogeneity in seminoma and non-seminoma.

BACKGROUND: It remains important to understand the biology and identify biomarkers for less studied cancers like testicular cancer. The purpose of this study was to determine the methylation frequency of several cancer-related genes in different histological types of testicular cancer and normal testis tissues (NT). METHODS: DNA was isolated from 43 seminomas (SEs), 14 non-SEs (NSEs) and 23 NT, and was assayed for promoter methylation status of 15 genes by quantitative methylation-specific PCR. The methylation status was evaluated for an association with cancer, and between SEs and NSEs. RESULTS: We found differential methylation pattern in SEs and NSEs. MGMT, VGF, ER-ß and FKBP4 were predominately methylated in NSEs compared with SEs. APC and hMLH1 are shown to be significantly more methylated in both subtypes in comparison with NT. When combining APC, hMLH1, ER-ß and FKBP4, it is possible to identify 86% of the NSEs, whereas only 7% of the SEs. CONCLUSIONS: Our results indicate that the methylation profile of cancer-associated genes in testicular cancer correlates with histological types and show cancer-specific pattern for certain genes. Further methylation analysis, in a larger cohort is needed to elucidate their role in testicular cancer development and potential for therapy, early detection and disease monitoring.

Admixture estimates for Churuguara, a Venezuelan town in the State of Falcón.

BACKGROUND: The present Venezuelan population is the admixture product of Amerindians, Europeans and Africans, a process which was not homogeneous over the country. Blood groups, STRs and VNTRs, specifically D1S80, have been used successfully in admixture studies, but few have been made in Venezuela. AIM: This study aims to estimate the admixture components of Churuguara, Venezuela, and to evaluate the genetic relationship of this population with other Venezuelan as well as worldwide populations through principal component analysis and the study of dendrograms based on genetic distances. SUBJECTS AND METHODS: Gene frequencies of blood groups ABO and Rh (only anti D), of STRs VWA, F13A01, FES/FPS and VNTR D1S80 were studied in a sample of 60 individuals born in Churuguara, a Venezuelan town of admixed ancestry in the State of Falc6n. Admixture was estimated with Chakraborty's gene identity method, and Nei's standard genetic distance was used to build two dendrograms with the neighbour-joining approach, one based on the three STRs and the other based only on D1S80. Principal component analyses with the gene frequencies of these markers were also performed. RESULTS: The frequency of allele ABO*O was 0.788, of ABO*A was 0.187 and of RH*D was 0.74. D1S80 showed 16 different alleles with a heterozygosity of 0.880, whilst the three STRs showed only eight different alleles and heterozygosities between 0.733 and 0.797. The estimates of admixture obtained in this analysis were 52.5% for the Spanish parental group, 27.6% for the African and 19.9% for the Amerindian. Comparison of Churuguara with other Latin American populations shows that its African component is not as high as that observed in Colombian Choco, but it is higher than that observed in other samples from Colombia, Chile and Maracaibo (Venezuela). CONCLUSIONS: Results of the admixture analysis are consistent with those obtained with two dendrograms and principal component analyses, suggesting that the strong initial Amerindian component of 500 years ago has been diluted by the continuous flow of European genes, mainly Spanish, to this region.

Exercise supplementation to dipyridamole prevents hypotension, improves electrocardiogram sensitivity, and increases heart-to-liver activity ratio on Tc-99m sestamibi imaging.

BACKGROUND: Myocardial perfusion imaging with dipyridamole is an alternative with which to evaluate patients who are unable to exercise. Many patients who undergo dipyridamole testing are limited in their ability, but are not completely unable, to exercise. There are benefits from adding low workload exercise to dipyridamole testing, including a reduction of thallium 201 concentration in the liver, leading to a higher heart-to-liver activity ratio and better image quality. This prospective study was designed to evaluate a protocol of exercise supplementation during dipyridamole technetium 99m sestamibi imaging and to verify whether a higher heart-to-liver activity ratio could be obtained. We also evaluated the potential of this combined protocol to prevent hypotension and induce ischemic changes on the electrocardiogram (ECG). METHODS AND RESULTS: Ninety consecutive patients who were not completely disabled for exercise underwent dipyridamole Tc-99m sestamibi cardiac single photon emission computed tomography with a protocol of exercise supplementation (DipEx). The heart-to-liver activity ratio, hemodynamics, and electrocardiographic changes were studied. The findings were compared with those of a control group (Dip) composed of 99 patients who underwent dipyridamole infusion alone. Patients with left bundle branch block, pacemaker, and atrial fibrillation were excluded. The DipEx patients tolerated the protocol, exercising 4.2 +/- 1.3 minutes on the treadmill (Bruce protocol). Compared with Dip, patients in the DipEx group had a higher heart-to-liver activity ratio (1.3 +/- 0.4 vs 1.6 +/- 0.5, respectively; P =.00001), had no incidence of hypotension (6% vs 0%, respectively; P =.03), and had a higher sensitivity of the ECG to detect ischemia (6% vs 34%, respectively; P =.003). The increase in sensitivity seen in the DipEx group was accompanied by a significant decrease in specificity compared with the Dip group (67% vs 100%, P =.000001). CONCLUSIONS: Our data show that the addition of limited exercise to dipyridamole results in benefits during Tc-99m sestamibi imaging, increasing heart-to-liver activity ratio, preventing vasodilator-induced hypotension, and improving ECG sensitivity for the detection of ischemia. Furthermore, this protocol also provides an estimation of the patient's physical capacity and could be used as an alternative for patients undergoing dipyridamole infusion who are not completely unable to exercise.

[Familial pituitary tumor with somatotropic compromise]. / Tumor hipofisario familiar de compromiso somatomamotrópico.

Pituitary adenoma, familiar type, with apparent affection over the involved somatomammotropin of secretion of growth hormone and prolactin, with dominant autosomic transmission, is described for the first time. It was seen that a couple of members without demonstrable tumour, showed clinical data (phenotype) of acromegaly. On investigation of histocompatibility antigens it was observed that the patients with tumour and other symptomatic ones, but without tumour, shared the same haplotypes, and so is very possible that investigation of HLA antigens in patients with pituitary tumour, contributes to better identify its nature and frequency.

Long-acting bromocriptine for the acute treatment of large macroprolactinomas.

Six patients with hyperprolactinemia, visual impairment and large macroprolactinoma were treated with a long-acting bromocriptine, in dosage of 50 mg as a single im injection. All patients underwent a full assessment of pituitary prolactin (PRL) secretion before treatment and the studies were repeated about every week during 40 days. Following bromocriptine injection a rapid amelioration of the clinical and visual defects occurred in all patients. Likewise, a significant reduction of the hyperprolactinemia was documented in all six patients and in three of them serum PRL levels reached values as low as 20 ng/ml, and a tumor size reduction was demonstrated by cranial computerized tomography in three of the six cases. No side effects were associated with the administration of bromocriptine. From this study we conclude that the long-acting bromocriptine represents an additional option for the initial management of large prolactinomas in particular when they are associated with severe visual impairment.

Bromocriptine therapy as pre-operative adjunct of non-functional pituitary macroadenomas.

Although bromocriptine administration produces reduction in size of prolactinomas, its effect upon non-functional pituitary adenomas is still uncertain. Nine patients with macroadenomas, 2 of them with prolactinomas and 7 with non-functional tumours, received bromocriptine prior to transsphenoidal surgery. Size reduction of tumour mass was assessed by computerized tomography and by visual field examination before and following bromocriptine treatment. There were no signs of size diminution or pathological changes in the non-functional adenomas treated pharmacologically during 15 to 360 days. Both patients with prolactinomas had radiological evidence of size reduction and morphological changes on microscopic examination. These 2 patients had tumours with prolactin granules (immunocytochemistry) and adenoma cells showed reduced cytoplasmatic, nuclear and nucleolar areas. Neither vascular damage, cell necrosis, nor infarction was observed by electron microscopy. Patients with non-functional tumours as determined by immunocytochemistry and hormone production did not benefit from bromocriptine. The suggestion that bromocriptine can be used as primary treatment for non-functional pituitary tumours is not supported by the present study. Conversely, in cases of macroprolactinoma, bromocriptine is a useful pre-operative adjunct when surgery is planned and for those patients in whom a surgical cure is considered difficult owing to the tumour size.