Practices and ethical concerns regarding preimplantation diagnosis. Who regulates preimplantation genetic diagnosis in Brazil?

Preimplantation genetic diagnosis (PGD) was originally developed to diagnose embryo-related genetic abnormalities for couples who present a high risk of a specific inherited disorder. Because this technology involves embryo selection, the medical, bioethical, and legal implications of the technique have been debated, particularly when it is used to select features that are not related to serious diseases. Although several initiatives have attempted to achieve regulatory harmonization, the diversity of healthcare services available and the presence of cultural differences have hampered attempts to achieve this goal. Thus, in different countries, the provision of PGD and regulatory frameworks reflect the perceptions of scientific groups, legislators, and society regarding this technology. In Brazil, several texts have been analyzed by the National Congress to regulate the use of assisted reproduction technologies. Legislative debates, however, are not conclusive, and limited information has been published on how PGD is specifically regulated. The country requires the development of new regulatory standards to ensure adequate access to this technology and to guarantee its safe practice. This study examined official documents published on PGD regulation in Brazil and demonstrated how little direct oversight of PGD currently exists. It provides relevant information to encourage reflection on a particular regulation model in a Brazilian context, and should serve as part of the basis to enable further reform of the clinical practice of PGD in the country.     

Oxyhemoglobin changes in the prefrontal cortex in response to cognitive tasks: a systematic review

Purpose of the study: the aim of this study was to synthesize PFC fNIRS outcomes on the effects of cognitive tasks compared to resting/baseline tasks in healthy adults from studies utilizing a pre/post design.

Material and methods: original research studies were searched from seven databases (MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, PEDro and PubMed). Subsequently, two independent reviewers screened the titles and abstracts followed by full-text reviews to assess the studies' eligibility.

Results: eleven studies met the inclusion criteria and had data abstracted and quality assessed. Methodology varied considerably and yet cognitive tasks resulted in the ΔO₂Hb increasing in 8 of the 11 and ΔHHb decreasing in 8 of 8 studies that reported this outcome. The cognitive tasks from 10 of the 11 studies were classified as “Working Memory” and “Verbal Fluency Tasks”.

Conclusions: although, the data comparison was challenging provided the heterogeneity in methodology, the results across studies were similar.     

Correlation of functional parameters derived by equilibrium radionuclide angiocardiography and left ventricular size in patients with old myocardial infarction

A total of 131 patients with old (over 6 months) myocardial infarction (MI) and 18 normal subjects underwent equilibrium radionuclide angiocardiography at rest (rERNA). The following rERNA parameters were assessed: left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR), regional wall motion and a left ventricular size index. The patients with old MI were divided into four groups (I to IV) according to increasing left ventricular (LV) size, and the behaviour of the numerical parameters (LVEF, PER, PFR) was evaluated in each group. LVEF proved to be the most sensitive numerical parameter of overall LV performance. PFR decreased significantly from group I to group III but not from group III to group IV, suggesting that for extreme degrees of left ventricular enlargement some compensatory mechanism acts to prevent a too large fall in LV compliance. The effects of the site of the previous MI on LV performance were also evaluated. Both LV size and performance were least affected by postero-inferior MI. The LVEF was, however, a better predictor of LV size than the site of the MI.     

Small-cell neuroendocrine carcinoma of the ampullary region. A clinicopathologic, immunohistochemical, and ultrastructural study of three cases.

We report the clinicopathologic, immunohistochemical, and ultrastructural features of three small-cell neuroendocrine carcinomas of the ampullary region of the duodenum. All patients were men; their ages were 51, 62, and 66 years. The therapy consisted of pancreatoduodenectomy. All patients died of the disease; median survival was 10 months from the diagnosis. The histological appearance was identical to pulmonary and extrapulmonary small-cell carcinoma. The neuroendocrine differentiation was demonstrated ultrastructurally by the presence of dense-core granules, and by the positive immunoreaction for neuron-specific enolase and Leu-7 in each case. One case expressed a focal positivity for chromogranin A (PHE-5) and argyrophilic granules. The same case showed the presence of neurofilaments on frozen material. Neurofilament proteins could not be demonstrated in any case in paraffin sections. Neoplastic cells exhibited cytoplasmic immunostaining for cytokeratins (CAM 5.2) in all cases. In one case, a large number of neoplastic cells (60-70%) exhibited nuclear Ki-67 positivity. We postulate that the disease's histogenesis was from epithelial stem cell expressing both epithelial and neuroendocrine characteristics. The clinical behavior of small-cell neuroendocrine carcinomas of the ampullary region appears to be extremely aggressive, with early metastases and fatal outcome.     

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.     

Exclusive radiotherapy in the treatment of carcinoma of the portio cervicis, stage IIB FIGO]

From January 1970 through December 1987, 135 patients with cervical cancer in stage IIB (FIGO criteria) were treated by means of exclusive radiotherapy in the Istituto del Radio of the Brescia University. Thirty cases were treated by exclusive external-beam radiotherapy (RTT), 39 by brachytherapy (CU) plus external-beam radiotherapy, 24 by combined RTT and CU, 41 by RTT + CU + RTT, and 1 case by CU alone. Crude survival at 5 years is 52.4%, and NED survival is 50%. The differences between the values of crude and NED survival by radiotherapy technique were statistically significant (p 0.05), ranging from 69.8% in the RTT + CU group to 35.5% in the RTT alone group. Twenty-four cases (18%) failed to obtain complete remission, and 24 more cases recurred in the pelvis. Sequelae were evaluated by the French-Italian glossary; they were present in 62 cases (46%), but in 12 cases only (9%) they were severe. The incidence of sequelae was highest in the groups of patients treated with the combined techniques (RTT and CU) which allowed best disease control.     

Compression of the sigmoid of gynecological origin]

The authors report a case of extrinsic stenosis of the sigmoid colon due to inflammation of the uterus and adjoining parts. Attention is drawn to the possibility that the radiological images of this condition may be similar to neoplastic diseases.     

Increased external tibial torsion in Osgood-Schlatter disease

We studied the relationship between Osgood-Schlatter disease and torsional abnormalities of the lower limb in 21 boys with this condition and 20 age- and sex-matched controls. 3 groups of knees (20 control knees, 21 symptomatic and 21 asymptomatic or less symptomatic knees) were subjected to clinical, radiographic and CT evaluation. We found no statistically significant differences between patients and controls, as regards femoral anteversion, patellar congruence angle, patellar tilt angle and anterior tibial tuberosity-trochlear groove distance, but the condylomalleolar angle and tibial torsion angle were greater in patients. We found no differences between symptomatic and asymptomatic or less symptomatic knees in any of the parameters. All the symptomatic knees were on the side preferentially involved in jumping and sprinting. This increase in external tibial torsion may play a role as a predisposing mechanical factor in the onset of Osgood-Schlatter disease in male athletes.     

Evaluation of a fully automated assay to measure C-telopeptide of type I collagen in serum.

The measurement of the degradation product of the C-telopeptide of type I collagen in serum (s-betaCTX) has been evaluated in the form of an automated chemiluminometric assay. The between-day coefficients of variation ranged between 2.6 and 6.0% over the concentration range 0.12 to 3.25 microg/l. The s-betaCTX value correlated well with alternative serum C-telopeptide (r = 0.983) and urine deoxypyridinoline (r = 0.729) measurements. A significant inverse correlation was found between the s-betaCTX measurement and creatinine clearance in patients with renal disease.     

A two-stage study on multiple sclerosis susceptibility and chromosome 2q33

We have performed a two-stage study to analyse the association of polymorphism on chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in stage-1 in 134 Finnish MS families and the observed associations were tested in stage-2 in 186 MS families. We did not find previously reported allelic or haplotype associations with CTLA4. We obtained a weak signal of two distinct predisposing genes, one proximal the other distal of CTLA4. The putative proximal gene was associated with the marker rs3977 in families lacking HLA-DR2 (P=0.02 and 0.02) and the other distal gene was associated with D2S1271 in families from a high-risk region in western Finland (P=0.02 and 0.01). Based on the >3 cM distance and the lack of linkage disequilibrium between these loci, we conclude that the two association signals are independent. Our results provide preliminary evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.