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.     

Hemodynamic analysis of descending versus ascending aortomyoplasty, and comparison with intra-aortic balloon pump

Objective: Descending and ascending aortomyoplasty are two surgical procedures intended to induce hemodynamic benefits similar to those of the intra-aortic-balloon-pump (IABP). To date, there have been no studies comparing the two surgical techniques. The objective of this study was to compare coronary blood flow augmentation and afterload reduction as produced by descending and ascending aortomyoplasty counterpulsation Methods: Twenty-two mongrel dogs (18–35 kg) underwent IABP application (n=7), descending (n=8), or ascending (n=7) aortomyoplasty. Left anterior descending (LAD) coronary artery blood flow was measured using a Transonic Doppler flow probe. Left ventricular pressure as well as aortic pressures proximal and distal to either the aortomyoplasty site or the IABP position were monitored continuously. Results: Descending aortomyoplasty induced higher elevation in the LAD blood flow during assisted beats (27% from 10.8±4 to 13.8±6 ml/min, P<0.001) than that induced by either ascending aortomyoplasty (19% from 11.7±5 to 14±5 ml/min, P<0.001) or IABP counterpulsation (18% from 8.6±3 to 10.2±4 ml/min, P<0.001). Conversely, while ascending aortomyoplasty reduced the left ventricular end-diastolic pressure by 16% (from 60±18 to 50±22 mmHg, P<0.001), similar to the 16% after load reduction achieved by the IABP counterpulsation, descending aortomyoplasty failed to induce afterload reduction. Conclusions: Descending aortomyoplasty produces higher coronary blood flow augmentation than either ascending aortomyoplasty or IABP. However, afterload reduction comparable to that achieved by IABP was observed only with ascending aortomyoplasty and not with descending aortomyoplasty.     

Skin test results and self-reported symptom severity in allergic rhinitis: the role of psychological factors

BACKGROUND: In allergic conditions, the degree of skin test reactivity does not always correlate with the severity of clinical symptoms. Additional factors may contribute to the reported symptom severity. OBJECTIVES: To investigate the association between the magnitude of the skin prick test (SPT) response and the reported symptom severity in patients with allergic rhinitis and the possible modifying role of psychological factors. METHODS: One hundred four patients with allergic rhinitis and 23 with non-allergic rhinitis, classified according to their SPT response to 19 aeroallergens, were asked to rate the severity of five symptoms and to indicate whether their symptoms intensified on exposure to five common aeroallergens. They also completed a psychological questionnaire. Results Reported symptom severity of allergic rhinitis did not correlate with weal size for any of the aeroallergens tested or with the number of positive responses on SPT. It was not related to patient age, sex, or education. The reported symptoms severity correlated positively (0.29, P < 0.01) with reported symptom intensification on exposure to allergens. Moreover, both outcomes were positively associated with the psychological factors of hypochondriasis (0.20, P < 0.05 and 0.18, P < 0.05, respectively), and somatic awareness (0.24, P < 0.05 and 0.33, P < 0.01, respectively), but not with neuroticism. CONCLUSIONS: The severity of symptoms experienced by patients with allergic rhinitis is apparently not related to the magnitude of SPT response, but rather to psychological factors of hypochondriasis and somatic awareness. Physicians should be aware of the contribution of psychological factors to patient perceptions of the intensity of symptoms and of the intensification of symptoms on their exposure to allergens.     

Lung cancer in Israel, 1962–1982 I. Jews and Arabs

The magnitude and dynamics of lung cancer incidence in Jews and Arabs in Israel between the years 1962 and 1982 were studied. In general, age-standardized incidence rates increased consistently between the years 1962 and 1976 among Jewish (24% increase) and Arab (39%) males, and to a lesser degree among Jewish females (15%). Arab females had the highest (77%) increase. From 1977 to 1982 a general decrease in incidence rates, which was largest among Arab males (19%) and females (15%), was noted. Rates among Jewish males are currently 26% higher than among Arab males, and are 162% higher among Jewish females than in Arab females. Lung cancer rates in both males and females in Istrael (Jews and Arabs) are lower than in most developed countries in the world. Among the possible reasons are differences in the population risk factors profile, availability of health care and the level of diagnosis and ascertainment of cases.     

Familial Sneddon's syndrome

We report the familial occurrence and apparent autosomal dominant inheritance of Sneddon's syndrome with variable clinical expression. The proband, a 40-year-old woman, presented with livedo reticularis and progressive neurological deterioration following a stroke. The diagnosis was confirmed by cerebral angiogram and skin biopsy, both showing the characteristic findings. Two of the patient's sisters were reported to have been similarly affected in the past. Her mother, two additional siblings and five of her seven children exhibited various vasospastic skin phenomena. Familial aggregation of this disorder may be common and a genetic basis may be involved in its pathogenesis.     

Acute appendicitis in the pregnant patient

Acute appendicitis is the most common surgical problem in pregnancy requiring emergent intervention. To establish a contemporary patient profile and formulate an effective management strategy, a retrospective review was conducted of 84 pregnant patients who underwent laparotomy with a preoperative diagnosis of acute appendicitis. Gestational stage at presentation included the first trimester in 27 patients (32%), the second trimester in 37 patients (44%), the third trimester in 13 patients (16%), and the puerperium in 7 patients (8%). Fifty-four patients (64%) had pathologically proven acute appendicitis; the incidence did not vary by trimester. Other intra-abdominal conditions were detected in 15 patients (18%). There were no significant differences between patients with positive and negative laparotomies (or among trimesters) regarding frequency of presenting symptoms and signs or laboratory results. Operation occurred within 24 hours of symptom onset in 19 of 54 (35%) instances of proven acute appendicitis. Perforation occurred in 23 of 54 patients (43%), all of whom had symptoms exceeding 24 hours (p less than 0.0005). Five instances of perinatal death and one case of extreme perinatal morbidity were associated with negative laparotomies; only one of these was attributed to operation itself. No adverse long-term maternal morbidity or mortality occurred. Wound infection developed in seven cases of acute appendicitis (six perforated) and two negative explorations. We conclude that (1) gestational physiologic changes obscure the accurate diagnosis of acute appendicitis; (2) the natural history of acute appendicitis is not affected by trimester of presentation; and (3) adverse sequelae of acute appendicitis are obviated by prompt operative exploration and prevention of appendiceal perforation.     

Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies.

BACKGROUND: Fluorine 18 fluorodeoxyglucose (FDG) uptake may be increased in atherosclerotic plaques in asymptomatic patients. Repeat positron emission tomography (PET)/computed tomography (CT) studies were assessed for changes in patterns of FDG uptake and CT calcifications. METHODS AND RESULTS: Fifty consecutive cancer patients (mean age, 68 +/- 8 years) had repeat PET/CT studies 8 to 26 months apart. PET, CT, and PET/CT images were retrospectively evaluated for vascular wall abnormalities and for interval changes in the thoracic and abdominal aortas, as well as in carotid and iliac arteries, classified as PET+/CT+, PET+/CT-, and PET-/CT+. There were 485 abnormal sites in the first study and 495 in the second. CT calcifications were found in 46 patients (92%) in the first study and in 47 (94%) in the second. Vascular wall FDG uptake was found in both studies in 37 patients (74%). The pattern changed in 57 of 119 PET+ sites (48%) in the second study compared with 15 of 366 PET- sites (4%) (P < .0001). In the second study new PET+ sites were observed in 36 of 111 sites (32%) versus new PET-/CT+ sites in 19 of 384 sites (5%) (P < .0001). CONCLUSIONS: Changes in vascular FDG activity and CT calcifications can be assessed by repeat PET/CT. FDG-avid foci may represent a dynamic process, transient inflammation, whereas CT calcifications may indicate stable atherosclerosis. These preliminary results support the need for further research.     

Separation of rare cell subpopulations with the aid of biotin-labelled ligands

A universal method for selection of surface marker-positive cells is described. The cells, admixed with an excess of surface marker-negative cells, are In-st labelled with a specific biotinylated ligand and then isolated with the aid of monoclonal, anti-biotin coated beads. The method enables selection and isolation of cells with a frequency as low as 10^-4. The ligand can be an antigen (for selection of infrequent antibody-producing cells), an antibody (for selection of surface antigen-positive cells) or other molecules (for selection of specific receptor-positive cells).     

Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.