Obstetrical magnetic resonance imaging: maternal anatomy

Eleven patients whose pregnancies were at 34-36 weeks of gestational development underwent magnetic resonance (MR) imaging. Images of the maternal pelvis were assessed for anatomical changes of pregnancy in comparison with MR images of five non-pregnant volunteers. The relationship of the fetal presenting part to the internal os of the cervix was seen in all patients. Effacement of the cervix was identified when present. The maternal spine demonstrated disk abnormalities in nine patients. Changes in venous flow patterns were readily identified in all patients. The inferior vena cava was flattened or obliterated, a high signal was present in the iliac vessels (TE 56), and large collateral vessels were present.     

Genetic variation at a splicing branch point in intron 9 of the low density lipoprotein (LDL)-receptor gene: a rare mutation that disrupts mRNA splicing in a patient with familial hypercholesterolaemia and a common polymorphism

Mutations in the coding sequence, splice junctions or promoter of the gene for the low density lipoprotein (LDL) receptor are known to be the underlying cause of familial hypercholesterolaemia (FH), but mutations of this type cannot be identified in all patients with a clinical diagnosis of FH. We show here that minor sequence changes elsewhere in introns can be deleterious. A minor rearrangement 30 bp upstream from the junction of intron 9 with exon 10 was detected as a heteroduplex in amplified genomic DNA from one out of 300 heterozygous FH patients. The mutation destroys the only consensus sequence for a splicing branch point in intron 9 and analysis of mRNA from cells from the patient showed that it causes retention of intron 9 or, more rarely, in the use of cryptic splice sites in exon 10. The effect of the mutation on mRNA splicing was confirmed by analysis of mRNA in cells transfected with LDL-receptor mini-gene constructs expressing exons 9 and 10, together with the normal or mutant intron 9. A common C/T polymorphism within this branch point in intron 9 of the LDL-receptor gene does not affect mRNA splicing in vitro and is not associated with significant differences in mean plasma cholesterol concentration in a healthy population.      

1141420984Placental exosome suppression of T cell activation and differential target of T cell subsets

Problem: One immunoregulatory pathway that has received little attention is placental exosome release. In normal pregnancy, as factors linked with early immunomodulation decline, placental exosomes become key in modulating T‐cell activation, maintaining the absence of effector T‐cells by enhancing T cell apoptosis and loss of CD3‐z. Method of Study: Placental exosomes were isolated from the maternal peripheral circulation by a chromatographic/MACS procedure developed to specifically purify exosomes of placental origin. Exosomal FasL was identified by immunoelectron microscopy (IEM) and quantified by ELISA. Exosomal suppression of T cell signaling molecules and induction of apoptosis was determined by flow cytometry and DNA fragmentation, respectively. The role of FasL in these events was defined by use of FasL blocking antibody. The differential effect of exosomes on CD3‐z on T subsets was analyzed by western immunoblot (WB). Results: When T cells were co‐incubated with placental exosomes, CD3‐z was down‐regulated, with placental exosomes treated cells expressing 18,900 ± 7,000 MESF units of zeta, while control fraction‐treated cells expressed 49,000 ± 4,800 MESF units of zeta (P < 0.001). This down‐regulation of CD3‐z was partially reversed by pre‐incubating T cells with ZB4 antibody, suggesting a role for FasL. IEM revealed FasL‐antibody complexes located on the exterior of placental exosomes; however, only 20/27 preparations were FasL+. When placental exosomes were added to T cells, the level of CD3‐z expression on CD8⁺ cells was 7.1%, (8.7% vs 59.7%) inhibited 1.43‐fold more than in CD4⁺ cells (85.5 P < 0.01). On CD4⁺CD25⁺ cells, CD3‐z was not significantly inhibited. (P < 0.05). Conclusions: While all term placental exosome preparations tested induced apoptosis, exosomes obtained from 7/27 patients were negative for FasL but were able to induce DNA degradation. These results indicate that, while exosomal FasL is apoptogenic, additional exosome components are capable of inducing apoptosis, but these factors exhibit differential effect on T subsets.     

Whole-body lymphangioscintigraphy: preferred method for initial assessment of the peripheral lymphatic system

In 20 patients with congenital and acquired lymphedema in either upper or lower extremities and in four patients without extremity edema, human serum albumin labeled with technetium-99m was injected intradermally into a digital web space of the hand or foot. With a digital gamma camera that permitted a "sweep" of the torso, serial extremity and whole-body lymphagioscintigraphy (LAS) of the peripheral lymphatic system was performed. In 11 patients with acquired lymphedema, a well-defined obstructive pattern was seen, characterized by discrete peripheral lymphatic trunks, delayed or absent depiction of regional nodes, and delayed but extensive soft-tissue tracer extravasation. Five of nine patients with congenital lymphedema showed hypoplasia characterized by poorly defined lymphatic trunks, delayed depiction of regional nodes, and early and extensive extravasation of tracer. The other four patients showed aplasia, with absence of trunks, no depiction of nodes, and little or no tracer extravasation. LAS is technically simple to perform and requires no special training. Radiation exposure is minuscule, and the procedure is safe and without apparent side effects. For these reasons, whole-body LAS should be the preferred method for the initial assessment of congenital or acquired lymphedema.     

Dermatitis cruris pustulosa et atrophicans revisited: our experience with 37 patients in south India

Background  Dermatitis cruris pustulosa et atrophicans (DCPA) is a distinctive type of chronic superficial folliculitis, with a number of unique features such as its peculiar symmetric localization to legs, extreme chronicity, resistance to therapy, and inevitable alopecia and atrophy.
Methods  All patients with DCPA, attending the Dermatology Outpatient Department at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Hospital, Pondicherry, from December 2006 to June 2008 were included. Parameters recorded were detailed history and examination, hemogram, erythrocyte sedimentation rate, random blood sugar, skin biopsy and cultures from pus and carrier sites (nares, axillae and gluteal fold).
Results  37 patients were studied (35 males and 2 females). Sixteen patients (43.24%) belonged to the 21–30 year-old age group. The disease most commonly began on the legs (81.1%). Majority (78.38%) had a disease duration of less than 5 years. Itching was the most common symptom (89.19%), followed by bleeding and scaling, with no significant systemic symptoms. The lower limbs were involved in all patients. Eleven patients (29.73%) had involvement of other sites – beard, axillae, chest, moustache, abdomen, and eyebrows. Pustules, papules, and scaling were seen in all patients, followed by wiry roughness, atrophy, alopecia, and pigmentation. Aggravating factors included use of full-length synthetic trousers, occupational exposure to potential irritants, and season (summer). Pus culture from the folliculitic lesions grew Staphylococcus aureus in 32 (86.49%) patients. Twenty one patients (56.75%) were carriers of S. aureus in one or more sites.
Conclusion  DCPA is a chronic folliculitis of the legs, with a multifactorial etiopathogenesis, in which staphylococcal carrier status may be a new potential pathogenetic factor.     

Student and intern awareness of ionising radiation exposure from common diagnostic imaging procedures

This study aims to evaluate medical student and intern awareness of ionising radiation exposure from common diagnostic imaging procedures and to suggest how education could be improved. Fourth to sixth year medical students enrolled at a Western Australian university and interns from three teaching hospitals in Perth were recruited. Participants were asked to complete a questionnaire consisting of 26 questions on their background, knowledge of ionising radiation doses and learning preferences for future teaching on this subject. A total of 331 completed questionnaires were received (95.9%). Of the 17 questions assessing knowledge of ionising radiation, a mean score of 6.0 was obtained by respondents (95% CI 5.8–6.2). Up to 54.8% of respondents underestimated the radiation dose from commonly requested radiological procedures. Respondents (11.3 and 25.5%) incorrectly believed that ultrasound and MRI emit ionising radiation, respectively. Of the four subgroups of respondents, the intern doctor subgroup performed significantly better (mean score 6.9, P < 0.0001, 95% CI 6.5–7.3) than each of the three medical student subgroups. When asked for the preferred method of teaching for future radiation awareness, a combination of lectures, tutorials and workshops was preferred. This study has clearly shown that awareness of ionising radiation from diagnostic imaging is lacking among senior medical students and interns. The results highlight the need for improved education to minimise unnecessary exposure of patients and the community to radiation. Further studies are required to determine the most effective form of education.