Augmentation mammaplasty in male-to-female transsexuals

Hormonal therapy and gender-confirming surgery are the treatments of choice in appropriately selected male-to-female transsexuals. Penectomy and vaginoplasty are the paramount surgical requests of the male transsexual, but breast enlargement greatly increases subjective feelings of femininity. There are only limited reports on augmentation mammaplasty in male transsexuals, and hardly any attention has been paid to the differences between the female mammary anatomy and its male counterpart. The basic anatomic and surgical considerations of augmentation mammaplasty for 201 male-to-female transsexuals who were operated on from 1979 to 1997 are reviewed and discussed. They include the differences between male and female anatomy and how to feminize the male chest, the results of hormonal therapy and the proper timing of surgery, the choice of implant size and surgical approach, the results that may be expected after surgery, and the implications of all mentioned on the long-term outcome and follow-up after augmentation mammaplasty. Because the referring doctor may not check on the breasts or may not be trained to examine augmented breasts for pathologic conditions, the mammaplastic surgeon has an obligation to ensure the proper follow-up of these patients.     

Secondary corrections of the vulva in male-to-female transsexuals

From December of 1980 to May of 1998, 390 male-to-female transsexuals underwent vaginoplasty by inversion of the penile skin and a triangular perineoscrotal flap. Although minor modifications were made throughout the years, the basic surgical technique remained the same over this 17.5-year period. In 86 of the 390 patients (22 percent), secondary corrections of the vulva were deemed necessary. A total of 130 corrections were performed in these 86 patients. In the same 17.5-year period, the authors performed 26 secondary corrective procedures in 19 patients in whom the initial vaginoplasty had been done elsewhere. Bilateral Z-plasties were performed 69 times to center the labia in instances when the ventral part of the labia majora remained too far apart. This is not advisable, primarily because it will reduce the vascular supply of the penile skin flap. Introital widening by five-flap advancement was performed in 40 cases in which a dorsal skin fold obstructed the introitis. The use of the triangular perineoscrotal flap favors the vaginal and introital width, but its base should be close to the anal ring to prevent such a skin fold. Secondary construction of the labia minora was performed 27 times, and a skin reduction of the labia majora was performed 20 times. So far, the authors have been unable to develop a satisfactory method for primary construction of the labia minora. Because the appearance of the vulva may charge gradually during the first postoperative year, secondary vulvar corrections should not be performed in that period.     

Strategies for rare-event detection: an approach for automated fetal cell detection in maternal blood.

This article explores the feasibility of the use of automated microscopy and image analysis to detect the presence of rare fetal nucleated red blood cells (NRBCs) circulating in maternal blood. The rationales for enrichment and for automated image analysis for "rare-event" detection are reviewed. We also describe the application of automated image analysis to 42 maternal blood samples, using a protocol consisting of one-step enrichment followed by immunocytochemical staining for fetal hemoglobin (HbF) and FISH for X- and Y-chromosomal sequences. Automated image analysis consisted of multimode microscopy and subsequent visual evaluation of image memories containing the selected objects. The FISH results were compared with the results of conventional karyotyping of the chorionic villi. By use of manual screening, 43% of the slides were found to be positive (>=1 NRBC), with a mean number of 11 NRBCs (range 1-40). By automated microscopy, 52% were positive, with on average 17 NRBCs (range 1-111). There was a good correlation between both manual and automated screening, but the NRBC yield from automated image analysis was found to be superior to that from manual screening (P=.0443), particularly when the NRBC count was >15. Seven (64%) of 11 XY fetuses were correctly diagnosed by FISH analysis of automatically detected cells, and all discrepancies were restricted to the lower cell-count range. We believe that automated microscopy and image analysis reduce the screening workload, are more sensitive than manual evaluation, and can be used to detect rare HbF-containing NRBCs in maternal blood.     

Chorionic villi sampling: cytogenetic and clinical findings in 500 pregnancies.

The cytogenetic findings were analysed in a series of 500 pregnancies in which chorionic villi sampling was performed. In all cases a direct method was used, karyotyping being successful in 481 cases (96.2%). The main indication for sampling was maternal age over 36 (412 cases; 82.4%). Abnormal laboratory findings resulted in 24 terminations of pregnancy (4.8%); in addition five unexpected balanced chromosome rearrangements were detected. Twelve of 15 cytogenetic discrepancies were detected at amniocentesis, two after termination, and one at spontaneous abortion. Complete follow up data were available for the first 250 patients, among whom nine pregnancies (3.6%) ended in spontaneous abortion before the 20th week. There were no false negative findings. Seventy additional chromosome studies were performed because of failure of chorionic villi sampling or equivocal results, or for confirmation. Counselling before chorionic villi sampling should include the possibility that subsequent amniocentesis may be needed should mosaicism or other unexpected abnormalities be found. The success rate and accuracy of karyotyping chorionic villi samples by the direct method are acceptable but distinctly less than those of karyotyping cultured amniotic fluid cells.     

Post-transcriptional regulation of the creatine transporter gene: Functional relevance of alternative splicing

Background

Aberrations in about 10–15% of X-chromosome genes account for intellectual disability (ID); with a prevalence of 1–3% (Gécz et al., 2009 [1]). The SLC6A8 gene, mapped to Xq28, encodes the creatine transporter (CTR1). Mutations in SLC6A8, and the ensuing decrease in brain creatine, lead to co-occurrence of speech/language delay, autism-like behaviors and epilepsy with ID. A splice variant of SLC6A8–SLC6A8C, containing intron 4 and exons 5–13, was identified. Herein, we report the identification of a novel variant — SLC6A8D, and functional relevance of these isoforms.

Methods

Via (quantitative) RT-PCR, uptake assays, and confocal microscopy, we investigated their expression and function vis-à-vis creatine transport.

Results

SLC6A8D is homologous to SLC6A8C except for a deletion of exon 9 (without occurrence of a frame shift). Both contain an open reading frame encoding a truncated protein but otherwise identical to CTR1. Like SLC6A8, both variants are predominantly expressed in tissues with high energy requirement. Our experiments reveal that these truncated isoforms do not transport creatine. However, in SLC6A8 (CTR1)-overexpressing cells, a subsequent infection (transduction) with viral constructs encoding either the SLC6A8C (CTR4) or SLC6A8D (CTR5) isoform resulted in a significant increase in creatine accumulation compared to CTR1 cells re-infected with viral constructs containing the empty vector. Moreover, transient transfection of CTR4 or CTR5 into HEK293 cells resulted in significantly higher creatine uptake.

Conclusions

CTR4 and CTR5 are possible regulators of the creatine transporter since their overexpression results in upregulated CTR1 protein and creatine uptake.

General significance

Provides added insight into the mechanism(s) of creatine transport regulation.     

Studies on cell fusion between Babesia rodhaini-infected mouse erythrocytes and baby hamster kidney cells.

Heterokaryons were formed by fusion of B. rodhaini-infected mouse erythrocytes and baby hamster kidney (BHK) cells, using Sendai virus. The erythrocyte membrane rapidly lysed inside the BHK cell cytoplasm releasing free parasites. There was no evidence that parasite multiplication occurred inside the BHK cells, nor that parasitized BHK cells were infective for mice.Transient erythrocyte homokaryons were observed in some preparations.The approach indicates a possible method for the in vitro cultivation of Babesia.     

Cell fusion, using Sendai virus, to effect inter-species transfer of a cell-associated parasite (Theileria parva)

Baby hamster kidney (BHK) cells were fused with Theileria parva-infecled bovine lymphoid cells, using u.v. light-inactivated Sendai virus. The resultant hamster/bovine heterokaryons were shown to be infected with T. parva. In some cases parasites were detected in cells which apparently contained only BHK nuclei.     

The devastating outcome of massive subcutaneous injection of highly viscous fluids in male-to-female transsexuals

Illicit subcutaneous injections of massive quantities of highly viscous fluids are still performed, often by unqualified persons. Fifteen male-to-female transsexuals consulted the authors regarding their devastating long-term outcomes after the injection of up to 8 liters of alleged silicone or mineral oil to feminize their bodies. After a latency period of up to 17 years, these injections led to complications ranging from scarring and deformity to infections. These patients were treated conservatively for inflammation and infection or surgically by resection of the oil-infested areas. In view of the potential dangers, feminization by the injection of high-viscosity fluids should be soundly condemned.     

Cloning and characterization of the promoter regions from the parent and paralogous creatine transporter genes

Interconversion between phosphocreatine and creatine, catalyzed by creatine kinase is crucial in the supply of ATP to tissues with high energy demand. Creatine's importance has been established by its use as an ergogenic aid in sport, as well as the development of intellectual disability in patients with congenital creatine deficiency. Creatine biosynthesis is complemented by dietary creatine uptake. Intracellular transport of creatine is carried out by a creatine transporter protein (CT1/CRT/CRTR) encoded by the SLC6A8 gene. Most tissues express this gene, with highest levels detected in skeletal muscle and kidney. There are lower levels of the gene detected in colon, brain, heart, testis and prostate. The mechanism(s) by which this regulation occurs is still poorly understood. A duplicated unprocessed pseudogene of SLC6A8–SLC6A10P has been mapped to chromosome 16p11.2 (contains the entire SLC6A8 gene, plus 2293 bp of 5′flanking sequence and its entire 3′UTR). Expression of SLC6A10P has so far only been shown in human testis and brain. It is still unclear as to what is the function of SLC6A10P. In a patient with autism, a chromosomal breakpoint that intersects the 5′flanking region of SLC6A10P was identified; suggesting that SLC6A10P is a non-coding RNA involved in autism. Our aim was to investigate the presence of cis-acting factor(s) that regulate expression of the creatine transporter, as well as to determine if these factors are functionally conserved upstream of the creatine transporter pseudogene.