A novel splice-site mutation in the AAGAB gene segregates with hereditary punctate palmoplantar keratoderma and congenital dysplasia of the hip in a large family.

BACKGROUND: Palmoplantar keratoderma punctata (PPKP) is a heterogeneous group of disorders characterized by hyperkeratotic papules occurring over the palms and soles during adolescence. PPKP type 1, also known as PPKP Buschke-Fischer-Brauer type, was recently found to result from mutations in the AAGAB gene, encoding the p34 protein. PPKP type 1 is usually not associated with extracutaneous features. AIM: To investigate a large family in which PPKP1 was present in association with congenital dysplasia of the hip (CDH). METHODS: A combination of direct sequencing of candidate genes and reverse-transcription PCR was used to identify the molecular basis underlying the clinical features displayed by the patients. RESULTS: Direct sequencing showed a novel intronic mutation in AAGAB, which was found to cosegregate with PPKP and CDH throughout the family. The mutation was found to result in aberrant RNA splicing, leading to exon 4 skipping. CONCLUSIONS: This observation suggests either the existence of a CDH-associated gene in the vicinity of AAGAB, or a hitherto unrecognized role for p34 during skeletal development.

Anthropometry of fetal vasculature in the chorionic plate.

Normal fetal development is dependent on adequate placental blood perfusion. The functional role of the placenta takes place mainly in the capillary system; however, ultrasound imaging of fetal blood flow is commonly performed on the umbilical artery, or on its first branches over the chorionic plate. The objective of this study was to evaluate the structural organization of the feto-placental vasculature of the chorionic plate. Casting of the placental vasculature was performed on 15 full-term placentas using a dental polymer mixed with colored ink. Observations of the cast models revealed that the branching architecture of the chorionic vessel is a combination of dichotomous and monopodial patterns, where the first two to three generations are always of a dichotomous nature. Analysis of the daughter-to-mother diameter ratios in the chorionic vessels provided a maximum in the range of 0.6-0.8 for the dichotomous branches, whereas in monopodial branches it was in the range of 0.1-0.3. Similar to previous studies, this study reveals that the vasculature architecture is mostly monopodial for the marginal cord insertion and mostly dichotomous for the central insertion. The more marginal the umbilical cord insertion is on the chorionic plate, the more monopodial branching patterns are created to compensate the dichotomous pattern deficiency to perfuse peripheral placental territories.

Feto-feto-fetal transfusion syndrome in monozygotic monochorionic triamniotic triplets: vascular evaluation by a cast model.

A unique cast model of the placenta in a rare case of feto-feto-fetal triplet transfusion syndrome (FFFTTS) allowed the demonstration of why the transfusion syndrome developed in one fetus and not in the other two in that single placenta. The vasculature anatomy of a monochorionic triamniotic triplet placenta with FFFTTS of three healthy infants (one donor, two recipients) born in the 35th week of gestation was cast by means of dental casting materials. After the cast hardened, the tissue was corroded, revealing the cast blood vessels. The diameters and lengths of the chorionic blood and intraplacental vessels of the cast placenta were measured with a digital caliper. The cast revealed two artery-artery (A-A) anastomoses on the chorionic plate between the two recipients and the donor. Seven artery-vein (A-V) deep anastomoses connected only the arteries of the donor and the veins of the two recipients. The blood vessel connections among the fetuses allowed the evaluation of a pathologic case with its own control in a single placenta. From the vascular appearance, we speculate that the A-A anastomoses between the two fetuses protected them from developing blood transfusions, but that the A-V anastomoses contributed to their development.

The mechanism of hydrosalpinx in embryo implantation.

BACKGROUND: Hydrosalpinx adversely affects embryo implantation and contributes to poor implantation rates post embryo transfer. Embryo transport depends on concomitant intrauterine fluid motion induced by uterine wall motility, the result of spontaneous myometrial contractions towards the fundus. METHODS AND RESULTS: The uterine dynamics of five patients with hydrosalpinx were recorded and analysed by image-processing techniques: the frequency was higher while the amplitudes and passive widths were lower compared with healthy volunteers. The existing peristaltic activity should have induced intrauterine fluid flow; however, the recordings failed to show the expected transport of fluid bolus. This observation was supported by mathematical simulations based on the hypothesis that fluid accumulation in the Fallopian tube of a patient with hydrosalpinx increases tubal pressure and thereby induces a pressure gradient between the fundus and the cervix. This pressure gradient acts adversely to the cervix-to-fundus intrauterine peristalsis and generates reflux currents that may thrust embryos away from the implantation site. CONCLUSIONS: The reflux phenomenon could explain the reduced implantation rate associated with hydrosalpinx. Resolution of the issue of whether the removal of a Fallopian tube with hydrosalpinx should be undertaken for improving IVF pregnancy rates should be accompanied by prospective randomized clinical trials.

Vascularity index distribution within the testis: a technique for guiding testicular sperm extraction.

Azoospermia is defined as the absence of spermatozoa in the ejaculate, although some foci of spermatogenesis may exist in the testes of these men. Currently, there are no clinical, seminal or hormonal parameters for identifying spermatogenesis within the testis sufficient for achieving genetic offspring. As a result, multiple biopsies are performed at several arbitrary sites of both testes in search of spermatozoa. We developed a power Doppler (PD) ultrasound (US) image-based technique that predicts sites with the greatest potential for spermatogenesis. PDUS images of the testes of azoospermic men were acquired at seven cross-sections to reconstruct a 3-D matrix for constructing a spatial map of preferential regions where spermatozoa are most likely to exist. This technique may obviate the need for arbitrary multiple biopsies that inflict some degree of damage upon testicular tissue, and may increase the success rate of identifying viable spermatozoa in testicular biopsies.

Peristaltic flow in a tapered channel: application to embryo transport within the uterine cavity.

Cyclic uterine peristalsis plays a central role in assisting the transport of sperm to the fallopian tube and later in the conception process in transporting the embryo to a fundal site for implantation. Fulfillment of these essential events within the time limits of fertilization and implantation depends on concomitant intrauterine fluid motion induced by uterine wall motility. A model of wall-induced fluid flow within a finite tapered two-dimensional channel was developed to simulate intrauterine fluid flow pattern and transport phenomena due to symmetric and asymmetric wall displacements. The analysis showed that the transport phenomena are strongly dependent on the phase shift of wall displacement and the angle between the walls. The velocities, flow rates, pressure and the axial transport of massless particles are reduced to zero when contractions are completely out of phase. Cases of reflux and trapping in a tapered channel are discussed for the first time. The reflux phenomenon is most likely to occur when wall motility is asymmetric, especially when the angle between the walls increases, while trapping is enhanced as the asymmetric motility and the angle between the channel walls decrease. The relevance of the results to intrauterine fluid transport phenomena, embryo transfer and hydrosalpinx was explored.

Characteristics of uterine peristalsis in spontaneous and induced cycles.

OBJECTIVE: To characterize the dynamics of the intrauterine fluid-wall interface (IUFWI) from in vivo transvaginal ultrasound images by new techniques of image processing of sagittal cross-sections of the uterus, in healthy women with normal cycles and patients treated with clomiphen citrate (CC). DESIGN: Clinical study. SETTING: An ultrasound unit in a large university-affiliated municipal hospital. PATIENT(S): Twenty-five patients with normal spontaneous cycles (group A) and nine patients treated by CC (group B). INTERVENTION(S): Transvaginal ultrasound examinations. MAIN OUTCOME MEASURE(S): Transvaginal ultrasound images were processed to carry out a computational analysis of the resultant IUFWI. RESULT(S): The amplitude and the width of the IUFWI were higher in group B, but the ratio of these measurements was similar in both groups. The frequency of wall motility of group A was lower and its pattern was more symmetrical than that of group B. CONCLUSION(S): The differences in the dynamic characteristics of spontaneous and CC-induced cycles may constitute an additional parameter that should be considered in embryo transport.

Fiber-optic evanescent-wave spectroscopy and neural networks: application to chemical blood analysis.

An infrared spectral analysis of human blood serum has been carried out with Fourier transform infrared fiber-optic evanescent-wave spectroscopy. The measured spectra were analyzed by neural network analysis to predict concentrations of cholesterol, creatinine, total protein, urea, and uric acid. The predicted concentrations were compared with results from standard chemical analysis of blood and a good correlation was observed.

Dynamics of the intrauterine fluid-wall interface.

Intrauterine fluid movements, which are responsible for embryo transport to a successful implantation site at the fundus, may be induced by myometrial contractions. Myometrial contractions in nonpregnant uteri were studied from in vivo measurements of intrauterine pressures with fluid-filled catheters and by visual observations of high-speed replaying of ultrasound images of the uterus. Transvaginal ultrasound (TVUS) images of sagittal cross sections of the nonpregnant uterus were scanned with an intravaginal ultrasound probe. Images at consecutive times (2 s apart) were digitized and processed by employing modern techniques of image processing. The sets of images were compared to evaluate time variation of the fluid-wall interface with respect to amplitude, frequencies, and wavelength of myometrial contractions. Analysis of TVUS images from 11 volunteers during the proliferative phase revealed that myometrial contractions are fairly symmetric and are propagated from the cervix towards the fundus at a frequency of about 0.01-0.09 Hz. The wavelength, amplitude, and velocity of the fluid-wall interface during a typical contractile wave were found to be 10-30 mm, 0.05-0.2 mm, and 0.5-1.9 mm/s, respectively. Additional data acquisition from a large number of normal subjects is needed to build a data base to predict normal characteristics of myometrial contractions in a nonpregnant uterus, in order to better understand their role in the preimplantation process.

Analysis of intra-uterine fluid motion induced by uterine contractions.

Evaluation of the fluid flow pattern in a non-pregnant uterus is important for understanding embryo transport in the uterus. Fertilization occurs in the fallopian tube and the embryo (fertilized ovum) enters the uterine cavity within 3 days of ovulation. In the uterus, the embryo is conveyed by the uterine fluid for another 3 to 4 days to a successful implantation site at the upper part of the uterus. Fluid movements within the uterus may be induced by several mechanisms, but they seem to be dominated by myometrial contractions. Intra-uterine fluid transport in a sagittal cross-section of the uterus was simulated by a model of wall-induced fluid motion within a two-dimensional channel. The time-dependent fluid pattern was studied by employing the lubrication theory. A comprehensive analysis of peristaltic transport resulting from symmetric and asymmetric contractions is presented for various displacement waves on the channel walls. The results provide information on the flow field and possible trajectories by which an embryo may be transported before implantation at the uterine wall.

Screening for glaucoma with stereo disc photography.

PURPOSE: To determine the value of taking simultaneous stereo photographs of the optic nerve head as a basis for identification of patients with glaucoma. METHODS: Two hundred fifty-eight patients received complete ophthalmological examinations and were ranked on a scale of 1-5 regarding the likelihood of their having glaucoma. Each eye was also photographed using the NIDEK camera, providing stereo pairs of the optic nerve head. The same patients were reclassified by two independent masked observers on the same scale of 1-5, based solely on examination of the photographs. RESULTS: Examination of stereo photographs alone provided maximum sensitivity of 75% and specificity of 95% in identification of glaucoma patients when photographic readings were compared with all available clinical information. CONCLUSIONS: Stereo photographs of the optic nerve head can be used for glaucoma detection with an accuracy that is significantly greater than simple tonometry and with a sensitivity that is equivalent to screening with computerized perimetry.