CLINICAL FEATURES AND GENETIC ANALYSIS OF SIX PATIENTS WITH WISKOTT-ALDRICH SYNDROME REPORTING TWO NOVEL MUTATIONS: EXPERIENCE OF ERCIYES UNIVERSITY, KAYSERI, TURKEY.

AIM: The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by micro-thrombocytopenia, eczema, and recurrent infections. We aimed to share our experience with six children with WAS, including two patients with two novel mutations. MATERIAL AND METHOD: We present phenotypical and laboratory description of six patients with WAS. The initial clinical presentation, biochemical and radiological features, molecular diagnosis together with long-term follow-up data are provided. RESULTS: The patients showed increased serum levels of IgE; otherwise the serum levels of IgM were decreased. The percentages of CD3+ T cells were decreased or within lower limit. Four patients underwent molecular genetics analysis and Western blot studies; two of them showed unpublished mutations: a hemizygous splice site mutation in intron 8 (c.778-2A>T), and a hemizygous deletion in exon10 of the WASP gene (c.1017delT; p.S339fsX444) were detected. Western blot studies confirmed the reduced WAS protein expression in peripheral mononuclear blood cells in four studied patients. CONCLUSIONS: The major characteristics of patients were thrombocytopenia with decreased mean platelet volume and bleeding. All patients had been previously misdiagnosed as idiopathic thrombocytopenic purpura, demonstrating the importance of a careful differential diagnosis, and intense evaluation.

Early 'Aryans' and their neighbors outside and inside India.

Data from archaeology, linguistics, population genetics, and from early Vedic texts, which deal with religion, mythology and rituals, have to be assembled and closely compared in order to gain a comprehensive picture of the early 'Aryans'. Such interdisciplinary dialogue is necessary in order to establish areas of overlap of data. This paper attempts to indicate a western Central Asian origin of the Indo-Aryan speakers, in the steppe belt near the Urals, from where they moved, via the Inner Asian Mountain belt and Bactria, into India. Their gradual migration entailed acculturation with previous populations, their languages and cultures.

Effect of photoactivation protocol and radiant exposure on monomer conversion and flexural strength of a resin composite after water and ethanol storage.

The use of soft-start photoactivation to reduce shrinkage stress has become widespread in restorative dentistry. However, an increased susceptibility to ethanol degradation of polymers formed by pulse-delay photoactivation was reported. It was hypothesized that reductions in flexural strength after ethanol storage were related not only to low curing rates, but also to the radiant exposure employed. A commercial composite was subjected to different curing protocols (continuous at high irradiance, continuous at low irradiance, and pulse-delay) and radiant exposures (6, 12, and 24 J/cm2). After 48 h, differences in degree of conversion were minimal and no differences in strength were detected among specimens stored in water. Ethanol storage caused significant strength reductions in pulse-delay and low irradiance specimens that received 6 J/cm2. The results suggest that when low irradiances or pulse-delay methods are used, a relatively high radiant exposure is necessary to originate a polymer network structure similar to that obtained by continuous high irradiance photoactivation.

Combined dipyridamole and dobutamine echocardiography in myocardial hibernation: comparison with thallium uptake in patients after percutaneous transluminal coronary revascularization under circulatory support.

OBJECTIVE: To investigate the specificity and sensitivity of the combination of dipyridamole and dobutamine echocardiography for predicting functional recovery in patients with reduced ventricular function after coronary angioplasty. METHODS: Twenty-five patients, mean (SD) age 60.8 (10) years, with previous myocardial infarction (> 3 months), angiographically assessed coronary artery disease, and resting regional dysfunction (left ventricular ejection fraction < 35%) were studied. They underwent rest-redistribution thallium Tl-201 single photon emission computed tomography, and low-dose pharmacologic stress echocardiography with dobutamine (up to 10 microg/kg per minute), ultra low-dose dipyridamole (0.28 mg/kg over 4 minutes), and combined dipyridamole-dobutamine administration. RESULTS: The rate of agreement between Tl-201 and stress echo was 59% for dipyridamole, 62% for dobutamine, and 71% for combined dipyridamole-dobutamine (P <.05 vs dipyridamole and vs dobutamine). Combined dipyridamole-dobutamine showed a higher sensitivity (89%) than Tl-201, dobutamine, or dipyridamole (84%, 78%, and 80%). Specificity was lower for functional recovery prediction with Tl-201 (60%) compared with dobutamine (89%), dipyridamole (90%), and combined dipyridamole-dobutamine (91%). CONCLUSION: Thallium is more sensitive than dipyridamole or dobutamine; the sensitivity gap is filled with combined dipyridamole-dobutamine. Pharmacologic stress echocardiography is more specific than Tl-201 scintigraphy.

The physiologic basis for hypernasality during connected speech in cleft palate patients: a nasendoscopic study.

A characteristic pattern of velopharyngeal movement is associated with hypernasality. Nasendoscopic examination can identify the patterns of movement of the velopharynx during connected speech. The nasendoscopic observations provide a safe, objective way of assessing the anatomic dysfunction that causes hypernasality. These observations provide a clearer rationale for the design and placement of pharyngoplasty surgery. Recognition of distinct dysfunctional patterns opens the door to nonsurgical correction of hypernaslity in selected patients using the nasendoscope and video display.

Changes in aesthetic appearance and intelligibility of speech after partial glossectomy in patients with Down syndrome.

Eight patients with Down syndrome, aged 9 years and 10 months to 25 years and 4 months, underwent partial glossectomy. Preoperative and postoperative videotaped samples of spoken words and connected speech were randomized and rated by two groups of listeners, only one of which knew of the surgery. Aesthetic appearance of speech or visual acceptability of the patient while speaking was judged from visual information only. Judgments of speech intelligibility were made from the auditory portion of the videotapes. Acceptability and intelligibility also were judged together during audiovisual presentation. Statistical analysis revealed that speech was significantly more acceptable aesthetically after surgery. No significant difference was found in speech intelligibility preoperatively and postoperatively. Ratings did not differ significantly depending on whether the rater knew of the surgery. Analysis of results obtained in various presentation modes revealed that the aesthetics of speech did not significantly affect judgment of intelligibility. Conversely, speech acceptability was greater in the presence of higher levels of intelligibility.

Speech intelligibility after partial glossectomy in children with Down's syndrome.

Twenty-three children with Down's syndrome, aged between 3.7 and 17.5 years, underwent partial glossectomy for improvement of cosmetic appearance. Improved speech was also expected. Preoperative and postoperative audiotaped samples of spoken words and connected speech on a standardized articulation test were rated by three lay and three expert listeners on a five-point intelligibility scale. Five subjects were eliminated from both tasks and another four from connected-speech testing because of inability to complete the experimental tasks. Statistical analyses of ratings for words in 18 subjects and connected speech in 14 of them revealed no significant difference in acoustic speech intelligibility preoperatively and postoperatively. The findings suggest that a wedge-excision partial glossectomy in children with Down's syndrome does not result in significant improvement in acoustic speech intelligibility; in some patients, however, there may be an aesthetic improvement during speech.

Development of articulation before delayed hard-palate closure in children with cleft palate: a cross-sectional study.

The development of articulation before surgical closure of the hard palate was compared in 75 preschool children with cleft lip and palate and 40 preschool children born without clefts. The children were aged 2 years to 5 years 11 months. The patients had significantly poorer articulation skills than the controls at each age level. Substitutions were the most frequent error, and they did not decrease with age in the patients. Fistula size and a history of speech therapy were significant factors in the articulation error scores only in 5-year-olds. No advantage in articulation proficiency was found for those who had worn a prosthesis to occlude the hard-palate defect.

Is pharyngoplasty a risk in velocardiofacial syndrome? An assessment of medially displaced carotid arteries.

The association of medially positioned internal carotid arteries and velocardiofacial (Shprintzen) syndrome was first made in 1987. This is also the most common syndrome associated with facial clefting. The potentially dangerous implications in children with this syndrome requiring pharyngoplasty for velopharyngeal incompetence and stigmatized hypernasal speech involve potential damage to these vessels. This three-part study was undertaken to analyze this anatomic variant. First, a group of 25 children with velocardiofacial syndrome, velopharyngeal incompetence, and obvious posterior pharyngeal pulsations seen on nasendoscopy was studied by CT angiography to determine the degree of this abnormal vascular pattern. This technique, together with three-dimensional reconstructions, made it possible to determine the precise location of these abnormally positioned vessels. Second, our routine superiorly based pharyngeal flap was measured by lateral cervical x-ray to show the distal tip of the flap. The variance was minimal and demonstrated the tip of most flaps to be at the disk between the C2 and C3 vertebrae. By correlating this information with the CT angiography, the risk of surgery can be determined on strict anatomic grounds, allowing customized flap design in some unilateral cases. In this series of children, routine superiorly based pharyngoplasty would be safe in 52 percent, while in 28 percent a pharyngeal flap would be safe if custom designed, and in the remaining 20 percent surgery should not be attempted because the risk of damage to the carotid arteries is too great. Third, in a double-blind study, velocardiofacial children with obvious pulsations seen on nasendoscopy were grouped with other children with palatal dysfunction. When only endoral examination was performed by plastic surgeons and plastic surgical residents, no vascular pulsations were ever seen. This indicates another important role of nasendoscopy in the preoperative assessment of children for palatopharyngoplasty.

Abnormal carotid arteries in the velocardiofacial syndrome: a report of three cases.

Internal carotid arteries of unusual size and tortuosity were found before or at the time of pharyngeal flap surgery in three children who had the velocardiofacial syndrome with velopharyngeal insufficiency. In two cases, medial displacement of the arteries prevented surgery, and in the other, hypernasality persisted because only a narrow, asymmetrical flap could be raised. Medial displacement of the internal carotid arteries inhibits surgical treatment of velopharyngeal insufficiency, necessitating treatment with a prosthetic speech device in such children. Since displacement and tortuosity may be associated findings in the velocardiofacial syndrome, the exact location of the internal carotids should be ascertained when pharyngeal flap surgery is planned.

The use of nasopharyngoscopy biofeedback therapy in the correction of inconsistent velopharyngeal closure.

Nasopharyngoscopy was used as a visual feedback tool in a 10-year-old girl who had a repaired bilateral cleft lip and palate and was unable to establish velopharyngeal closure during production of sibilant-fricative sounds. After one session, the patient was able to achieve velopharyngeal closure consistently during speech. Nasopharyngoscopy biofeedback therapy may be a useful tool to help children to achieve consistent velopharyngeal closure during connected discourse.

Velopharyngeal insufficiency due to hypertrophic tonsils. A report of two cases.

Two children in whom idiopathic hypernasality was diagnosed were referred for investigation of velopharyngeal function. Multiview videofluoroscopic assessments showed the tonsils prolapsing posteriorly during speech, preventing the palate from fully approximating the posterior pharyngeal wall. Tonsillectomy was recommended. Postoperative evaluations found that the hypernasal resonance was eliminated in both children.

Velopharyngeal insufficiency after adenoidectomy: an 8-year review.

The characteristics of 137 patients referred to the Speech Clinic at The Hospital for Sick Children, Toronto, Canada during the past 8 years for the investigation of persistent hypernasality after adenoidectomy are reported. Over 30% of the patients had preoperative factors that are thought to increase the risk, such as submucous cleft palate, fluid regurgitation through the nose, a family history of velopharyngeal insufficiency or clefting, or hypernasality. Fifty percent of the patients required pharyngoplasty to correct hypernasality, 37% required speech therapy alone, and 13% improved with no treatment.

Clinical evaluation of an adhesive used as a fissure sealant.

PURPOSE: To compare the retention of a multi-use bonding agent (OptiBond) to a conventional sealant (Delton) used as pit and fissure sealants. MATERIALS AND METHODS: An informed consent was obtained from 38 subjects aged 11-17 yrs. Delton, a self-cured sealant, was applied to 86 teeth, and OptiBond, a dual-cure glass filled adhesive, was applied to 85 teeth, under cotton roll isolation and saliva ejector. Each subject received both sealing materials, randomly assigned to the sides of the mouth. The sealed teeth were followed up to 30 months. Clinical evaluation was performed by two examiners and the retention was classified as failure or success. RESULTS: Statistical analysis based on a stratified Cox proportional hazards regression model indicated that OptiBond had better clinical performance than Delton (P < 0.001).

Bonding systems used for sealing: evaluation of microleakage.

To evaluate multi-use bonding systems as the sole material for sealing pits and fissures, this study compared the performance of three adhesives (OptiBond, All-Bond 2 and Scotchbond MP Plus) with respect to microleakage. Each material was applied to 12 teeth with dry-etched surfaces, and to 12 teeth with contaminated-etched surfaces (1 microliter of human plasma). Each group of 12 sealed teeth was divided into three subgroups, and each of these was subjected either to thermal cycling (4,000 cycles at 5-55 degrees C), to thermal and load cycling (4,000 plus 300,000 cycles) or to no cycling. The teeth were placed in a 50% AgNO3 solution, rinsed, immersed in a developing solution and exposed to a fluorescent light. Subsequently, each of the 72 crowns was sectioned at three different positions, generating 432 cross-sections. The severity of dye penetration on each cross-section was evaluated by two methods. An ANOVA was used to assess the main effects of the three factors (product, surface condition and cycling), as well as for their interactions on the severity of microleakage. The results obtained under both evaluation methods demonstrated that OptiBond had the best performance under either dry or contaminated surfaces, while All-Bond 2 and Scotchbond MP Plus performed similarly, with greater microleakage intensity on contaminated etched enamel compared to OptiBond.

Patterns and location of velopharyngeal valving problems: atypical findings on video nasopharyngoscopy.

Patterns of velopharyngeal (VP) valving and the location of velopharyngeal gaps were investigated in 246 consecutive nasopharyngoscopy studies. The predominant pattern of closure was coronal (68 percent), followed by the circular (23 percent), circular with a Passavant's ridge (5 percent), and sagittal (4 percent) patterns. Gaps were found in 181 patients; in 121 they were considered typical (centrally located), in 28 they were in one of the lateral aspects of the valve, and in 32 they were attributed to the shape of the adenoid tissue or to abnormalities in the anatomy or function of the posterior border of the soft palate. Atypical findings occurred primarily in patients with a coronal pattern of valving. These findings raise further questions about treatment for patients with atypical valving problems.

Comparison of multi-view videofluoroscopy and nasopharyngoscopy in the assessment of velopharyngeal insufficiency.

Ratings and drawings of multi-view videofluoroscopy and nasopharyngoscopic studies of the velopharyngeal valve in 25 subjects with velopharyngeal insufficiency (VPI) were compared. The videofluoroscopic projections assessed were lateral, base, and Towne views. The Towne view was visually compared with flexible fiber optic nasopharyngoscopic studies in the same subjects. The Towne view was found to compare well with nasopharyngoscopic examination, and lateral view alone was found to be inadequate for the description of velopharyngeal movements.

Velopharyngeal insufficiency on videofluoroscopy: comparison of projections.

A prospective study of multiview videofluoroscopy was performed on 50 patients with clinically suspected velopharyngeal insufficiency to determine which views are helpful, so that radiation dosage might be reduced. The lateral view alone was insufficient: In 11 patients, velopharyngeal insufficiency was demonstrated on the basal or Towne view when the lateral view appeared normal. The Towne view demonstrated the velopharyngeal portal better than the basal projection when the adenoids were large. The basal view should be reserved for the few cases in which the Towne and lateral projections give insufficient information.