Molecular genetic diagnosis of Glanzmann syndrome in Iranian population; reporting novel and recurrent mutations.

BACKGROUND: Glanzmann thrombasthenia (GT) is a rare autosomal recessive abnormality of platelet aggregation with quantitative and/or qualitative abnormality of αIIbß3 integrin. The αIIbß3 is a platelet fibrinogen receptor, which is required for platelet aggregation, firm adhesion, and also spreading. The disease is more prevalent in the populations with a higher rate of consanguineous marriages as in some Middle Eastern populations including Iraq, Jordan, and Iran. Different types of mutations in ITGA2B and ITGB3 genes have been previously reported to cause the disease. RESULT: In this study, 16 patients with the clinical diagnosis of GT were studied. Direct sequencing of the exons and exon-intron boundaries of the above genes revealed mutations in 14 patients (detection rate: 87.5%). Briefly, out of fifteen types of identified mutations, 14 were novel. Seven mutations in the ITGB3 gene included 4 missense [c.2T > C, c.155 G > T, c. 538 G > A, c.1990 G > T], one nonsense mutation [c.1303 G > T], a small deletion [c.1656_1658delCTC] and a deletion of one nucleotide [c.401delA]. Mutations in the ITGA2B were 8 different mutations consisting 2 missense [c.286 T > A, c.842 C > T], 2 deletions [c.1899 del T, c.189-319_236del], an insertion [c.1071_1072insG] and one splice site mutations [c.409-3 C > G], one synonymous mutation that might alter the normal splicing process [c.1392 A > G] and a nonsense mutation [c.1555 C > T]. The causative mutation in 2 patients remained unknown. Using long-range PCR and sequencing, we found a rather large deletion. The break point of this deletion covers 319 nt from the last part of the first intron and 48 nt from the beginning of the second exon of ITGA2B gene. The deletion was also detected in two unrelated patients with the same ethnicity. In addition, in silico analyses of novel mutations were performed. CONCLUSION: There was no recurrent mutation in the studied population. This may be due to either small sample size or the heterogeneity of the studied population.

Development and implementation of a novel panel consisting 20 markers for the detection of genetic causes of male infertility.

Azoospermia factor (AZF) genes are involved in spermatogenesis. Deletions in the region of these genes have been recognised as a major genetic cause of infertility due to defects in spermatogenesis. Klinefelter syndrome (KS) is the other main cause of male infertility. This study was performed to establish a novel method for the detection of genetic causes of infertility in males and also to investigate the prevalence, extent and position of Y chromosome microdeletions in Iranian infertile men. We developed a newly designed panel of fluorescent multiplex-PCR method to amplify 20 markers (15 sequence-tagged sites (STSs) markers which are placed in the Y chromosome AZF region, 2 short tandem repeats (STRs) and 3 segmental duplications (SDs)). This multifunctional method is for the simultaneous detection of Y chromosome microdeletions and KS. Among 149 studied infertile men, one was detected to suffer from KS and seven (4.7%) were detected with the presence of one or more deleted STS loci. The main cause of infertility for the remaining patients would be nongenetic factors. This strategy is represented as a fast and accurate method to determine the frequencies of different AZF microdeletions which are suitable for use in clinical purposes.

Topography of cerebral white-matter disease of prematurity studied prospectively in 1607 very-low-birthweight infants.

The objective of this study was to evaluate to what extent (1) the characteristics of localization, distribution, and size of echodense and echolucent abnormalities enable individuals to be designated as having either periventricular hemorrhagic infarction or periventricular leukomalacia and (2) the characteristics of periventricular hemorrhagic infarction and periventricular leukomalacia are independent occurrences. The population for this study consisted of 1607 infants with birthweights of 500 to 1500 g, born between January 1991 and December 1993, who had at least one cranial ultrasound scan read independently by at least two ultrasonographers. The ultrasound data collection form diagrammed six standard coronal views. The cerebrum was divided into 17 zones in each hemisphere. All abnormalities were described as being echodense or echolucent and were classified on the basis of their size, laterality, location, and evolution. Eight percent (134/1607) of infants had at least one white-matter abnormality. The prevalence of white-matter disease decreased with increasing gestational age. Most abnormalities were small or medium sized and unilateral; only large echodensities tended to be bilateral and asymmetric. Large abnormalities, whether echodense or echolucent, were more likely than smaller abnormalities to be widespread, and the extent of cerebral involvement was independent of whether abnormalities were unilateral or bilateral. Large abnormalities were relatively more likely than small abnormalities to involve anterior planes. Small abnormalities, whether echodense or echolucent, or whether unilateral or bilateral, preferentially occurred near the trigone. Using the characteristics of location, size, and laterality/symmetry, we were able to allocate only 53% of infants with white-matter abnormalities to periventricular hemorrhagic infarction or periventricular leukomalacia. Assuming that periventricular leukomalacia and periventricular hemorrhagic infarction are independent and do not share risk factors, and that each occurs in approximately 5% of infants, we would have expected 0.25%, or about 4 individuals, to have abnormalities with characteristics of both periventricular leukomalacia and periventricular hemorrhagic infarction, whereas we found 63 such infants. Most infants with white-matter disease could not be clearly designated as having periventricular hemorrhagic infarction or periventricular leukomalacia only. Periventricular hemorrhagic infarction contributes to the risk of periventricular leukomalacia occurrence, or the two sorts of abnormalities share common risk antecedent factors. The descriptive term echodense or echolucent and the generic term white-matter disease of prematurity should be used instead of periventricular leukomalacia or periventricular hemorrhagic infarction when referring to sonographically defined white-matter abnormalities.

The filmless radiology reading room: a survey of established picture archiving and communication system sites.

The purpose of this study was to survey radiologists experienced in soft-copy diagnosis using computer workstations about their current reading room environment, their impressions of the efficacy of their reading room design, and their recommendations based on their experience for improvement of the soft-copy reading environment. Surveys were obtained from radiologists at seven sites representing three major picture archiving and communication system (PACS) vendors throughout the world that have had extensive experience with soft-copy interpretation of radiology studies. The radiologists filled out a detailed survey, which was designed to assess their current reading room environment and to provide them with the opportunity to make suggestions about improvement of the PACS reading rooms. The survey data were entered into a database and results were correlated with multiple parameters, including experience with PACS, types of modalities interpreted on the system, and number of years of experience in radiology. The factors judged to be most important in promoting radiologist productivity were room lighting, monitor number, and monitor brightness. Almost all of the radiologists indicated that their lighting source was from overhead rather than indirect or portable light sources. Approximately half indicated they had the capability of dimming the brightness of the overhead lighting. Most radiologists indicated that they were able to adjust room temperature but that they did not have individual temperature controls at their workstations. The radiologists indicated that the most troublesome sources of noise included background noise, other radiologists, and clinicians much more than noise from computer monitors, technologists, or patients. Most radiologists did not have chairs that could recline or arm rests. Most did have wheels and the capability to swivel, both of which were judged important. The majority of chairs also had lumbar support, which was also seen to be important. Radiologists commonly adjusted room lighting and their reading chair, but rarely adjusted room temperature or monitor brightness. The median number of hours spent at the workstation before taken a "break" was 1.5. Common recommendations to improve the room layout included compartmentalization of the reading room and availability of the hospital/radiology information system at each workstation. The survey data suggest several areas of potential improvement based on radiologists' experience. Optimization of soft-copy reading room design is likely to result in decreased fatigue and increased productivity.

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators.

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 x g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; fetoplacental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n = 537), or after a longer interval (n = 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born > or =1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8; p = 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9; p = 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. The Developmental Epidemiology Network.

OBJECTIVES: Because intraventricular hemorrhage (IVH) often precedes the development of sonographically defined white matter damage (WMD) in very preterm infants, we sought to identify the IVH characteristics that predict WMD. HYPOTHESES: We evaluated variations on the null hypothesis that infants with IVH are no more likely than infants without IVH to have WMD. These variations dealt with characteristics of the IVH (presence or absence of ventriculomegaly) or characteristics of the WMD (size, localization, and laterality). METHODS: A total of 1605 infants weighing 500 to 1500 g at birth between January 1991 and December 1993 underwent standardized cranial ultrasound studies with 6 standard coronal and 5 sagittal views at postnatal days 1 to 3, 7 to 10, and at 3 to 8 weeks. RESULTS: A total of 129 (8%) infants had WMD, either an echodensity alone (n = 59), an echolucency alone (n = 18), or both (n = 52). In analyses that controlled for gestational age, IVH was associated with a fivefold to ninefold increased risk of WMD regardless of size, laterality, or extent of lesions (P

Reduced risk of liver-function-test abnormalities and new gallstone formation with weight loss on 3350-kJ (800-kcal) formula diets.

Weight loss in obese subjects ingesting very-low-energy (VLE; < 2510 kJ/d), low-fat (< or = 1 g/d) formula diets is associated with liver-function-test abnormalities and gallstone formation. It is unknown whether these abnormalities develop during treatment with diets higher in energy and fat. We prospectively studied liver-function tests and gallstone formation in 73 obese patients ingesting approximately 3500 kJ and 15-25 g fat daily for 10 wk. Two of 53 patients completing the protocol developed ultrasonographic gallstones during weight loss, a rate substantially lower than that observed with VLE diets. Trend analysis demonstrated significant increases in AST and ALT activities, but changes were less than those observed with VLE diets. Patients who developed gallstones had a significantly greater weight loss rate and larger increases in AST and ALT than did nonstone-forming patients. These results suggest that the risk of developing hepatobiliary abnormalities with dieting is lowered when subjects ingest greater amounts of energy and fat than that administered in earlier VLE-diet studies. Our results also highlight potential risk factors and markers of new gallstone formation.

Ultrasonic detection of osteomyelitis. Pathologic correlation in an animal model.

The authors correlated sonographic findings with histologic findings in a rabbit model of osteomyelitis. Staphylococcus aureus osteomyelitis was induced in the femora of 11 New Zealand white rabbits. The opposite leg was used as a control. Sonographic findings showed fluid adjacent to the bone in 11 cases. The fluid was believed to be an inflammatory exudate, and its presence suggested osteomyelitis. Pathologic analysis showed extraperiosteal purulent fluid adjacent to the cortex as well as histopathologic changes of osteomyelitis in the 11 rabbits. There was one false-positive sonographic diagnosis of osteomyelitis in a rabbit that had a soft tissue abscess adjacent to the cortex.

Clinical trial of silicone-rubber gastric balloon to treat obesity.

A study was conducted to test the efficacy and safety of a 300 ml silicone-rubber gastric balloon for weight reduction. Eighty-six obese subjects were distributed into four groups: (1) gastric balloon only, (2) gastric balloon and prescribed 1000 kcal/day (239 kJ) diet, (3) 1000 kcal/day diet only, and (4) no treatment. The intervention period was 3 months. The balloon only group lost 3.2 kg +/- 0.9 (s.e.), the balloon and diet group lost 5.1 +/- 1.0 kg, the diet group lost 6.9 +/- 1.4 kg and the control group gained 0.6 +/- 0.5 kg. The three intervention groups each lost significantly more weight than the control group. The diet only group lost significantly more weight than the balloon only group. Body densitometry showed that the treatment groups lost a significant amount of body fat. Gastroscopy revealed three ulcers and two superficial erosions at balloon removal. The gastric balloons were well tolerated despite gastric spasms and nausea which abated after the initial 24-48 hours. Gastric capacity was determined in a subset of 19 subjects from the two balloon groups before the intervention by distending the stomach with a balloon and calculating the volume required to produce an increase in intragastric pressure of 5 cm H2O. Subjects with a smaller gastric capacity lost more weight with the balloon than subjects with a large capacity (r = 0.45, P less than 0.05). These results suggest that for improved efficacy, balloon volume may need to be larger than 300 ml or adjusted to the individual's gastric capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteomyelitis: detection with US.

To evaluate the role of ultrasound (US) in the detection of osteomyelitis, the authors prospectively studied 48 patients clinically suspected of having osteomyelitis. A sonographic diagnosis was made if fluid was seen directly in contact with bone, without intervening soft tissues. Twelve of the 48 patients were subsequently found to have osteomyelitis. In 10 of them, US demonstrated abnormal fluid adjacent to the bone. This fluid was thought to represent an inflammatory exudate dissecting in a subperiosteal and/or extraperiosteal location. Eight of the 48 patients had soft-tissue fluid collections. The rest of the patients either had no abnormalities or had cellulitis. The authors conclude that US can be useful in the detection of osteomyelitis.

Sequential development of multiple aortic aneurysms in a neonate post umbilical arterial catheter insertion.

A neonate in whom multiple aortic aneurysms developed as a result of umbilical arterial catheterization is presented. Initially a single aneurysm was diagnosed by ultrasound. Serial sonographic examinations showed enlargement of the first as well as formation and subsequent enlargement of additional aneurysms.

Osteomyelitis: detection with US. Work in progress.

Ten patients with clinically suspected osteomyelitis were studied with ultrasound (US). Five patients had abnormalities detectable on sonograms. An abnormal fluid collection was demonstrated adjacent to the bone in three of these five. US-guided aspiration of the fluid in two of the three patients revealed purulent or infected fluid that was thought to represent an inflammatory exudate dissecting in a subperiosteal or extraperiosteal location. Findings from subsequent radiographic and scintigraphic studies confirmed the diagnosis of osteomyelitis in these three patients. The other two patients with abnormal sonographic results had collections of fluid that were separated from the bone by a variable amount of soft tissue. These collections were confined to the soft tissue and did not appear to arise from the bone. Aspiration revealed a soft-tissue abscess in one patient and a seroma in the second. Findings in this preliminary study suggest that fluid around the bone seen on sonograms may indicate acute osteomyelitis.