Partial trisomy 1q (1q42.13-->qter) and partial monosomy 6q (6q27-->qter) in a girl with single median maxillary central incisor, corpus callosum dysgenesis and developmental delay.

A 3-year-old girl presented with mental retardation, developmental delay, seizures, hypotonia, brachycephaly, a triangular face, single median maxillary central incisor (SMMCI), prominent forehead, down-slanting palpebral fissures, hypertelorism, a high-arched palate, micrognathia and low-set ears. Computed tomographic scans revealed corpus callosum dysgenesis and hypoplasia of bilateral frontal sinuses. Oligonucleotide-based array comparative genomic hybridization analysis revealed a -20.7-Mb duplication of 1q42.13-->qter and a -3.6-Mb deletion of 6q27-->qter. The karyotype of the girl was 46,XX,der(6)t(1;6)(q42.13;q27)pat. Mutational analysis of the patient revealed no mutation in the genes of SHH, SIX3 and TGIF. The present case adds unbalanced chromosome aberration of partial trisomy 1q and partial monosomy 6q to the list of genetic conditions associated with SMMCI.

De novo satellited 2q associated with corpus callosum dysgenesis, short stature, mental retardation and developmental delay.

We report the cytogenetic and molecular characterization of a 9.46-Mb terminal deletion of 2q in a 3-year-old girl with a de novo satellited 2q (2qs), corpus callosum dysgenesis, short stature, mental retardation and developmental delay. We speculate that haploinsufficiency of HDAC4 is responsible for short stature, mental retardation and developmental delay, and haploinsufficiency of EFHD1 is most likely responsible for the phenotype of corpus callosum dysgenesis in this patient.

Identification of a missense mutation of c.3064G>A, Gly1022Ser in exon 43 of COL1A1 gene in a girl with osteogenesis imperfecta type III.

Osteogenesis imperfecta (OI) types I-V have been inherited in an autosomal dominant pattern. OI type I is associated with mutations in COL1A1 mostly due to a null allele. OI types II-IV are associated with mutations in COL1A1 or COL1A2 and mostly are due to glycine substitutions. It has been suggested that the effect of glycine substitutions is position specific, and the substitution of glycine by serine has much less lethal effect than the substitutions by valine, aspartic acid, glutamic acid, arginine and cysteine. We report identification of c.3064G>A, GGT>AGT, Gly1022Ser (Gly(844) --> Ser844 in triple helix) in exon 43 of the COL1A1 gene in an 8-year-old girl with OI type III. Our report provides evidence that at triple helix glycine residue 844 (p.Gly1022), a glycine substitution by serine can result in OI type III but not a lethal outcome.

Phenotypic features of pure 9p deletion in a male infant include cryptorchidism, congenital heart defects and postaxial polydactyly.

We report a 2 1/2-year-old male infant with a karyotype of 46,XY,del(9)(p22) and the phenotypic features of craniofacial dysmorphisms, hypotonia, psychomotor developmental delay, mental retardation, ventricular septal defect, atrial septal defect, cryptorchidism and postaxial polydactyly of the fingers. A rudimentary poorly developed extra digit in the ulnar side of the fifth finger was observed in each hand. The present case adds to the literature of postaxial hexadactyly of the fingers in chromosome 9p deletion syndrome. We suggest that 9pter-p22 may contain genetic loci associated with human postaxial polydactyly.

Partial monosomy 9p (9p22.2-->pter) and partial trisomy 18q (18q21.32-->qter) in a female infant with anorectal malformations.

We report a female infant with a karyotype of 46,XX,der(9)t(9;18)(p22.2;q21.32)pat and the phenotypic features of craniofacial dysmorphisms, developmental delay, hypotonia, horizontal nystagmus, strabismus, congenital heart defects, clubfoot, and anorectal malformations with an anterior ectopic anus and a stenosed anal opening. Array comparative genomic hybridization revealed a 16.93-Mb deletion at 9p24.3-p22.2 encompassing the FREM1 gene and a 20.43-Mb duplication at 18q21.32-q23 encompassing the PIGN gene. We speculate that dual genome imbalances in FREMI at 9p22.3 and in PIGN at 18q21.3 are most likely responsible for the abnormal development of anorectum in this patient.

Pure distal 9p deletion in a female infant with cerebral palsy.

We report cytogenetic and molecular characterization of a 15.63-Mb pure distal deletion of chromosome 9p (9p22.3-->pter) in a l 1/2-year-old female infant with cerebral palsy and diffuse cerebral dysfunction. The deletion is of paternal origin and encompasses the genes of ANKRDS15, DOCK8, FOXD4 and VLDLR. We discuss the genotype-phenotype correlation in this case with neurological dysfunction and a distal 9p deletion of paternal origin.

Pure distal 11q deletion without additional genomic imbalances in a female infant with Jacobsen syndrome and a de novo unbalanced reciprocal translocation.

We report a neonate with pure deletion of distal 11q (11q23.3-->qter) and Jacobsen syndrome. The patient had growth restriction, petechiae, thrombocytopenia, dilation of renal pelvis, congenital heart defects, and seizures. Array comparative genomic hybridization revealed a 15.8-Mb deletion from 11q23.3 to 11q25 without genomic imbalances in other chromosomes. Cytogenetic analysis revealed a karyotype of 46,XX,der(7)(7pter-->7q32),der(11)(11pter--> 11q23.3::7q32-->7qter). The parental karyotypes were normal. This is the first report of pure distal 11q deletion without additional genomic imbalances in a patient with Jacobsen syndrome and a de novo unbalanced reciprocal translocation.

Partial monosomy 3p (3p26.2 --> pter) and partial trisomy 5q (5q34 --> qter) in a girl with coarctation of the aorta, congenital heart defects, short stature, microcephaly and developmental delay.

A 1-year-and-3-month-old girl presented with psychomotor retardation, developmental delay, clinodactyly of the thumb, coarctation of the aorta, patent ductus arteriosus, peripheral pulmonary stenosis, atrial septal defect, microcephaly, brachycephaly, a small oval face, almond-shaped eyes, a down-turned mouth, a widened nasal bridge, hypertelorism, epicanthic folds, long philtrum, low-set large ears and but no craniosynostosis. Oligonucleotide-based array comparative genomic hybridization revealed a -4.79-Mb deletion of 3p26.2 --> pter encompassing CHL1 and CNTN4, and a -19.56-Mb duplication of 5q34 --> qter encompassing MSX2, NKX2-5 and NSD1. The karyotype of the girl was 46,XX,der(3)t(3;5)(p26.2;q34) pat. The present case adds distal 5q duplication to the list of chromosome aberrations associated with coarctation of the aorta.

Increased risk of cardiovascular disease in Type 1 diabetes: arterial exposure to remnant lipoproteins leads to enhanced deposition of cholesterol and binding to glycated extracellular matrix proteoglycans.

AIMS: To determine fasting and postprandial metabolism of apolipoprotein B48 (apoB48) remnant lipoproteins in subjects with Type 1 diabetes and the relationship to progressive cardiovascular disease, and to investigate the impact of remnant lipoprotein cholesterol accumulation associated with arterial wall biglycan using a rodent model of Type 1 diabetes. METHODS: Normolipidaemic subjects (n = 9) with long-standing Type 1 diabetes (and advanced cardiovascular disease) and seven healthy control subjects were studied. Fasting and postprandial apoB48 concentration was determined following a sequential meal challenge. A rodent model of streptozotocin-induced diabetes was used to investigate the ex vivo retention of fluorescent-conjugated remnants. Binding of remnant lipoproteins to human recombinant biglycan was assessed in vitro. RESULTS: A significantly higher concentration of fasting plasma apoB48 remnants was observed in patients with Type 1 diabetes compared with control subjects. Patients with Type 1 diabetes exhibited a greater total plasma apoB48 area under the curve (AUC) and an increased incremental AUC following a second sequential meal compared with control subjects. The arterial retention of remnants ex vivo and associated cholesterol was increased sevenfold in Type 1 diabetes rats relative to controls. Remnants were shown to bind with significant affinity to human biglycan in vitro and a further 2.3-fold increased binding capacity was observed with glycated biglycan. Remnants were shown to colocalize with both arterial biglycan and glycated matrix proteins in the Type 1 diabetes rodent model. CONCLUSION: Impaired metabolism of remnant lipoproteins associated with enhanced binding to proteoglycans appears to contribute to the arterial cholesterol deposition in Type 1 diabetes. Our findings support the hypothesis that impaired remnant metabolism may contribute to accelerated progression of atherosclerosis in the hyperglycaemic and insulin-deficient state.

Open window thoracostomy: modern update of an ancient operation.

INTRODUCTION: In modern day thoracic surgical practice, better understanding of the pathophysiology of intrathoracic infections, improved antibiotic therapy and advancements in thoracic surgical techniques have decreased the use of procedures such as open window thoracostomy (OWT). Despite this, there are occasions where OWT cannot be avoided, and it is of interest where its current utility lies. To determine the current efficacy of OWT, we reviewed our recent experience with a focus on the indications, timing of surgery, effectiveness in clearing infection, patient survival, and timing of closure. METHODS: After Institutional Review Board approval, charts of 78 patients were reviewed. Dates reviewed were from 1/1/1998 to 1/1/2008. Patients were predominantly male (66 %) with a median age 58 years. Median time from initial diagnosis to OWT was 70 days (range 1 to 720 days). RESULTS: Primary indication for surgery was empyema in 75 (96 %), and most patients had previous thoracic surgery. The most frequent causes of empyema were post-pneumonectomy (n = 25), post-pneumonic (n = 14), and post-lobectomy (n = 9). Bronchopleural fistulae were present in 29 (37 %) cases. Lung cancer was diagnosed in 34 (45 %) patients, and 24 underwent perioperative radiation therapy. Patient survival at 1 month, 6 months, 1 year and 5 years was 94 %, 82 %, 74 % and 60 %, respectively, with an in-hospital mortality of 6.4 %. Infection was controlled in nearly all patients (n = 72). Fifteen (19 %) patients underwent surgical closure for OWT; in 2 (2.6 %), OWT closed spontaneously. CONCLUSIONS: Currently, open window thoracostomy is used to treat complex empyema incurred from pulmonary resection, cancer and/or infection in patients that cannot be managed by more conservative strategies. Overall mortality and morbidity rates are acceptable in this debilitated patient group.

Allograft entrapment after lung transplantation: a simple solution using a pleurocutaneous catheter.

BACKGROUND: Chronic pleural effusion following lung transplantation (LTx) is often responsible for respiratory insufficiency and can lead to lung entrapment. Decortication carries considerable morbidity, and extended use of tube thoracostomy is not practical. We have utilized an indwelling pleurocutaneous catheter in the setting of intractable post-transplant effusion and have reviewed our experience to determine whether this strategy: 1) facilitates resolution of effusion, and 2) adequately palliates lung entrapment. METHODS: Twelve PleurX (Denver Biomedical, Golden, CO, USA) catheters were placed in 9 LTx patients (6 unilateral, 3 bilateral) for refractory pleural effusions after standard tube thoracostomy drainage failed (12/12). Two-thirds of the patients (8/12) also had concomitant lung entrapment. RESULTS: There was no operative mortality. Median time from LTx to catheter placement was 79 days (range 21-769). Catheter use achieved the desired outcome in 11/12 placements. Catheters remained in place for a median of 86 days (range 35-190). Direct catheter-related complications included hemothorax (1) and empyema (1). CONCLUSION: Use of an indwelling pleurocutaneous catheter effectively achieves its intended goals of pleurodesis and management of entrapped lungs after LTx.

Methods to assess impaired post-prandial metabolism and the impact for early detection of cardiovascular disease risk.

Post-prandial lipaemia has emerged as a key contributor to cardiovascular disease (CVD) risk and progression. Specifically, delayed clearance of chylomicrons (CM) and their remnants increase the delivery of triglyceride and cholesteryl ester to the vessel wall and can accelerate the progression of atherosclerosis, which may be particularly pertinent to individuals with insulin resistance and/or obesity. As the number of studies linking post-prandial metabolism and chronic disease increases, interest has grown in the use of parameters reflecting CM metabolism as a possible indicator of early CVD risk. This, in turn has raised the question of what method might be most appropriate to detect CM and their remnants in plasma accurately. However, the handful of techniques able to measure CM metabolism (triglyceride-rich lipoprotein fractions; remnant-lipoprotein cholesterol; retinyl esters, CM-like emulsion; sodium dodecyl sulphate-polyacrylamide gel electrophoresis; immunoblotting, enzyme-linked immunoabsorbent assays; C(13) breath test; capillary finger prick) differ in their specificity, cost and applicability in research and in the clinical setting. In this review, we explore the scientific and clinical implications of CM methodology to better understand early risk assessment of CVD. We raise ongoing issues of the need to appreciate differential separation of very low-density lipoprotein and CM fractions, as well as to identify the technical basis for imprecision between assays for apolipoprotein B48. We also highlight emerging issues with respect to the practicality of measuring post-prandial metabolism in large clinical studies and offer opinions on the appropriateness of existing techniques in this field.

Intercellular communication is cell cycle modulated during early Xenopus laevis development.

We investigated intercellular communication during the seventh and tenth cell cycles of Xenopus laevis development using microinjection of Lucifer yellow and FITC-dextran as well as freeze-fracture electron microscopy. We found that gap junction-mediated dye coupling visualized using Lucifer yellow was strongly cell cycle modulated in the tenth cell cycle. Cytoplasmic bridge-mediated dye coupling visualized via FITC-dextran was also, of course, cell cycle modulated. The basis of cell cycle-modulated gap junctional coupling was investigated by measuring the abundance of morphologically detectable gap junctions through the tenth cell cycle. These proved to be six times more abundant at the beginning than at the end of this cell cycle.

Large-scale turbulence structures in a laboratory-scale boundary layer under steady and gusty wind inflows.

Experiments on turbulence structures and features of a wind field under steady inflow and gusty wind inflows were implemented in a straight-through wind tunnel. Streamwise and wall-normal velocity components were measured using a streamline constant temperature anemometer (streamline CTA). Power spectra analyses revealed the existence of very large-scale motions (VLSMs) under both steady and gusty wind inflows; but new gusty scale motions (GSMs) were revealed under only gusty wind inflows. The GSMs might originate from an ordered external driving force that forces hairpin packets to align coherently in groups with a length scale related to the gust inflow condition. The streamwise wavelength of VLSMs is independent of inflow conditions, while the turbulent energy of VLSMs is associated with the wall-normal height and local mean streamwise velocity. In particular, the streamwise wavelength of GSMs increases linearly with the average value and period of sinusoidal gusty wind inflows, and the turbulent energy of GSMs is sensitive to the wall-normal height and all characteristic parameters of gusty wind inflows, including the average value, amplitude and period. Considerable wall-normal airflows induced by gusty wind inflows were detected and these are negatively correlated with the variation in gusty streamwise velocity, and root mean square (RMS) values of the gusty wall-normal velocity tended to increase linearly with the average value and amplitude of gusty wind inflows.

Repair of cardiac defects through a shorter right lateral thoracotomy in children.

BACKGROUND: Median sternotomy is a conventional approach for correction of cardiac defects for many years; however, the cosmetic result is poor. Therefore, right lateral thoracotomy was tested as an alternative procedure with a better cosmetic outcome. METHODS: Between October 1994 and February 1999, 683 patients underwent correction of congenital cardiac malformations during a cardiopulmonary bypass through right lateral thoracotomy involving a shorter incision through the third or the fourth intercostal space. All of the patients were children. The average age was 3.26+/-1.67 years (range, 4 months to 7 years). The average weight was 13.59+/-4.37 kg (5 to 40). The patients had various cardiac defects and associated anomalies. RESULTS: Only 2 patients died after operation, 1 from low cardiac output and the other from severe pulmonary infection. The hospital morbidity was lower. The mean cardiopulmonary bypass time was 58.67+/-35.11 minutes (range, 16 to 430 minutes), the mean aortic cross-clamping time was 35.03+/-24.84 minutes (range, 3 to 205 minutes). The postoperative average mechanical ventilation time was 19.23+/-39.11 hours (range, 2 to 391 hours), and the mean postoperative stay was 8.55+/-12.54 days (range, 5 to 293 days). CONCLUSIONS: The right lateral thoracotomy incision is a safe and effective alternative to a median sternotomy for correction of cardiac defects. Advantages of this approach compared with median sternotomy are less injury, maintenance of the continuity and the integrity of the bony thorax, and prevention of the development of "pigeon-chesting." The scar is less visible, hence, the cosmetic result can meet patient expectations. This procedure is consistent with the idea of minimal invasive surgery.

Evaluation of germ-cell kinetics in infertile patients with proliferating cell nuclear antigen proliferating index.

AIM: To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathological diagnosis and treatment of male infertility. METHODS: Testicular biopsy specimen obtained from 48 cases of male infertility and 2 normal controls were fixed and embedded. The sections were stained with anti-PCNA monoclonal antibodies or haematoxylin/eosin. Proliferating index (PI), expressed as the percentage of germ-cell nuclei positively stained with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600 germ-cells. RESULTS: The infertile patients were divided into 4 groups: Group 1, normal spermatogenesis (14 cases); Group 2, hypospermatogenesis (16 cases); Group 3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The PCNA PI of normal control testis was 86.5% (mean value). Group 3 had a significantly lower PCNA PI (29.8%) than normal testis; Group 1 and 2 had similar PIs (82.3% and 82.3%, respectively) as the control testis. PI of the negative control (Group 4) was 0 as no germ-cells were found. CONCLUSION: PCNA PI is useful for assessing germ-cell kinetics, especially for pathological diagnosis of germinal arrest which is difficult to differentiate by routine HE staining technique. In germinal arrest, there is a significantly lowered PCNA PI, which is an indication of DNA synthesis deterioration, suggesting the use of therapies be different from those for hypospermatogenesis.

A prospective evaluation of surgeon performed sonography as a screening test in blunt abdominal trauma.

INTRODUCTION: Sonography has found a role in the evaluation of patients with abdominal injury. However, the accuracy of sonography as performed by non-radiologists remains controversial. This study aims to determine the accuracy of focused abdominal sonography for trauma when performed by surgeons. MATERIALS AND METHOD: Over a 1-year period, 48 patients with abdominal injury were initially evaluated for free intraperitoneal fluid by sonography. These tests were performed by 2 surgeons who had received instructions and performed a minimum of 30 examinations. Sonographic findings were then compared with other diagnostic modalities including computed tomography (CT) scan, diagnostic peritoneal lavage and exploratory laparotomy. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for sonography were found to be 0.86, 0.92, 0.89, 0.90 and 0.89, respectively. Although not specifically sought for, 2 cases of solid organ injury and 1 haemothorax, which were missed in initial examinations and X-rays, were detected on sonography. CONCLUSION: In conclusion, our initial experience suggests that local surgeons can perform a focused sonographic examination for trauma with acceptable accuracy. Although sonography lacks the sensitivity of diagnostic peritoneal lavage and the accuracy of CT scan, the diagnostic algorithm for abdominal trauma should include sonography as a screening test.