Kernicterus with abnormal high-signal changes bilaterally in the globus pallidus: A case report.

Kernicterus is a relatively rare consequence of hyperbilirubinemia. There is an important role for MRI imaging for this entity in the appropriate clinical context as there are distinct signal changes in the globus pallidus. A case report and image findings are presented

Quantitative CT densitometry for predicting intracerebral hemorrhage growth.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage growth independently predicts disability and death. We hypothesized that noncontrast quantitative CT densitometry reflects active bleeding and improves predictive models of growth. MATERIALS AND METHODS: We analyzed 81 of the 96 available baseline CT scans obtained <3 hours post-ICH from the placebo arm of the phase IIb trial of recombinant factor VIIa. Fifteen scans could not be analyzed for technical reasons, but baseline characteristics were not statistically significantly different. Hounsfield unit histograms for each ICH were generated. Analyzed qCTD parameters included the following: mean, SD, coefficient of variation, skewness (distribution asymmetry), and kurtosis ("peakedness" versus "flatness"). These densitometry parameters were examined in statistical models accounting for baseline volume and time-to-scan. RESULTS: The coefficient of variation of the ICH attenuation was the most significant individual predictor of hematoma growth (adjusted R(2) = 0.107, P = .002), superior to BV (adjusted R(2) = 0.08, P = .006) or TTS (adjusted R(2) = 0.03, P = .05). The most significant combined model incorporated coefficient of variation, BV, and TTS (adjusted R(2) = 0.202, P = .009 for coefficient of variation) compared with BV and TTS alone (adjusted R(2) = 0.115, P < .05). qCTD increased the number of growth predictions within ±1 mL of actual 24-hour growth by up to 47%. CONCLUSIONS: Heterogeneous ICH attenuation on hyperacute (<3 hours) CT imaging is predictive of subsequent hematoma expansion and may reflect an active bleeding process. Further studies are required to determine whether qCTD can be incorporated into standard imaging protocols for predicting ICH growth.

Survival of benthic foraminifera under hypoxic conditions: results of an experimental study using the CellTracker Green method.

We present results of an experimental study, in which benthic foraminiferal faunas have been kept under strongly hypoxic conditions. Sixteen short sediment cores from a 35m deep site in the Adriatic Sea were incubated for a maximum of 69days. Some of the cores were air-bubbled and remained well oxygenated throughout the experiment. The other cores were bubbled with nitrogen; the overlying waters of these cores became strongly hypoxic, whereas the sediment remained virtually without oxygen. Live foraminifera have been inventoried with the CellTracker Green method. Our results show that all dominant taxa survive strongly hypoxic conditions. Nouria polymorphinoides and Nonionella turgida show a clear tendency to move to the sediment surface in the nitrogen-bubbled cores, whereas Bulimina spp. and Eggerella scabra do not show such a migrational response. We suggest that this is a response to the concentration of nutritional resources at the sediment-water interface.

Prophylaxis against infection in cataract surgery: a survey of routine practice.

PURPOSE: To survey the routine practice of consultant ophthalmic surgeons in the United Kingdom in preventing postoperative endophthalmitis following cataract surgery. METHODS: This is a cross-sectional questionnaire-based study. A questionnaire was sent to consultant ophthalmic surgeons in university teaching hospital ophthalmology departments in the United Kingdom. RESULTS: Questionnaires were sent to 391 consultant ophthalmic surgeons in 36 ophthalmology departments. The response rate was 55.0% (215 responses). Eleven (5.1%) did not perform cataract surgery routinely. Of the remaining 204 respondents, all performed phacoemulsification as routine. A total of 28 (13.7%) reported a 0% rate of postoperative infective endophthalmitis. Preoperative topical antibiotics were routinely prescribed by 12 respondents (5.9%). The most common immediately preoperative measure was the usage of povidone iodine (203 respondents, 99.5%). A total of 19 (9.3%) used an antibiotic infusion during surgery. Postoperative subconjunctival antibiotics were given by 138 (67.6%), most commonly cefuroxime. A total of 33 (16.2%) administered postoperative intracameral antibiotics. A total of 141 (69.1%) prescribed topical antibiotics after surgery, most commonly neomycin. None gave systemic antibiotics routinely pre-or postoperatively. CONCLUSIONS: The results show a wide variation of prophylactic measures used in the United Kingdom. The routine practices adopted reflect personal preferences, and were not necessarily evidence-based. Further prospective studies are required to provide evidence for the efficacy of these prophylaxis techniques.

Vascular trauma in Penang and Kuala Lumpur Hospitals.

OBJECTIVES: The nature of vascular trauma varies greatly between continents and across time. The aim of this study was to prospectively analyse the demographics, pathology, management and clinical outcomes of vascular injuries in two urban Malaysian hospitals and review of international literature on vascular trauma. From this information, preliminary management and preventive implications will be described. METHODS: Eighty-four consecutive cases of trauma requiring vascular surgery were prospectively analysed over three years at Hospital Kuala Lumpur and Hospital Pulau Pinang, Malaysia. Extensive patient demographic and injury data, including the mechanism of injury, associated injuries, angiographic findings, operative details and post-operative complications, were systematically gathered. RESULTS: Most vascular injuries were incurred by males (76/84), with 37% (28/76) of them aged between 21 and 30 years. Malays were most frequently injured (n = 36) followed by Chinese and Indians. Road traffic accidents (n = 49) substantially outnumbered all other causes of injury. Lower limb injuries (n = 57) occurred more than twice as often as upper limb injuries (n = 27). Complete arterial transections (n = 43) and intimal injuries (n = 27) were more common than arterial lacerations (n = 10) and pseudoaneurysms (n = 4). The most frequently damaged vessels were the popliteal/tibioperoneal trunk (n = 33). All patients received urgent Doppler ultrasound assessment and, where possible, ankle-brachial systolic index measurement. Of all patients, 40 received an angiogram, haemodynamic instability making this investigation impractical in others. Primary arterial repair was the most frequently employed surgical procedure (n = 54) followed by autogenous reverse long saphenous vein (LSV) interposition graft (n = 14), embolectomy (n = 5) and PTFE interposition graft (n = 3). The most common post-operative complication was wound infection (n = 11). Amputation, as a last resort, was required in 13 cases following either primary or autogenous reverse LSV repair complicated by sepsis or critical ischaemia. CONCLUSIONS: Vascular trauma, especially in conjunction with severe soft tissue, nerve or orthopaedic injury carries colossal physical, psychological, financial and social costs. Associated nerve and venous injury portended poor outcome in this study. Whilst orthopaedic trauma was a common association, the concurrence of occult vascular trauma and soft tissue injury without fracture emphasises the crucial importance of thorough and rapid clinical vascular assessment, investigation and surgical intervention. Fasciotomy, especially for the lower limb, is important for the prevention of compartment syndrome and its, limb-threatening sequelae. Primary preventive road safety promotion and interventions, with attention to high-risk groups (young males and motorcyclists), is urgently required.

Value of nasal endoscopy and probing in the diagnosis and management of children with congenital epiphora.

BACKGROUND: Congenital nasolacrimal obstruction is usually the result of failure of canalisation of the distal end of the nasolacrimal duct. The most common outcome is spontaneous resolution, but some children do require surgical treatment by probing. Probing is a blind procedure with a recognised failure rate. METHODS: In 52 lacrimal systems of 40 children nasal endoscopy was combined with a "stepwise" systematic probing in an attempt to improve the outcome and reduce the number of repeat procedures. RESULTS: Combined nasal endoscopy and probing improved the understanding of outflow obstruction in young children. The success of the procedure depended upon the level of the obstruction within the outflow system. Formation of a false passage was seen in six cases (15%). The probe was rerouted under direct visualisation in these cases to form a functioning passage. Reasons for failure were identified in those who did not have a successful outcome and only one repeat procedure was required. CONCLUSION: Using nasal endoscopy the area of lacrimal outflow obstruction at the lower end of the nasolacrimal duct can be observed directly and it is possible to guide the progress of probing under direct vision. This gives better information about the nature of the obstruction, minimises the formation of false passages, and allows a wider range of treatment options under a single anaesthetic.

The mouse brain transcriptome by SAGE: differences in gene expression between P30 brains of the partial trisomy 16 mouse model of Down syndrome (Ts65Dn) and normals.

Trisomy 21, or Down syndrome (DS), is the most common genetic cause of mental retardation. Changes in the neuropathology, neurochemistry, neurophysiology, and neuropharmacology of DS patients' brains indicate that there is probably abnormal development and maintenance of central nervous system structure and function. The segmental trisomy mouse (Ts65Dn) is a model of DS that shows analogous neurobehavioral defects. We have studied the global gene expression profiles of normal and Ts65Dn male and normal female mice brains (P30) using the serial analysis of gene expression (SAGE) technique. From the combined sample we collected a total of 152,791 RNA tags and observed 45,856 unique tags in the mouse brain transcriptome. There are 14 ribosomal protein genes (nine under expressed) among the 330 statistically significant differences between normal male and Ts65Dn male brains, which possibly implies abnormal ribosomal biogenesis in the development and maintenance of DS phenotypes. This study contributes to the establishment of a mouse brain transcriptome and provides the first overall analysis of the differences in gene expression in aneuploid versus normal mammalian brain cells.

Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region.

An autosomal recessive nonsyndromic deafness locus, DFNB10, was previously localized to a 12-cM region near the telomere of chromosome 21 (21q22.3). This locus was discovered in a large, consanguineous Palestinian family. We have identified and ordered a total of 50 polymorphic microsatellite markers in 21q22.3, comprising 16 published and 34 new markers, precisely mapped and ordered on BAC/cosmid contigs. Using these microsatellite markers, the locus for DFNB10 has been refined to an area of less than 1 Mb between markers 1016E7.CA60 and 1151C12.GT45. Six previously published cDNAs were mapped to this critical region, and their genomic structures were determined to facilitate mutation analysis in DFNB10. All six genes in this region (in order from centromere to telomere: White/ABCG1, TFF3, TFF2, TFF1, PDE9A, and NDUVF3) have been screened and eliminated as candidates for DFNB10. The new microsatellite markers and single nucleotide polymorphisms identified in this study should enable the refined mapping of other genetic diseases that map to 21q22.3. In addition, the critical region for DFNB10 has been reduced to a size amenable to an intensive positional cloning effort.

The technique of nasendoscopy in the evaluation of nasolacrimal duct obstruction in children.

Epiphora in infancy is most commonly the result of failure of canalisation of the nasolacrimal duct and most cases resolve spontaneously within 12 months. Lacrimal probing is the standard operative treatment when conservative expectant management fails. While this carries a high success rate, it does not reliably localise the site of obstruction, can create a false passage and may induce traumatic stenosis in the lacrimal passages. Nasendoscopy in conjunction with the lacrimal probing overcomes these problems as the procedure is performed under direct vision. The precise site of opening of the nasolacrimal duct is ascertained, the nature of obstruction established and the risks of false passage creation minimised. We report this technique of endoscopic assessment of lacrimal probing, and the outcome results of twenty such procedures performed on thirteen children.

Nitinol - its use in vascular surgery and other applications.

OBJECTIVES: to describe the physical properties of shape-memory alloys and the surgical, scientific and commercial applications of nitinol, in particular. DESIGN AND METHODS: a Medline, Internet and library search with contributions from commerce to describe the alloy's structure, behaviour and biocompatibility, and design for devices constructed from nitinol. RESULTS: nitinol has the properties of thermal shape memory and superelasticity that make it ideal for many vascular and general surgical prostheses and disposables, and for various commercial applications. CONCLUSIONS: further research into shape-memory alloys from scientific and commercial groups should widen their use in vascular and endovascular surgery.

Upper gastrointestinal bleeding in Kuala Lumpur Hospital, Malaysia.

Despite advancements in endoscopy and pharmacology in the treatment of peptic ulcer disease the overall mortality has remained constant at 10% for the past four decades. The aim of this study was to determine the age, gender, racial distribution, incidence and causes of endoscopically diagnosed cases of upper gastrointestinal (UGI) bleeding to summarise treatments undertaken and to report their outcome. A prospective study of UGI bleeding in 128 patients was performed in two surgical wards of Kuala Lumpur Hospital, involving both elective and emergency admissions. The study group comprised of 113 (88.2%) males and 15 (11.7%) females. The mean age was 51.9 years (range 14 to 85 years) and 37.5% (48 of 128 patients) were older than 60 years. The Indian race was over-represented in all disease categories. Smoking (50.1%), alcohol consumption (37.5%), non-steroidal anti-inflammatory drugs (NSAIDs) (17.2%), traditional remedies (5.5%), anti-coagulants (2.3%) and steroids (0.8%) were among the risk factors reported. Common presenting symptoms and signs included malaena (68.8%), haematemesis (59.4%) and fresh per rectal bleeding (33.6%). The commonest causes of UGI bleeding were duodenal ulcer (32%), gastric ulcer (29.7%), erosions (duodenal and gastric) (21.9%), oesophageal varices (10.9%) and malignancy (3.9%). UGI bleeding was treated non-surgically in 90.6% of cases. Blood transfusions were required in 62.6% (67/107) of peptic ulcer disease patients. Surgical intervention for bleeding peptic ulcer occurred in around 10% of cases and involved under-running of the bleeding vessel in most high risk duodenal and gastric ulcer patients. The overall mortality from bleeding peptic ulcer disease was 4.7%. Six patients died from torrential UGI haemorrhage soon after presentation, without the establishment of a cause. Active resuscitative protocols, early endoscopy, more aggressive interventional therapy, early surgery by more senior surgeons, increasing intensive care unit beds and more active participation of multidisciplinary teams in co-ordinating management are among remedial measures advocated. Broader educational preventive strategies should target the causes of UGI bleeding.

Mutation analyses of North American APS-1 patients.

Autoimmune polyendocrinopathy syndrome type 1 (APS-1; MIM# 240300) is a rare autosomal recessively inherited disease characterised by destructive autoimmune diseases of endocrine glands. The gene responsible for APS-1, known as AIRE (for autoimmune regulator), was recently identified and contains motifs suggestive of a transcription regulator. To date, nine APS-1-associated mutations have been identified in the AIRE gene, including two common mutations R257X and 1094-1106del. In addition to these two mutations, we report seven novel mutations in 16 APS-1 patients from North America. We found that 1094-1106del and R257X were the most common mutations in this population of mixed geoethnic origin, accounting for 17/32 and 4/32 alleles, respectively. Haplotype analyses suggest that both are recurrent mutations, occurring on several different haplotypes with closely linked markers. All the novel mutations appear to be rare, occurring in only single APS-1 families. After examining all coding sequences and exon/intron boundaries of the AIRE gene, the other APS-1 allele remained unidentified in three patients. Genotype-phenotype correlations for APS-1 remain difficult, suggesting that other genetic or environmental factors, or both, influence the clinical presentation and disease progression in individual APS-1 patients.

Lipopolysaccharide binding protein as a marker of inflammation in synovial fluid of patients with arthritis: correlation with interleukin 6 and C-reactive protein.

OBJECTIVE: To determine levels of lipopolysaccharide binding protein (LBP) in serum and in synovial fluid (SF) of patients presenting with various articular disorders [degenerative arthritis, rheumatoid arthritis (RA), reactive arthritis (ReA)] and to correlate these levels with C-reactive protein (CRP) and interleukin 6 (IL-6), 2 markers of the acute phase response. METHODS: LBP was measured by a radioimmunoassay made up of lipopolysaccharide (LPS) to capture LBP and radiolabelled anti-LBP antibodies to detect LBP. LBP was also measured for its ability to present fluorescein isothiocyanate LPS (FITC-LPS) to human monocytes. CRP was measured by nephelometry and IL-6 bioassay. RESULTS: Levels of LBP in serum and in SF were significantly higher in patients with RA and ReA than in the control group of degenerative arthropathies. In the latter group, LBP values were similar to those found in controls. Serum LBP values correlated positively with SF LBP values. LBP values also correlated with CRP and IL-6 levels measured in SF. Functionally, LBP was found to be active and able to present LPS to monocytes, resulting in tumor necrosis factor-alpha (TNF-alpha) release upon LPS challenge. CONCLUSION: These in vitro data support the observation that LBP could play a major role in local joint disorders. Our results also strengthen the view that LBP may be a new marker of synovial inflammation.

Lipopolysaccharide (LPS)-binding protein in human serum determines the tumor necrosis factor response of monocytes to LPS.

Lipopolysaccharide (LPS)-binding protein (LBP) and CD14 represent key elements in monocyte activation by LPS. The mean concentration of LBP was 18.1 microgram/mL in normal serum and 40-60 micrograms/mL in serum of patients with septic shock, independent of the fact that patients had gram-negative or other infections. Ten percent normal serum presented large concentrations of LPS (in the microgram range) to monocytes. Only when diluted 1:100 was LBP in plasma a limiting factor for monocyte activation, as measured by tumor necrosis factor (TNF) release. When LBP was depleted from serum with anti-LBP antibodies, the resulting serum did not support TNF release of monocytes upon LPS challenge. In conclusion, monocyte activation resulting in TNF secretion was related to LBP, which is abundantly present in normal serum, and elevated two to three times in patients with septic shock.

Mode of action of anti-lipopolysaccharide-binding protein antibodies for prevention of endotoxemic shock in mice.

Lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of monocytes to LPS in vitro. In a previous study, polyclonal anti-LBP IgGs were found to protect D-galactosamine-sensitized mice against a lethal endotoxemic shock induced by a low challenge of LPS or lipid A when administered simultaneously with endotoxin. In the present study, we investigated the mode of action of these anti-LBP IgGs. In vitro, we demonstrated that they interfere with LPS binding to monocytes or polymorphonuclear cells in different ways: by the mere prevention of binding of LPS to LBP thus preventing the binding of LPS to CD14, or by reacting with LPS-LBP complexes thus mediating their binding to complement or Fc receptors on monocytes and on polymorphonuclear cells. In vivo, we demonstrated that anti-LBP IgGs afforded protection against lethal endotoxemic shock by one of two mechanisms. First, LBP blockade by pretreatment with anti-LBP IgG allowed protection against a low dose of LPS (100 ng). This protection occurred despite LPS levels in blood similar to those in control mice but in the absence of detectable tumor necrosis factor (TNF). This demonstrated that anti-LBP IgG could block the LBP-mediated TNF release upon LPS challenge. In contrast, anti-LBP IgG did not afford protection in mice not sensitized with D-galactosamine and challenged with high-dose LPS (1 mg), confirming that LPS at high concentrations could stimulate cells independently of the LBP pathway. Second, anti-LBP treatment administered simultaneously with LPS challenge protected mice against both low and high doses of LPS. Unlike after pretreatment with anti-LBP IgG, this protection was accompanied by a decrease of circulating LPS, suggesting that anti-LBP IgG in these conditions facilitated clearance of LPS probably by clearing LPS-LBP complexes. These data and the fact that LBP binds to all LPS through lipid A suggest that antibody directed to LBP could be a candidate for therapeutic strategies in endotoxemic shock.

Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes.

Purified cell walls representing a wide variety in teichoic acid and peptidoglycan structure prepared from eight different gram-positive bacterial species induced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 from human monocytes in the presence of 10% plasma or serum. Significant amounts of cytokines began to be produced at concentrations above 100 ng to 1 microgram of cell walls per ml, with maximal production requiring 10 to 100 micrograms of cell wall material per ml. In the absence of plasma, the cytokine-inducing capacity of cell wall preparations was lower by at least an order of magnitude. The serum-derived cofactor was inactivated by heating at 90 degrees C for 30 min, suggesting that the activity is associated with a protein. On the other hand, replacement of normal with hypogammaglobulinemic plasma, inactivation of complement (at 56 degrees C), and blockade by the monoclonal antibody MY4 of the CD14 receptors on monocytes did not inhibit the production of TNF-alpha induced by whole cell walls. Cell walls also stimulated production of TNF-alpha induced by whole cell walls. Cell walls also stimulated production of TNF-alpha in the presence of polymyxin B, and macrophages derived from the lipopolysaccharide-insensitive cell line of C3He/HeJ mice also produced this cytokine when stimulated by cell walls. Both peptidoglycan and the soluble glycan-teichoic acid component prepared by an enzymatic method from the same wall preparation exhibited a serum-dependent induction of TNF-alpha from monocytes, while stem peptides and disacharride peptides had only poor, if any, activity. Cell walls may contribute to the septic shock induced by gram-positive bacteria.

Lipopolysaccharide-binding protein as a major plasma protein responsible for endotoxemic shock.

Because lipopolysaccharide (LPS)-binding protein (LBP) sensitizes monocytes to LPS in vitro, it has been suggested that LBP initiates host defenses against Gram-negative bacteria. The role of LBP in vivo, and particularly in endotoxemic shock, is unknown, however. Therefore an IgG against murine LBP was prepared. It was found to neutralize binding of LPS and subsequent activation of murine macrophages in vitro. This anti-LBP protected mice against the lethal effect of LPS when given at the same time as LPS challenge, but it failed to protect mice when delayed 15 min after LPS challenge. The same preparation was also effective after challenge with lipid A but not after challenge with Staphylococcus aureus enterotoxin. The protection was correlated with a strong decrease of circulating tumor necrosis factor. These data demonstrate that in vivo LBP is a major mediator of the lethal effects of endotoxemia.