A comparison of CO2 laser versus traditional stapedectomy outcomes.

The aim of this study was to audit the introduction of the use of the CO2 laser into our department and to compare hearing outcomes and complication rates in patients who underwent either laser or mechanical stapedectomy. We found that the use of laser is at least as safe as the traditional approach with regards the rate of post-operative complications. One patient in the laser group suffered prolonged post-operative tinnitus, whilst one patient in the traditional group suffered prolonged post-operative vertigo. There was no evidence, however, of improved Air-Bone Gap closure compared to the traditional approach (Pre- and Post-Op Air Bone Gaps of 34 +/- 3 and 9 +/- 2 for laser stapedectomy versus 35 +/- 4 and 13 +/- 2 for traditional stapedectomy (mean +/- SEM)). In summary, therefore, CO2 laser surgery for otosclerosis is a safe surgical procedure resulting in similar hearing outcomes to that obtained following mechanical stapes surgery.

Up front about frontal headaches and sinusitis.

In clinical practice frontal headaches are common however are frequently incorrectly attributed to rhinosinusitis. The misdiagnosis of frontal headaches and/or facial pain has been compounded by increased accessibility and over-reliance on sinus CT imaging. We reviewed the presentation and clinical findings of 3 patients in our unit with frontal headaches misattributed to rhinosinusitis. We also reviewed the literature regarding the diagnostic criterias for rhinosinusitis and the role/limitations of CT imaging in the diagnosis of paranasal sinus disease. All 3 patients had isolated frontal headaches in association with normal nasal examination. They had also undergone CT imaging with isolated frontal sinus opacification evident in 2 cases and frontal and maxillary opacification in the third. All failed medical therapy and when CT imaging was repeated, it was found to be normal. The combination of facial pain/headache alone and sinus opacification on CT imaging do not meet the criteria for either acute rhinosinusitis or chronic rhinosinusitis. Other symptomotolgy, CT and endoscopic findings need to be considered to prevent the incorrect diagnosis of rhinosinusitis and unnecessary surgical intervention. For those cases where the clinical presentation does not support a diagnosis of rhinosinusitis, repeat CT imaging and a neurology consultation may help in clarifying the diagnosis and deciding which patients really do need surgery.

Platelet-delivered factor VIII provides limited resistance to anti-factor VIII inhibitors.

BACKGROUND: Gene therapy strategies directed at expressing factor (F)VIII in megakaryocytes has potential advantages in the treatment of hemophilia A. Among these is that platelet (p) FVIII may be effective in the presence of circulating anti-FVIII inhibitors. OBJECTIVE: We examined in a murine transgenic model whether pFVIII could correct the coagulation defect in FVIII(null) mouse in the presence of circulating inhibitors. METHODS: FVIII(null) mice that were transgenic for pFVIII (pFVIII/FVIII(null)) were compared with FVIII(null) mice receiving infused FVIII in a FeCl(3) carotid injury model in the presence of anti-FVIII inhibitors. RESULTS: After injury, pFVIII/FVIII(null) mice were significantly more resistant to circulating inhibitors than after plasma FVIII correction in both an acute and chronic models of inhibitor exposure even although in the chronic model, significant amounts of inhibitor were stored within the platelets. Furthermore, bleeding in the pFVIII mice in the presence of inhibitors was not as a result of the development of thrombocytopenia. CONCLUSION: In FVIII(null) mice, pFVIII provides improved, but limited, protection in the presence of inhibitors of approximately 6-fold greater Bethesda Units per mL relative to infused FVIII. Our findings differ from a recent report using a tail-clip exsanguination assay on the degree of efficacy of pFVIII in the presence of inhibitors. We propose that this difference in outcome is as a result of the sensitivity of the tail-vein exsanguination model to low levels of pFVIII.

How we did it: neopharyngeal stricture management with the nitinol stent in the laryngectomized patient: our disappointing results.

Serial dilatation, the mainstay of benign 'neopharyngeal' stricture management, can have inconsistent results. Nitinol stents, as a metallic self-expanding coil, may have a role in such patients. Such stents were inserted in four patients but two had to be removed because of intractable pain. It is concluded that nitinol stents are unlikely to have a significant role in the management of neopharyngeal stricture management.

The changing face of lateral sinus thrombosis.

Lateral sinus thrombosis is a life threatening complication of middle ear disease, the presentation, diagnosis and management of which has seen many changes in recent times. While the introduction of antibiotics has been associated with a reduction in the incidence and associated morbidity/mortality of this complication, their use has also altered the clinical features of presentation, consequently diagnosis requires a high index of suspicion. Radiological advances, in particular magnetic resonance imaging and magnetic resonance venography, have improved our ability to diagnose this complication pre-operatively, and now are the diagnostic investigations of choice. Intraoperative sigmoid sinus exploration and removal of all necrotic clot are essential steps of surgical management together with appropriate antimicrobial treatment, however the role of anticoagulation therapy remains controversial. We present four recent cases of sigmoid sinus thrombosis and discuss the clinical presentation, investigation and management of this disease.

Posterior epistaxis: identification of common bleeding sites.

OBJECTIVE: The objective of this study was to determine common bleeding sites in the nasal cavity of patients with posterior epistaxis and thus review our management protocol. STUDY DESIGN: A prospective study was carried out from 1989 to November 2003 in the otolaryngology-head and neck surgery department of a tertiary referral center. This study included patients who presented with posterior epistaxis uncontrolled with standard nasal packing and with no identifiable bleeding point on examination under local anesthesia. METHOD: All patients underwent a formal examination under general anesthesia by the senior author of this article. Findings at examination were documented along with subsequent management and its outcome. RESULTS: Forty-three patients were included in this study. Bleeding points were identified in 36 cases. Seven patients had septal bleeding points (20%). The rest were located on the lateral nasal wall (81%). Of these, 4 were on the lateral wall of inferior meatus, 7 on the lateral surface of inferior turbinate, 8 on the lateral wall of middle meatus, and 10 on the lateral surface of middle turbinate. All were located posteriorly. CONCLUSIONS: We recommend examination under general anesthesia when conservative measures fail to control bleeding, concentrating on the posterior aspect of the lateral nasal wall. In addition, the lateral aspect of the middle and inferior turbinates may contain a groove within which bleeding points may be concealed. The lateral position of most bleeding sites indicates that use of nasal packing can only attempt to indirectly tamponade blood flow and is rarely justified bilaterally. Electrothermocautery can achieve excellent results with minimal complications. Failure to identify a bleeding point, after thorough examination under general anesthesia, does not require further intervention unless complicated by further bleeding.

An alternative technique for nasal biopsy.

OBJECTIVES/HYPOTHESIS: The objective was to investigate the effectiveness of co-phenylcaine as a topical anesthetic agent for nasal mucosal biopsy. STUDY DESIGN: A prospective study. METHODS: Nasal mucosal biopsy specimens were taken from a site just anterior to the inferior turbinate following topical anesthesia with co-phenylcaine. All volunteers graded pain according to standard visual analogue scale (0-10) (VAS) scoring, and all were followed up after 24 hours for any epistaxis. RESULTS: Ninety nasal biopsy specimens were removed from 41 patients in all. Eight-two percent did not report any discomfort following this procedure (VAS score, 0). Ten patients reported mild discomfort (VAS scores ranging between, 1 and 3) and only six reported pain (VAS scores ranging from 5 to 7). However, five of these patients agreed to further biopsy and documented no discomfort during the repeat procedure. Only one patient required immediate intervention for hemorrhage after the procedure. In cases in which bleeding occurred (seven patients) it was documented within the first 6 hours, was minimal in content, and was controlled with local pressure. No systemic side effects were experienced. CONCLUSION: Co-phenylcaine is a suitable topical anesthetic agent for nasal mucosal biopsy. Removal of nasal tissue from a site anterior to the inferior turbinate can be performed under direct vision and provides sufficient tissue for histological assessment.

Localization of distal regulatory domains in the megakaryocyte-specific platelet basic protein/platelet factor 4 gene locus.

The genes for the related human (h) chemokines, PBP (platelet basic protein) and PF4 (platelet factor 4), are within 5.3 kilobases (kb) of each other and form a megakaryocyte-specific gene locus. The hypothesis was considered that the PBP and PF4 genes share a common distal regulatory region(s) that leads to their high-level megakaryocyte-specific expression in vivo. This study examined PBP and PF4 expression in transgenic mice using 4 distinct human PBP/PF4 gene locus constructs. These studies showed that within the region studied there was sufficient information to regulate tissue-specific expression of both hPBP and hPF4. Indeed this region contained sufficient DNA information to lead to expression levels of PBP and PF4 comparable to the homologous mouse genes in a position-independent, copy number-dependent fashion. These studies also indicated that the DNA domains that led to this expression were distinct for the 2 genes; hPBP expression is regulated by a region that is 1.5 to 4.4 kb upstream of that gene. Expression of hPF4 is regulated by a region that is either intergenic between the 2 genes or immediately downstream of the hPF4 gene. Comparison of the available human and mouse sequences shows conserved flanking region domains containing potential megakaryocyte-related transcriptional factor DNA-binding sites. Further analysis of these regulatory regions may identify enhancer domains involved in megakaryopoiesis that may be useful in the selective expression of other genes in megakaryocytes and platelets as a strategy for regulating hemostasis, thrombosis, and inflammation. (Blood. 2001;98:610-617)

Neural fibrolipoma: an unusual case.

A 45-year-old gentleman presented with a diffuse left neck mass. Surgical exploration revealed a large lipomatous lesion. Histological examination identified this to be a neural fibrolipoma. This is the first reported case of this lesion in the neck.

Characterization of the murine platelet alphaIIb gene and encoded cDNA.

The alphaIIb/beta3 receptor is central to platelet aggregation. Biological studies of this receptor have been limited by the inability to reproduce alphaIIb/beta3 function in a cell system. Increasingly, efforts are being directed at studies of this receptor in mice models. The structure of murine (m) beta3 has been reported. We now have sequenced the malphaIIb gene and found that it has the same size and organization as the human gene. The exon/intron borders are reported here, as are the distances between exons. malphaIIb protein is 1,033 amino acids (aa), 7 and 5 aa shorter than human (h) and rodent (r) alphaIIb, respectively, with 79% and 90% homology, respectively. As part of the comparative analysis of the 3 known alphaIIb chains included in this report, we found that a particular region of the alphaIIb N-terminal beta-propeller is highly conserved and speculate that it directly participates in ligand binding.

The human platelet alphaIIb gene is not closely linked to its integrin partner beta3.

alphaIIbb3 integrin is a heterodimeric receptor facilitating platelet aggregation. Both genes are on chromosome 17q21.32. Intergenic distance between them has been reported to be 125 to 260 kilobasepairs (kb) by pulsed-field gel electrophoresis (PFGE) genomic analysis, suggesting that they may be regulated coordinately during megakaryopoiesis. In contrast, other studies suggest these genes are greater than 2.0 megabasepairs (mb) apart. Because of the potential biological implications of having these two megakaryocytic-specific genes contiguous, we attempted to resolve this discrepancy. Taking advantage of large kindreds with mutations in either alphaIIb or beta3, we have developed a genetic linkage map between the thyroid receptor hormone-1 gene (THRA1) and beta3 as follows: cen-THRA1-BRCA1-D17S579/alphaIIb-beta3-qte r, with a distance of 1.3 centiMorgans (cM) between alphaIIb and beta3 and the two genes being oriented in the same direction. PFGE genomic and YAC clone analysis showed that the beta3 gene is distal and >/=365 kb upstream of alphaIIb. Additional restriction mapping shows alphaIIb is linked to the erythrocyte band 3 (EPB3) gene, and beta3 to the homeobox HOX2b gene. Analysis of alphaIIb(+)-BAC and P1 clones confirm that the EPB3 gene is approximately 110 kb downstream of the alphaIIb gene. Sequencing the region surrounding the human alphaIIb locus showed the Granulin gene approximately 18 kb downstream to alphaIIb, and the KIAA0553 gene approximately 5.7 kb upstream. This organization is conserved in the murine sequence. These studies show that alphaIIb and beta3 are not closely linked, with alphaIIb flanked by nonmegakaryocytic genes, and imply that they are unlikely to share common regulatory domains during megakaryopoiesis.

In vitro expansion of megakaryocytes from peripheral blood hematopoietic progenitors.

Recently, there have been several reports describing the in vitro proliferation and differentiation of megakaryocytic progenitor cells, isolated from either bone marrow (BM) or peripheral blood (PB), into relatively pure human mega-karyocytes (1,2). These culture systems originated from the discovery that Ficoll isolated human mononuclear PB cells, when stimulated with aplastic sera from thrombocytopenic animals, differentiated into megakaryocytes (3), and also from the finding that the megakaryocyte progenitors found in PB or BM typically express the CD34 antigen on their cell surface (4). Collectively, these two discoveries led to a system whereby PB isolated CD34(+) cells are cultured with an exogenously derived cytokine soup of growth and differentiation factors. Finally, after a variable expansion period, from 8-14 d, the cells are analyzed for megakaryocytic antigenic markers, such as αIIb/ß3 (CD41). The disadvantage of this system is that it is a short-term one, with most of these primary cells being dead 21 d after their initial plating. Other "long-term" systems where the developing CD34(+) cells are grown in the presence of cytokine expressing human BM microvascular endothelial cells have demonstrated 200-fold expansions over a 2-month growth period (5). Both the short- and long-term culture systems have the potential to generate sufficient numbers of megakaryocytes for doing transient or stable expression studies or for other applications, such as providing sufficient megakaryocyte nuclear extracts for electrophoretic mobility shift assays or nuclei for DNase1 hypersensitivity studies.

Three-dimensional stress analysis of polypropylene leaflets for prosthetic heart valves.

The effect of changing the modulus and thickness of the material in the leaflets of an artificial heart valve has been investigated. This has been achieved with a finite element model of the valve having approximately 2300 thin shell elements. The valve motion and the resulting stresses are modelled dynamically during closure, and subsequent pressurisation. The stresses decrease as the leaflets are made thicker and the modulus is increased. Local and global thickening has been investigated. The highest stresses appear at the tops of the stent posts in the regions of the commissures. When the modulus is too low, or the leaflets are too thin, the valve prolapsed.

A comparative study of linear and nonlinear simulations of the leaflets in a bioprosthetic heart valve during the cardiac cycle.

Two geometrically identical models of the leaflets of a bicuspid bioprosthetic heart valve have been constructed using finite elements. The boundary conditions applied to the models were also identical but a linear material model has been used in one and a nonlinear elastic model in the other. The models were fullscale and contained 2600 Belytschko-Lin-Tsai shell elements which allowed the variation of stress through the thickness of the leaflet to be modelled. A time-varying, spatially-uniform pressure differential was applied across the leaflets to model their behaviour during a complete cardiac cycle. The simulation was performed using a dynamic, explicit, time-stepping, finite element code. A comparison of the two models showed that the nonlinear model was more responsive to the time-varying pressure wave, and deformed into more complex shapes during the opening and closing phases which induced lower compressive but higher tensile stresses in the leaflets.

Brief intermittent reperfusion during renal ischemia: effects on adenine nucleotides, oxidant stress, and the severity of renal failure.

The purpose of this study was to assess how brief periods of intermittent reperfusion (IR) imposed during a renal ischemic insult affect adenine nucleotide/catabolite concentrations, oxidant stress, and the severity of ischemic acute renal failure (IARF). Rats were subjected to 35 minutes of renal pedicle occlusion with or without brief IR periods (total less than or equal to 3 minutes). Adenine nucleotides and their catabolites were measured at the end of ischemia and at 30 minutes of the recovery period. Oxidant stress in the recovery phase was assessed by non-protein-bound sulfhydryl and malondialdehyde (MDA) concentrations. The severity of IARF was quantified at 24 hours by degrees of azotemia and histologic damage. Although IR had no significant impact on end-ischemic ATP concentrations, it did induce profound adenine nucleotide catabolite depletion; the sum of adenosine, inosine, inosine monophosphate, hypoxanthine, and xanthine fell by 78%, compared with control ischemia values (p less than 0.001). The pattern of IR affected the degree of catabolite depletion: dividing a single 3-minute IR period into two 1 1/2-minute segments increased catabolite loss by 45% without affecting adenine nucleotide content. Although adenine nucleotide catabolites can be resynthesized to ATP, IR did not worsen postischemic adenine nucleotide recovery. IR augmented postischemic sulfhydryl depletion by 8% (p less than 0.02). However, lipid peroxidation (as assessed by MDA) did not result and the severity of IARF was not adversely affected.(ABSTRACT TRUNCATED AT 250 WORDS)

An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury.

Previous studies indicated that administration of a monoclonal antibody (MoAb 60.3), which blocks neutrophil adherence to rabbit endothelial cells, prevents ischemic-reperfusion (I-R) injury in multiple extrarenal organs. These findings indicated that the neutrophil can be a critical mediator of I-R tissue damage. To assess whether the neutrophil affects renal I-R injury, MoAb 60.3 was given to rabbits that were then subjected to either 50 minutes or 38 minutes of renal ischemia induced by renal artery occlusion (RAO). The severity of kidney damage was assessed 24 and 48 hours later by blood urea nitrogen and plasma creatinine concentrations and by renal histology. The results were compared with those obtained in time-matched RAO controls. MoAb 60.3 conferred no functional or morphologic protection against either severe or mild ischemic insults. To further evaluate whether neutrophils affect renal I-R injury, rats were depleted of neutrophils (less than 200 cells/mm3) by anti-neutrophil serum administration and then they were subjected to either 37 minutes or 29 minutes of RAO. Neutrophil depletion conferred neither functional nor morphologic protection when compared with time-matched RAO controls. It was concluded that the uniform lack of protection noted in these experiments, despite that two different animals, two different ways of interfering with neutrophil function, and differing severities of ischemic injury were studied, strongly suggests that the neutrophil is not a critical participant in the renal I-R injury process.

Coumadin and aspirin in prevention of recurrence after transluminal coronary angioplasty: a randomized study.

To determine the influence of adjunctive treatment with coumadin or aspirin on recurrence rate after percutaneous transluminal coronary angioplasty (PTCA), 248 patients in whom PTCA was assessed to be a primary success were randomized to either 325 mm aspirin daily or to coumadin treatment sufficient to maintain a prothrombin time 2 to 2.5 times the control value. The follow-up protocol included stress testing and coronary angiographic examinations 3 to 6 months after PTCA. All patients were followed for at least 9 months. Of the 122 patients randomized to coumadin 44 (36%) had recurrent stenoses as opposed to 34/126 (27%) of patients on aspirin, a difference that did not reach statistical significance at the .05 level. However, patients with at least a 6 month history of angina demonstrated a significantly different response to adjunctive treatment in that 19/43 (44%) of coumadin patients as compared with 10/48 (21%) of aspirin patients had recurrent stenoses (p less than .05). Thus, coumadin was not shown to be more effective than aspirin as adjunctive treatment after PTCA, while aspirin was shown to be superior to coumadin in patients with a longer history of angina.