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Histopathology of B-cell chronic lymphocytic leukemia.

Histologic and immunohistologic findings of B-cell chronic lymphocytic leukemia/small lymphocytic leukemia are revised in the light of the more recent knowledge on the pathobiology of the disease. The guidelines for the optimal handling of the bioptic samples are provided. The relevance of the examination of trephines and surgical specimens is outlined with special reference to the identification of risk factors in individual patients.

Biopsy↗

Primary diagnosis of Whipple's disease in bone marrow.

Whipple's disease (WD) is a chronic systemic inflammatory disease of infectious origin caused by Tropheryma whipplei (TW). Abdominal pain and recurrent diarrhea are usually the main symptoms leading to the suspicion of a primary bowel disease. Systemic manifestations can mimic hematologic disorders. A 49-year-old man presented with fever, weight loss, long-standing arthralgia, and diarrhea. A duodenal biopsy was unremarkable. Bone marrow histology provided no evidence of a malignant hematological disorder but revealed noncaseating granulomas. TW was detected in the bone marrow trephine by polymerase chain reaction. This is the first report to describe TW-associated granulomatous myelitis as the initially recognized organ manifestation of WD, proven at the molecular level. This observation is relevant for the differential diagnosis of patients with systemic symptoms and granulomatous diseases affecting the bone marrow, emphasizing that WD should be considered in cases of unexplained granulomatous myelitis, even when small bowel biopsy specimens are negative.

Bone Marrow↗

Myelodysplastic/myeloproliferative disease with erythropoietic hyperplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24): first description of a case.

We report on a patient fulfilling the diagnostic criteria of unclassifiable myelodysplastic/myeloproliferative diseases with prominent erythropoietic hyperplasia/dysplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24). The patient presented with B-symptoms, erythroblastemia, thrombopenia, marked eosinophilia, presence of myeloid precursors in the peripheral blood, and decreased erythropoietin level. Nodular peritrabecular polymorphous blasts, dysplastic megakaryocytes, and a diffuse argyrophilic fibrosis were detected in the trephine bone marrow biopsy. Immunohistochemically, the blasts stained positively for glycophorin C and hemoglobin A; the proliferation fraction was nearly 90% in the Ki-67 stain. Expression of the phosphorylated Janus kinase 2 was detected in almost all megakaryocytes and in isolated erythroblast islets, suggesting a probable activation of Janus kinase 2, the jak-2 gene being mapped on 9p24. Ten months after initial diagnosis, the disease progressed to frank acute erythroid leukemia. We report for the first time a myelodysplastic/myeloproliferative disease (erythroid preleukemia) accompanied by the specific chromosomal aberration t(8;9)(p23;p24), distinct histopathology, and clinical and laboratory symptoms, and progress to acute erythroid leukemia.

Biopsy↗

Tensile bond strength of different adhesive systems between bone and composite compared: an in vitro study.

INTRODUCTION: The aim was to compare tensile bond strength of three dentine adhesive systems (Excite, Clearfil New Bond, Etch & Prime 3.0) and two cyanoacrylate adhesives (Cyano Veneer, Histoacryl) to animal bone in vitro. MATERIAL AND METHODS: Specimens from five porcine mandibles (diameter 9 mm) with a total thickness of 4mm (+/-0.5mm) and a cortical layer of 1.5mm (+/-0.2mm) were prepared using trephine burs under constant water cooling and under standardized conditions. They were assigned to five experimental groups. Tensile bond strength of five different adhesive agents (Clearfil New Bond, Etch & Prime 3.0, Excite, Histoacryl and Cyano Veneer was measured 15 min after application and after light curing of a composite material (Tetric Ceram, colour A2) added thereupon using a universal testing machine. Qualitative control was performed by scanning electron microscopy, while examining loaded and unloaded specimens. RESULTS: The measured tensile bond strength was as follows: Clearfil New Bond 8.00 MPa (+/-1.36 MPa), Etch & Prime 3.0 4.05 MPa (+/-1.52 MPa), Excite 2.96 MPa (+/-1.34 MPa), Histoacryl 5.22 MPa (+/-2.00 MPa), Cyano Veneer 4.56 MPa (+/-0.76 MPa). Clearfil New Bond showed significantly higher bond strength than the other four adhesives. Scanning electron microscopy analysis of unloaded specimens showed mixed modes of fracture. As regards the loaded specimens, no tag formation as known for dentine was found. CONCLUSION: Within the limitations of an in vitro investigation it can be concluded that dentine adhesive systems might be useful for bone bonding. Tensile bond strength of the dentine adhesive systems tested on bone is comparable to that evaluated for dentine in earlier investigations.

Adhesiveness↗

Intraocular contact lens tamponade to facilitate penetrating keratoplasty in perforated corneas.

Penetrating keratoplasty in the presence of a perforated cornea is a relatively common and difficult surgical problem. In the worst scenario, there may be extrusion of ocular contents during trephination. Two cases of perforated corneas are presented in which a new technique was used to close the perforation and normalize intraocular pressure. This involves inserting a soft contact lens through a paracentesis into the anterior chamber. An ophthalmic viscosurgical device is then injected behind the contact lens, opening it, and allowing it to tamponade the perforation. This stabilizes the anterior chamber and allows a stable operating environment. This has not been described previously.

Aged↗

Excimer laser-assisted anterior lamellar keratoplasty for keratoconus, corneal problems after laser in situ keratomileusis, and corneal stromal opacities.

PURPOSE: To evaluate excimer laser-assisted anterior lamellar keratoplasty to augment thin corneas as in keratoconus (<350 microm) and corneal ectasia after laser in situ keratomileusis (LASIK) and to treat anterior stromal opacities. SETTING: Ophthalmology Department, School of Medicine, Gazi University, Ankara, Turkey. METHODS: Thirteen eyes (5 keratoconus, 3 macular dystrophies, 1 post-LASIK ectasia, 1 post-LASIK interstitial keratitis, 3 post-herpetic keratitis sequelae) of 13 patients were included in this prospective study. The treatment group was divided into corneal ectasia and stromal opacity groups. A donor stromal button approximately 350 microm thick received a 100 microm excimer laser ablation on the endothelium. The remaining cornea (epithelium, Bowman's membrane, and stroma) was punched with a 7.5 or 7.7 mm trephine. After transepithelial ablation of the host cornea to 200 mum thickness, the corneal button was sutured with interrupted 10-0 monofilament nylon. Sutures were removed between 3 months and 6 months postoperatively. Preoperative and postoperative simulated keratometric cylinders and corneal thickness values were compared using the Wilcoxon signed rank test. The postoperative spherical equivalent refraction and best spectacle-corrected visual acuity (BSCVA) between the groups were compared using the Mann-Whitney U test. RESULTS: The mean follow-up was 27.6 months +/- 8.3 (SD). All patients gained 2 lines or more of BSCVA, and no patient lost a line. The mean corneal thickness was 381.2 +/- 88.2 microm preoperatively, which significantly increased to 534.9 +/- 96.6 microm postoperatively (P < .05). The mean preoperative simulated keratometric cylinder was 7.44 +/- 7.18 diopters (D); postoperatively, it decreased to 2.61 +/- 1.73 D (P < .05). There was no significant difference in postoperative spherical equivalent refraction or BSCVA between the groups (P > .05). CONCLUSIONS: This technique presents a different modality for the treatment of keratoconus, post-LASIK corneal problems, and other corneal stromal opacities with anterior lamellar keratoplasty. Additional studies with more patients and longer follow-up will help determine the role of this technique as a substitute for penetrating keratoplasty in these patients.

Adult↗

Effect of circular keratotomy on keratoconus.

Circular keratotomy was performed in 3 eyes of 3 patients with keratoconus before planned lamellar keratoplasty. After peribulbar anesthesia, a circular 400 microm cut centered on the geometrical corneal center was made using a Hessburg-Barron 7.0 mm trephine (Altomed). The circular cut was deepened with a guarded diamond blade set at 90% of the thinnest point in the circumference and closed with a single 10-0 nylon running suture. Videokeratography revealed increased astigmatism and increased central curvature in all eyes. In 1 patient, a 0.2 improvement in best spectacle-corrected visual acuity (BSCVA) was noted, associated with overall corneal steepening. In the other 2 patients, refraction, BSCVA, and corneal profile worsened, requiring lamellar keratoplasty. Circular keratotomy increased corneal curvature and worsened keratoconus and is therefore not recommended.

Adult↗

Successful antibiotic treatment of Borreliosis associated pseudolymphomatous systemic infiltrates.

The clinical management of late stage Borreliosis can be difficult due to various associated symptoms and signs and cumbersome microbiological tests. We report a case of successful antibiotic treatment of Borreliosis-associated pseudolymphomatous infiltrates in bone marrow and lymph nodes, which were diagnosed by bone marrow trephine biopsy and positron emission tomography.

Agricultural Workers' Diseases↗

Severe persistent sciatic pain and weakness due to a gluteal artery pseudoaneurysm as a complication of bone marrow biopsy.

Complications of bone marrow trephine are thought to be uncommon. Herein, we present a case of severe debilitating sciatic nerve palsy secondary to a gluteal artery pseudoaneurysm following bone marrow biopsy. The pseudoaneurysm was treated successfully by percutaneous embolization; however, the patient remains significantly impaired with persistent painless foot drop.

Aneurysm, False↗

Minimally invasive tibial bone harvesting under intravenous sedation.

PURPOSE: Collecting high amounts of autogenous bone often results in considerable donor site morbidity. The hypothesis evaluated with this prospective study is that a modified approach for tibial bone harvesting using a minimally invasive access under local anesthesia plus sedation in an office setting compares favorably in terms of amount of bone harvested, morbidity, and patient satisfaction with more aggressive approaches previously reported. PATIENTS AND METHODS: Thirty-eight patients (18 women, 10 men) were treated using this method and followed prospectively. A medial approach to the proximal tibia was performed in all cases. A 10 mm incision gives access to an 8 mm manual trephine, which creates a bony window. Cancellous bone is released from the proximal compartment and a bone filter connected to suction allows fast removal of bone particles. Amount of bone harvested (compressed and non-compressed), surgical time, and complications were recorded. RESULTS: Mean surgical time was 14 minutes (range, 9 to 20 minutes). Volume of compressed cancellous bone ranged between 18 and 30 cc (mean, 28 cc). CONCLUSION: Tibial bone harvesting through a medial minimally invasive approach with a bone filter yields satisfactory results in terms of bone volume, surgical time, and patient satisfaction.

Adult↗

Relationship between gelatinases and bone turnover in the healing bone defect.

PURPOSE: The aim of this pilot study was to determine the relationship between gelatinase (MMP-9 and MMP-2) markers of soft tissue inflammation/turnover at the bone/soft tissue interface and bone turnover (osteocalcin [OC], pyridinoline cross-linked carboxyl-terminal telopeptide of type 1 collagen [ICTP], and bone fill) during healing of an alveolar bone defect. MATERIALS AND METHODS: Ten subjects undergoing oral surgery had a 5 x 5-mm trephine defect created on an edentulous ridge and were sampled at the bone/soft tissue interface at baseline (prior to flap reflection), 2 weeks and 12 weeks postsurgery, using a novel bone wash device. Recovered irrigants were analyzed for MMP-9 and MMP-2 by gelatin zymography, OC and ICTP with radioimmunoassays, and albumin (ALB; to normalize markers for blood content) with a sandwich enzyme-linked immunosorbent assay. Bone fill at 12 weeks was analyzed by radiographic absorptiometry. RESULTS: All markers of enzymatic activity and bone turnover varied significantly across time (P < or = .03), with bone turnover markers OC and ICTP decreasing between baseline and 2 weeks, and MMP-9 and MMP-2 increased. Measures generally returned to near baseline levels after 12 weeks. MMP-9 versus MMP-2 (r = 0.97, P < .0001) and OC versus ICTP (r = 0.38, P = .048) were correlated with each other, while MMP-9 and MMP-2 were negatively correlated with ICTP (r = -0.48, P = .011 and r = -0.62, P = .006, respectively). MMP-9 was negatively correlated with subsequent bone fill (r = -0.63, P = .07). CONCLUSIONS: Bone wash sampling showed that gelatinase activity at 2 weeks following creation of an alveolar defect appeared to decrease bone turnover and eventual bone fill, suggesting benefits for anti-MMP therapy during wound healing.

Alveolar Bone Loss↗

Up-regulation of DNA methyltransferases DNMT1, 3A, and 3B in myelodysplastic syndrome.

Analyzing bone marrow trephines from (myelodysplastic syndrome) MDS patients we show for the first time strong over-expression of the DNA methyltransferases 1, and 3A (and 3B to a much lesser extent) in the myelodysplastic syndrome FAB subtypes refractory anaemia (RA) and refractory anaemia with excess of blasts (RAEB). The increase in mRNA expression was much less pronounced in refractory anaemia with ringed sideroblasts (RARS). Classification according to the new WHO guidelines revealed distinct differences between RCMD and RARS. This elevated mRNA expression most probably contributes to the frequently found aberrant hypermethylation in MDS and might explain the promising clinical response of MDS patients treated with DNMT inhibitors.

Biopsy, Needle↗

Hairy cell leukemia (HCL) with extensive myelofibrosis responds to thalidomide.

We present a 75-year-old man who was admitted to our hospital because of splenomegaly, transfusion-dependent anemia and thrombocytopenia. The diagnosis of idiopathic myelofibrosis was suggested by the bone marrow trephine biopsy, which was hypocellular with myelofibrosis. Thalidomide was started at a daily dose of 100 mg/d and increased to 400 mg/d. Within 12 weeks, thrombocytes increased to 100.000/microl, hemoglobin normalized, lasting for about 11 months. Then, thalidomide had to be discontinued because of mild polyneuropathy. A second bone marrow biopsy showed fibrosis as well as a diffuse infiltration of the bone marrow (80%) by lymphocytes with expression of CD11c, CD19, CD20, CD103. Tartrate resistant acid phosphatase test (TRAP) was also positive. Hairy cell leukemia was diagnosed and he was administered 2-chlorodeoxyadenosine (2-CDA) achieving a complete remission.

Aged↗

Hemicraniectomy and durotomy for malignant middle cerebral artery infarction.

Decompressive surgery with hemicraniectomy and durotomy for malignant MCA infarction remains a salvage procedure but can be associated with reasonable clinical outcomes in highly selected patients. This selection of patients appropriate for intervention is of the utmost importance, but exact criteria remain to be defined; older age and increased numbers of associated medical comorbidities seem to define a group of patients who would not derive long term benefit, however. The determination as to whether or not surgery is equally beneficial for dominant or nondominant hemispheric infarction is hampered by lack of good comparative data, but selected case series suggest that some patients who have dominant hemispheric infarction achieve a reasonable degree of independence. Although a well-defined principle of stroke practice is that "time is brain," there are no clear data as to when intervention should be done, as there are some patients who have large MCA infarction and who may not progress to cerebral herniation. Clinicians managing the growing population of patient status post hemicraniectomy should also be aware of this process of the syndrome of the trephined and the potential for resolution that may prompt earlier cranial reconstruction. At present, the decision to proceed with this aggressive intervention of hemicraniectomy and durotomy for large ischemic infarction remains a case-by-case individualized approach, based on patient and family preferences and clinicians' subjective perspective as to patients' potential for clinical recovery.

Animals↗

Comparison of deep lamellar keratoplasty and penetrating keratoplasty in patients with keratoconus.

OBJECTIVE: To compare the therapeutic outcomes after deep lamellar keratoplasty (DLK) and penetrating keratoplasty (PK) in patients with keratoconus. DESIGN: Retrospective case-control study. PARTICIPANTS: We reviewed the clinical notes of 47 patients diagnosed clinically with keratoconus who had received DLK (26 eyes of 25 patients) or PK (25 eyes of 22 patients) at Moorfields Eye Hospital or the Royal Shrewsbury Hospital between 1994 and 2001. The patients in the 2 groups were matched for severity of their keratoconus by preoperative visual acuity. METHODS: Deep lamellar keratoplasty was performed with the Melles technique in 7 eyes and the technique described by Sugita and Kondo in 19 eyes. Penetrating keratoplasty was performed with a standard technique using a Hessburg-Barron trephine. A single continuous 16-bite 10-0 nylon suture was placed and adjusted in both groups. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), refractive results, surgical techniques for DLK, and complication rates were analyzed. RESULTS: The 25 patients with keratoconus who underwent DLK had a mean age of 32.6 years and a median follow-up of 28 months. The mean age of the 22 patients who underwent PK for keratoconus was 34 years. This group was followed up for a median time of 55 months. The median final BCVA of patients in the DLK group was 6/9 and in the PK group 6/6 (no statistical significance). The median result for the final spherical equivalent power in both groups was mild myopia, although the DLK group had more myopia, and the median astigmatism was less than 5.00 diopters cylinder for both groups. Complication rates were similar for DLK and PK, although the nature of the complications varied. CONCLUSIONS: Penetrating keratoplasty is no longer an automatic choice for the surgical treatment for keratoconus; DLK seems to be a safe alternative. Best-corrected visual acuity, refractive results, and complication rates are similar after DLK and PK. Deep lamellar keratoplasty is more technically challenging but allows the risk of endothelial rejection to be avoided and may reduce the risk of late endothelial failure.

Adolescent↗

Stability of vision, topography, and endothelial cell density from 1 year to 2 years after deep lamellar endothelial keratoplasty surgery.

PURPOSE: To evaluate whether the visual, topographic, and endothelial cell count results observed 1 year after deep lamellar endothelial keratoplasty (DLEK) surgery remain stable up to 2 years after surgery. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Twenty eyes of 20 patients with corneal edema from Fuchs' endothelial dystrophy. METHODS: Deep lamellar endothelial keratoplasty endothelial replacement surgery, with a 9.0-mm or 9.5-mm scleral access incision and a specialized intrastromal trephine, was performed. Snellen visual acuities, corneal topography, and endothelial cell counts were prospectively measured preoperatively and 1 year and 2 years after DLEK. MAIN OUTCOME MEASURES: Uncorrected and best spectacle-corrected visual acuity (BSCVA), refractive and topographic astigmatism, mean corneal curvature, topographic regularity and symmetry, and endothelial cell density. RESULTS: At 1 year postoperatively, BSCVA averaged 20/50 (range, 20/25-20/200), spherical equivalents (SE) averaged -0.194+/-1.521 diopters (D), manifest refraction (MR) astigmatism averaged 2.04+/-1.05 D (range, 0.0-4.0 D), topographic astigmatism averaged 2.3+/-1.1 D, mean corneal curvature was 43.2+/-1.8 D, the surface regularity index (SRI) averaged 1.16+/-0.41, and the surface asymmetry index (SAI) averaged 1.05+/-1.09. At 2 years postoperatively, BSCVA averaged 20/48 (range, 20/25-20/200), SE averaged -0.369+/-1.267 D, MR astigmatism averaged 1.76+/-0.66 D (range, 0.75-3.0 D), topographic astigmatism averaged 2.4+/-1.1 D, mean corneal curvature was 43.6+/-1.8 D, the SRI averaged 1.13+/-0.44, and the SAI averaged 0.76+/-0.59. There was no significant change in visual or topographic parameters between 1 year and 2 years postoperatively (P>0.05). Endothelial cell counts averaged 2335+/-468 cells/mm(2) at 1 year and 2151+/-457 cells/mm(2) at 2 years postoperatively (P = 0.041). CONCLUSIONS: Deep lamellar endothelial keratoplasty provides stable refractions, corneal topography, and endothelial cell densities as long as 2 years after surgery. The absence of corneal sutures in this technique seems to prevent the sutures in/sutures out changes in SE refractions and corneal topography sometimes seen after penetrating keratoplasty (PK). Deep lamellar endothelial keratoplasty is, therefore, an excellent alternative to PK for patients with endothelial dystrophies.

Aged↗

Compressive C-shaped lamellar keratoplasty: a surgical alternative for the management of severe astigmatism from peripheral corneal degeneration.

OBJECTIVE: To describe a compressive lamellar surgical technique for treating severe astigmatism in peripheral corneal ectasia. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Four eyes of 3 patients with either pellucid or Terrien's marginal corneal degeneration were included in this series. METHODS: C-shaped lamellar keratoplasty using multiple trephines of different sizes, with deliberate undersizing of the donor graft for a controlled compressive effect, was performed on these patients. MAIN OUTCOME MEASURES: Visual acuity outcome and refraction were measured at different intervals at up to 40 months of follow-up. RESULTS: All eyes achieved Snellen visual acuity of 20/40 or better and stable astigmatism ranging from 0 to -2.75 diopter cylinder within 6 months, with no recurrence of corneal thinning or peripheral corneal vascularization. CONCLUSIONS: Compressive C-shaped lamellar keratoplasty is able to reduce severe corneal astigmatism in peripheral corneal ectasia and can result in good visual and refractive outcomes with early visual rehabilitation.

Astigmatism↗

Anterior vitreous tapping to manage positive vitreous pressure during triple procedures.

PURPOSE: To describe the technique and outcome of pars plana vitreous aspiration during penetrating keratoplasty (PK) combined with cataract extraction (CE) and intraocular lens (IOL) implantation (triple procedure) to prevent positive vitreous pressure and its associated complications. DESIGN: Nonrandomized prospective noncomparative interventional case series. PARTICIPANTS: Sixty-five patients who underwent triple procedures between June 2001 and September 2003. METHODS: Triple procedures performed on all 65 patients consisted of PK, extracapsular CE, and IOL implantation with standard techniques. After nonpenetrating trephination, anterior vitreous tapping was performed with a 23-gauge needle on a 5-ml syringe over the pars plana 3.5 mm posterior to the limbus in the superotemporal quadrant. MAIN OUTCOME MEASURES: Preoperative best-corrected visual acuity (BCVA), volume of aspirated liquefied vitreous, intraoperative and postoperative complications, and postoperative BCVA at 3 and 6 months. RESULTS: Corneal scarring with cataract was the most common indication for surgery. Preoperative BCVA ranged from 20/160 to light perception. Aspirated vitreous volume varied from 0.3 to 1.5 ml, averaging 1.0 ml. No case had evidence of positive vitreous pressure during surgery. The mean follow-up period was 9.6+/-2.6 months (range, 6-24). Postoperative complications consisted of graft rejection in 4 cases (6.2%), primary graft failure in 3 (4.6%), and secondary glaucoma in 1 (1.5%). Of the patients, 70.8% had a postoperative BCVA of > or =20/160 at 6 months. Vitreous hemorrhage, retinal tearing, and detachment were not observed. CONCLUSIONS: Pars plana anterior vitreous tapping is a safe adjunct for triple procedures to prevent positive vitreous pressure and its associated complications.

Adult↗