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PubMed1998

The diagnostic usefulness of bone marrow cultures in patients with fever of unknown origin.

Bone marrow cultures (BMCs) and blood cultures (BCs) are frequently obtained in the evaluation of fever of unknown origin (FUO). However, the low yield of clinically significant isolates leads to questions about their cost-effectiveness. We retrospectively compared BMC with BC and studied the usefulness of bone marrow trephine biopsy (BMTB) histopathology in detecting infection in an unselected population of 61 patients with FUO, among whom 215 BMCs had been performed. For patients who had undergone BMTB, the histopathology was evaluated for granulomas and microorganisms. Only 1 BMC had a clinically significant isolate, Mycobacterium avium complex (MAC), which was also identified by BC. Rhodotorula rubra was found in the BMC of another patient and classified as a contaminant. Both patients had HIV infection. No growth occurred in BCs for the other 59 patients. Culture results for all 26 BMTB specimens were negative; 4 contained nonnecrotizing granulomas, including the case with MAC. BMCs are probably not justified for routine initial evaluation of FUO, but may be valuable after culture results for blood and easily obtainable tissues have been negative. Bone marrow histopathology and special stains for microorganisms in the absence of granulomas were noncontributory.

Acquired Immunodeficiency Syndrome↗
PubMed1976

Oxalosis. An unusual cause of myelophthisis in childhood.

In a child with renal failure and oliguria due to hyperoxaluria myelophthisis developed as a result of extensive bone-marrow replacement with calcium oxalate crystals and an accompanying fibrous proliferations. The histopathology associated with this metabolic disorder was demonstrated in posterior iliac crest bone-marrow trephine biopsies, renal biopsies, and nephrectomy specimens. Crystals were demonstrated in biopsy specimens of transplanted kidneys within six weeks following renal transplantation.

Anemia, Myelophthisic↗
PubMed1984

Transformation of chronic myelogenous leukemia: clinical, morphologic, and cytogenetic features.

The morphologic, cytogenetic, and clinical features of 58 patients with transformation of Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) were evaluated. The patients were divided into two groups on the basis of blood and marrow findings: blast crisis and subacute transformation. The evolution of the leukemic process in 41 patients was classified as blast crisis based on one of three criteria: 30% or more blasts in blood and/or marrow smears, intramedullary focus of blast transformation in a marrow trephine biopsy, or blast transformation in an extramedullary site. The 17 patients with subacute transformation of CML had a deteriorating clinical and hematologic picture but did not manifest any of the criteria for blast crisis. The blood and marrow findings in this group of patients were characterized by several qualitative and quantitative changes, including anemia, thrombocytopenia, decreasing leukocyte count, increasing basophilia, myelofibrosis, dysplastic alterations in hematopoietic cells, and increased blasts which, however, never exceeded 25%. Chromosome abnormalities in addition to the Ph1 were found in 65% of the patients with blast crisis and 86% of the patients with subacute transformation. The 41 patients with blast crisis had a median survival of nine weeks; the 17 with subacute transformation had a median survival of 26 weeks. The shortest median survival for patients with blast crisis, four weeks, occurred in the patients with myeloid blast crisis with chromosome abnormalities in addition to the Ph. The longest median survival, 52 plus weeks, occurred in patients with lymphoid blast crisis with only the Ph1 at transformation.

Bone Marrow↗
PubMed1985

The differential diagnosis of hairy cell leukemia with a panel of monoclonal antibodies.

A panel of monoclonal antibodies reactive with normal human lymphoid cells and with hairy cells has been applied to the immunocytochemical analysis of hairy cell leukemia. Staining was performed by immunoenzymatic methods on frozen sections of bone marrow trephines and extramedullary tissues and on cell smears. Hairy cells reacted with antibodies against HLA-DR, leukocyte common antigen, B-cell antigens (antibodies To15 and B1) and with three anti-hairy cell monoclonal antibodies (S-HCL3, HC1, and HC2). Neoplastic cells in other B-cell lymphoproliferative disorders also expressed HLA-DR, leukocyte common, and B-cell antigens but were consistently negative for the antigen detected by monoclonal antibody S-HCL3. Furthermore, hairy cells differed from other neoplastic B-cells in that they were unreactive with monoclonal antibodies against C3b receptors, anti-Leu-1, Tü1, Tü33, and lacked a meshwork of dendritic reticulum cells. These findings establish a distinctive antigenic phenotype for hairy cell leukemia and indicate that it may be diagnosed reliably by immunoenzymatic labeling of tissue sections or cell smears.

Acute Disease↗
PubMed1986

Bone marrow manifestations of peripheral T-cell lymphoma. A study of 30 cases.

Morphologic and clinical features of 30 patients with peripheral T-cell lymphoma (PTCL) were studied with particular attention to bone marrow and blood manifestations. Twenty-four (80%) patients had marrow involvement with lymphoma in trephine biopsies at initial diagnosis; two other patients subsequently developed marrow involvement. The bone marrow lesions were diffuse in 58% of the cases and focal, nonparatrabecular in 42%. A morphologic spectrum of lymphoma cells was seen with cases classified into small cell, mixed cell, and large cell/immunoblastic lymphoma. The bone marrow lesions were characterized by a heteromorphous population of lymphocytes, prominent vascularity with endothelial cell proliferation, reticulin fibrosis, and a polycellular infiltrate composed of plasma cells, eosinophils, and histiocytes. The histopathologic features in bone marrow biopsies were not pathognomonic for PTCL; the differential diagnosis may include non-Hodgkin's lymphomas of B-cell type, polymorphous reactive lymphoid lesions, including those from patients with acquired immune deficiency syndrome (AIDS), angioimmunoblastic lymphadenopathy, Hodgkin's disease, and systemic mastocytosis. The patients ranged in age from 13 to 81 years (median, 61 years) and generally presented with constitutional symptoms, lymphadenopathy, and hepatosplenomegaly. Abnormalities in one or more hematologic parameters were common and, in general, related to the degree of bone marrow involvement. Hypocalcemia was found in 40% of the patients studied and hypercalcemia in 4%. The median survival for PTCL patients was 11 months. Patients with small cell lymphoma, large cell/immunoblastic lymphoma, and marked eosinophilia had the shortest median survivals.

Adolescent↗
PubMed1987

Histopathology of myelodysplastic syndromes. The FAB classification (proposals) applied to bone marrow biopsy.

Twenty-eight cases of myelodysplastic syndrome (MDS) were reviewed to evaluate whether the morphologic criteria proposed by the French-American-British (FAB) Cooperative Group for marrow smears could be applied to glycol methacrylate embedded trephine biopsies. Bone marrow biopsies and marrow smears were examined separately and then compared for the following parameters: percentage of blasts, dyserythropoiesis, ring sideroblasts, dysmegakaryopoiesis, dysgranulopoiesis, monocytes, cellularity, fibrosis, and "abnormal localization of immature precursors". The results of the histologic (biopsies) and cytologic (marrow smears) examinations were in good agreement in 24 of 28 cases. The authors' results suggest that the five MDS types proposed by the FAB group can be reliably distinguished on bone marrow biopsy with knowledge of the peripheral blood blast and monocyte counts. When the bone marrow aspiration is inadequate, the biopsy can establish diagnosis and type of MDS and rules out aplasia or tumor infiltration as possible alternative causes of cytopenia.

Adult↗
PubMed1987

Hematologic and iron-related measurements in rheumatoid arthritis.

The hematologic status of 265 patients with rheumatoid arthritis was assessed. In the group as a whole, a mild depression in the hemoglobin concentration and mean cell volume (MCV) was associated with an increase in the red blood cell distribution width (RDW), erythrocyte sedimentation rate (ESR), and platelet count. Bone marrow trephine biopsies and further measurements of iron status and disease activity were done in [a further] 38 more anemic patients, and the findings in those with absent marrow iron (iron deficiency) were compared with those having stainable stores (anemia of chronic disorders). The RDW was raised in both, and there was no significant difference between the two groups. The concentrations of nonheme iron in the marrow and of serum ferritin were significantly lower in the iron-deficient group, but the geometric mean serum ferritin of 34 micrograms/L was still a good deal higher than that associated with uncomplicated iron deficiency. This was presumably because of the fact that the serum ferritin, which was significantly correlated with the ESR (r 0.55; P less than 0.0004) and C-reactive protein (CRP) r 0.41; P less than 0.01), was also functioning as an acute phase protein. While there was a weak correlation (r 0.37; P less than 0.04) between the marrow nonheme iron and the serum ferritin concentrations, it disappeared when nonactive patients with normal CRP concentrations were excluded. The absence of a correlation is unlike the findings that have previously been noted in other chronic inflammatory conditions and in neoplasia. This raises the possibility that serum ferritin concentrations in rheumatoid arthritis may reflect, in part at least, another store of iron located in affected joints.

Anemia↗
PubMed1988

Marrow fibrosis and multiple myeloma.

A retrospective review of pretreatment bone marrow material from 297 patients diagnosed and treated for multiple myeloma (MM) at a single institution during a 22-year period (1961-1982) was performed in order to assess the frequency and significance of associated simple marrow fibrosis (SMF). The presence of SMF was suspected in the hematoxylin and eosin-stained sections in 48 of the 297 cases and was confirmed by reticulin stains in 26 (8.8%) cases, with seven of these also showing collagen on trichrome stain. However, the literature on MM documents little recognition of this association. SMF is often responsible for inadequate marrow aspirates yielding spurious or inconclusive results. Thus, bone marrow trephine biopsies may be required to histologically confirm the diagnosis of MM when there is concurrent SMF.

Adult↗
PubMed1993

Investigation of bone marrow lymphocyte subsets in normal, reactive, and neoplastic states using paraffin-embedded biopsy specimens.

Bone marrow lymphocyte subsets in normal and reactive states and in neoplastic diseases involving the marrow were investigated with a select panel of monoclonal antibodies reactive on routinely processed, paraffin-embedded trephine biopsy material. In all cases, the antibodies beta F1 and UCHL1 (CD45RO) stained virtually equal numbers of T cells (reactive and neoplastic), whereas antibody OPD4 stained only about one half of this number of T cells. Antibody L26 (CD20) stained B cells (reactive and neoplastic) in all specimens. The T-cell to B-cell ratio in the normal marrow was between 4:1 and 5:1, and a significant increase in T-cell numbers was observed in reactive and myelodysplastic states. A significant increase in B-cell numbers, however, was seen only in marrow infiltrated by B-cell lymphoma. Bone marrow exhibiting infiltrates of B-cell lymphoma, acute leukemia, or myeloproliferative disorders showed normal or decreased numbers of T cells. These findings show that antibodies UCHL1, beta F1, and L26 can be used to determine the numbers of B and T lymphocytes in paraffin-embedded, formalin-fixed bone marrow specimens and thus may help to distinguish reactive T lymphocytosis from B-cell lymphoma.

B-Lymphocytes↗
PubMed2001

Growth hormone treatment promotes guided bone regeneration in rat calvarial defects.

This study evaluated the biomechanical strength and bone formation in calvarial critical size bone defects covered with expanded polytetrafluoroethylene (e-PTFE) membranes in rats treated systemically with recombinant human growth hormone (rhGH). A full-thickness bone defect, 5 mm in diameter, was trephined in the central part of each parietal bone in 40 one-year-old female Wistar rats, which were randomly assigned to two groups of 20 animals each. The bone defects were covered with an exocranial and an endocranial e-PTFE membrane. From the day of operation, the rhGH-treated animals were given 2.7 mg rhGH/kg/day and the placebo-injected rats were given isotonic sodium chloride. The animals were killed 28 days after operation. The biomechanical test was performed by a punch out test procedure placing a 3.5-mm diameter steel punch in the centre of the right healed defect. After mechanical testing, the newly formed tissue inside the defect was removed and the dry and ash weights were measured. The left healed defects were used for three-dimensional (3D) reconstruction by means of micro-computer tomography (micro-CT). Ultimate load, ultimate stiffness, and energy absorption at ultimate load were significantly increased in the rhGH-treated group (P < 0.003). Also, tissue dry and ash weights were significantly augmented in the rhGH-treated group (P < 0.001). The 3D reconstruction of newly formed bone showed that there was almost twice as much bone volume present in the rhGH-treated defects compared with the placebo group. The experiment demonstrated that rhGH administration enhances bone deposition and mechanical strength of healing rat calvarial defects, covered with e-PTFE membranes.

Animals↗
PubMed1991

Modelling and numerical optimization of corneal rotation.

Rotational ipsilateral penetrating autokeratoplasty can be performed for patients whose vision is impaired by corneal opacities overlying the pupil and where an adequate area of clear peripheral cornea is present. A method is presented for determining the maximum clear central corneal area that can be obtained by rotational autokeratoplasty and the most appropriate trephine size and placement. The mathematical modelling consists of estimating the shape of the opacity perimeter using nonlinear constrained optimization.

Cornea↗
PubMed1979

Ocular infection with herpes simplex virus type 1: prevention of acute herpetic encephalitis by systemic administration of virus-specific antibody.

The effects of virus-specific antibody on the pathogenesis of infection due to herpes simplex virus type 1 (HSV-1) following corneal inoculation of young adult mice were studied. HSV-1 was inoculated onto the corneal surface immediately after trephination with a capillary pipette. After inoculation, virus spread to the trigeminal ganglion and brain within two days and caused acute herpetic encephalitis, which killed infected animals eight to 10 days after infection. Rabbit hyperimmune antisera to HSV-1 were prepared, diluted to contain antibody at a titer of 1:150, and administered intraperitoneally to mice 8 hr after corneal infection. Administration of antisera did not interfere with the spread of HSV-1 from the site of infection to the trigeminal ganglion and brain but did reduce the multiplication of virus within the central nervous system. Reduction in viral replication resulted in complete recovery of the animals that were given antibody to HSV-1. however, the animals were not protected if they were irradiated with 390 rad 24 hr prior to administration of antibody. This observation suggested that antibody-mediated protection was not the result of in vivo neutralization of virus but instead required the presence of antibody as well as one or more radiation-sensitive components.

Animals↗
PubMed2001

The utility of bone-marrow examination in HIV-infected adults in South Africa.

We retrospectively reviewed a consecutive case series of 257 adults with HIV infection who had undergone a bone-marrow examination with trephine bone biopsy, to assess the diagnostic usefulness of bone-marrow examination and evaluate possible predictors of a diagnostic examination. Bone-marrow examination was positive in 97 (38%) patients and gave a unique diagnosis in 61 (24%). The diseases were tuberculosis (83 patients), Mycobacterium avium complex infection and cryptococcosis (four patients each), and haematological malignancies (eight patients). The yield of the examination was significantly increased, by univariate analysis, in patients with wasting, oral thrush, leukopenia, CD4< or =100/mm3, and granuloma formation on histopathology. Granulomata were present in 113 (44%) patients, of whom 28 (25%) had no specific cause identified. Granulomata occurred in 22 (25%) of 89 patients with CD4 >100/mm3 compared to 36 (51%) of 70 patients with CD4< or =100/mm3 (OR 0.3; 95%CI 0.15-0.62). Of 48 patients with CD4 <50/mm3, 25 had granulomata, including 15 with caseation necrosis. The yield of bone-marrow examination was considerable in our setting. Expanding access to modern blood culture techniques for mycobacteria to primary care level could limit the number of bone-marrow examinations required.

AIDS-Related Opportunistic Infections↗
PubMed1988

Sequential half-body irradiation as salvage therapy in chemotherapy-resistant multiple myeloma.

Fifteen patients with a median age of 58 years, having multiple myeloma resistant to conventional combinations of cytotoxic drugs, received sequential half-body irradiation as salvage therapy. Response was obtained in 53% (n = 8: group 1); this was objective in 40% (n = 6), being defined as 50% or greater reduction in paraprotein, clearance of light chains from the urine, or an unequivocal decrease in tumor bulk on an adequate marrow trephine biopsy; a further 13% (n = 2) just failed to meet these criteria but nevertheless had excellent subjective response. Median survival was 24 months. No objective or subjective improvement occurred in 47% (n = 7: group 2); median transient survival was 4 months. Short-term toxicity was limited to transient nausea in 30% (n = 5) and protracted pancytopenia in about one-half of the patients (n = 7), who remain dependent on intermittent RBC transfusions. Morbidity is only moderate, and the response rate of 53% in refractory patients suggests that sequential half-body irradiation has a definite place in managing patients with end-stage disseminated myelomatosis.

Adult↗
PubMed2002

Primary cutaneous follicular lymphoma: a clinicopathologic and molecular study of 16 cases in support of a distinct entity.

Primary cutaneous B-cell lymphomas displaying a prominent follicular growth pattern are rare and remain poorly defined, particularly in terms of the frequency of detection of t(14;18) and whether or not, as a group, they represent an entity distinct from follicular lymphoma arising in lymph nodes. The morphologic, immunophenotypic, and clinical features of 16 cases of primary cutaneous follicular lymphoma, identified during a review of all PCBCL in the Scotland and Newcastle Lymphoma Group database, were studied and the number of cases harboring t(14;18) assessed by polymerase chain reaction using primers to the major breakpoint cluster region. Comparisons were made with stage I follicular lymphoma arising in lymph nodes and follicular lymphoma secondarily involving the skin. All cases of primary cutaneous follicular lymphoma had undergone thorough staging, including physical examination and CT scans of chest and abdomen, with 15 of 16 cases also having bone marrow aspiration and/or trephine performed. The morphology and immunophenotype of the lesions were similar to that expected in lymph nodes. All cases displayed a follicular architecture complete with follicular dendritic cell networks and comprised an admixture of CD10 and/or bcl-6-positive neoplastic centrocytes and centroblasts with 13 of 16 cases also expressing bcl-2 protein. None harbored t(14;18), a significantly different finding compared with cases of stage I nodal follicular lymphoma (p <0.001) and secondary cutaneous follicular lymphoma (p <0.039). Relapses occurred in five of 15 patients with a median time to first relapse of 20 months (range 1-73 months; mean 27.2 months). These were multiple in two patients and involved extracutaneous sites in two patients. The propensity for relapse was similar to that in a comparative cohort of stage I nodal follicular lymphoma, but the group of primary cutaneous follicular lymphoma were significantly more likely to attain complete remission; all cases of primary cutaneous follicular lymphoma were in complete remission when last seen compared with 49 of 87 patients with stage I nodal follicular lymphoma (p <0.005). No lymphoma-related deaths were encountered in 15 cases with a mean follow-up >60 months (range 5-119 months). These results support the concept of a subtype of follicular lymphoma lacking t(14;18) involving the major breakpoint cluster region, and with a propensity to arise in the skin. Despite a high relapse rate patients with primary cutaneous follicular lymphoma are more likely to achieve complete remission and may ultimately have a more favorable long-term prognosis than those with equivalent nodal disease.

Adult↗
PubMed2000

Endoscopic intracranial craniofacial and monobloc osteotomies with the aid of a malleable high-speed pneumatic drill: a cadaveric and clinical study.

Endoscopic techniques are now an accepted part of the surgical armamentarium and are used routinely in a number of aesthetic and reconstructive procedures. Endoscopic techniques are now being used commonly by plastic surgeons in forehead and face lifts. In both craniofacial surgery and in neurosurgery, the application of endoscopy potentially allows the surgical team to perform wide dissection of the dura mater in a minimally invasive fashion, thereby potentially reducing the risk of dural and brain injury. Also reduced by this surgical approach is potential injury to the major venous structures, such as the sagittal sinus, along with overall reduced bleeding. After an extensive laboratory study of 10 cadaveric dissections, the authors have refined a new endoscopic technique for completing an endoscopic intracranial craniofacial osteotomy. This study was conducted in the Department of Pathology at the University of Brno (Czech Republic), and was performed as a cooperative multicenter project between the University of Palermo, the Albert Einstein College of Medicine/ Montefiore Medical Center, the Hospital Infantil de Mexico, "Federico Gomez," and the Medtronic Midas Rex Institute, (Fort Worth, TX). During this cadaveric anatomic study and using small trephinations and skin incisions the authors were able to develop several different craniofacial and endoscopic monobloc procedures. To accomplish intracranial and facial osteotomies, a new malleable high-speed drill was designed for use in the endoscopic craniofacial approach. Using these newly developed cadaveric techniques and instrumentation, the authors performed two intracranial craniofacial procedures on children with congenital craniofacial anomalies. There would appear to be several significant advantages for the craniofacial patient as result of these new techniques: reduced surgical trauma, operative bleeding, surgical time, and hospitalization, along with a reduced risk of infection. It became quickly apparent, as a result of these cadaveric studies, that the learning curve for this endoscopic procedure is quite steep. Tutino M, Chico F, Tutino M, Goodrich JT, Ortiz Monasterio F. Endoscopic intracranial craniofacial and monobloc osteotomies with the aid of a malleable high-speed pneumatic drill: a cadaveric and clinical study.

Aged↗
PubMed1994

Unicortical critical size defect of rabbit tibia is larger than 8 mm.

The critical-size defect is important as an experimental model to test bone repair materials. Guided tissue regeneration is an established method for tissue regeneration within periodontal surgery. Bony defects covered by a membrane are allowed to be filled by bony tissue. Healing of 8-mm unicortical trephine defects was tested in Copenhagen White rabbit tibia using 3 different membranes. The critical-size defect in Copenhagen White rabbit tibia is larger than 8 mm, because control defects 8 mm in diameter healed spontaneously. However, it is anatomically not possible to create defects larger than 8 mm in an adult Copenhagen White rabbit tibia.

Animals↗
PubMed1998

Importance of the critical-size bone defect in testing bone-regenerating materials.

A substantial interest exists in developing substitute materials and human recombinant bone-inducing factors to enhance bone regeneration both in the craniofacial complex and in other parts of the skeleton. A persistent problem has been to find an animal model that allows for the comparison of different osteopromotive materials. The purpose of this investigation was 1) to determine whether a 5-mm calvarial defect in adult rats fulfilled the requirements of a critical-size bone defect and 2) to discuss the use of this animal model in assessing bone repair in the craniofacial region. Bilateral full-thickness calvarial defects were trephined in the calvarial bone of 56 5- to 6-month-old Wistar rats. Except for minor amounts of bone formation limited to the margins of the defect, none of the defects revealed any signs of spontaneous bone regeneration 6 and 12 months after surgery. The full-thickness 5-mm calvarial defects thus fulfill the criteria for a critical-size bone defect. This animal model allows for an experiment with a paired design, it avoids inclusion of the sagittal suture in the osseous defect, and it thereby minimizes morbidity by reducing the risk of damaging the midsagittal sinus. An adequate experimental model has been developed to evaluate the efficiency of osteopromotive materials in the healing of bone defects in the craniomaxillofacial region.

Animals↗