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Disseminated Mycobacterium avium-intracellulare infection and red cell hypoplasia in patients with the acquired immune deficiency syndrome.

During a period of 14 months in 1985 and 1986, infection with Mycobacterium avium-intracellulare (MAI) complex was diagnosed in 10 of 76 patients with Human Immunodeficiency Virus (HIV)-associated infection. In eight of the 10 patients, the infection was disseminated. All eight patients were anaemic. A bone marrow aspirate and/or trephine biopsy performed in six of them revealed evidence of red cell hypoplasia. MAI was cultured from all six samples of bone marrow. The strains of MAI isolated were resistant to conventional antituberculous drugs but were susceptible in vitro to ansamycin, ethionamide and cycloserine. None of the eight patients responded clinically to antituberculous therapy. The eight anaemic patients had pronounced constitutional symptoms. We suggest that severe anaemia and constitutional symptoms in patients with HIV-associated disease should prompt a search for evidence of disseminated MAI infection.

Acquired Immunodeficiency Syndrome↗

Massive hepatosplenomegaly, jaundice and pancytopenia in miliary tuberculosis.

A 29-year-old Caucasian woman presented to hospital with a 2-day history of diarrhoea, anorexia and rigors. Investigations showed abnormal liver function tests, hyponatremia, hypoalbuminaemia and lymphopenia. The initial chest radiograph was normal. A bone marrow trephine biopsy showed non-caseating granulomata and she subsequently developed miliary shadowing on the chest radiograph. A transjugular liver biopsy confirmed the presence of acid-alcohol fast bacilli. Despite starting triple therapy for miliary tuberculosis she remained febrile and developed massive hepatosplenomegaly, jaundice and pancytopenia. Standard triple therapy was substituted with ethambutol, streptomycin and oral prednisolone and the patient made a dramatic recovery. The clinical symptoms of miliary tuberculosis are frequently non-specific and the onset of the illness is often insidious. The liver is involved in almost all patients with miliary tuberculosis, but massive hepatosplenomegaly and jaundice are rare. Standard triple-therapy should be discontinued when there is significant liver dysfunction, and corticosteroids should be considered for patients with miliary tuberculosis who fail to respond to conventional therapy.

Adrenal Cortex Hormones↗

A chamber and artificial dura method for long-term optical imaging in the monkey.

Optical imaging over extended periods of time in non-human primates presents serious challenges because the dura mater must be removed to expose the cortical surface. We present a novel nylon imaging chamber with a transparent artificial dura implant, which allows repeated, long-term optical recordings from the cortex. The cylinder of the chamber is inserted into a cranial trephination and held in place with a minimum of screws and acrylic cement. A round patch of artificial dura with a perpendicular wall protects the cortical surface and slows re-growth of dural tissue within the chamber. A cap, manufactured from the same material as the cylinder, is screwed into the chamber and seals it completely. Over a period of 1-4 months, the chamber required a minimum of maintenance and stayed infection-free without local antibiotic application. We repeatedly performed optical imaging in the same animal with the advantages of shortened preparation time. To permit precise alignment and comparison of maps obtained from different imaging sessions, we developed a program that calculated a 2-dimensional spatial transformation between maps of different magnifications, translations, and distortions. We suggest that these methods provide a practical solution to long-term optical imaging in the anesthetized or alert monkey. The exclusive use of non-metallic materials offers the benefit of a lighter and more compact implant, and the possibility to perform MRI scans after chamber implantation.

Anesthesia↗

Sinonasal angiosarcoma with marrow involvement at presentation mimicking malignant lymphoma: cytogenetic analysis using multiple techniques.

Angiosarcoma of the head and neck most commonly involves the skin of the scalp or face; primary involvement of the sinonasal region is exceedingly rate. We report a patient with sinonasal angiosarcoma who showed marrow involvement at presentation. Marrow aspiration smears showed many large, often segregated blast-like cells, mimicking malignant lymphoma. However, trephine biopsy revealed formation of anastomosing vascular spaces by the tumor cells and immunoreactivity for CD31, supporting a diagnosis of angiosarcoma. DNA ploidy analysis showed an apparent diploidy. Nevertheless, conventional cytogenetics demonstrated very complex chromosomal abnormalities with the presence of multiple hypodiploid clones, together with several near-triploid to near-tetraploid clones showing structural abnormalities involving chromosomes 1, 3, 4, 9, 14, 16, 17, 18, and 22. The identification of these karyotypic changes has been facilitated by the application of comparative genomic hybridization and spectral karyotyping.

Adult↗

Complications of frontal sinusitis in adolescents: case presentations and treatment options.

Frontal sinusitis in adolescents can be a serious condition because of the severity of potential complications and rapid progression of disease. These complications may arise as a result of extension of the infection intracranially, to the frontal bone, and to the orbit. Infection may spread hematogenously or by direct extension. A series of seven adolescent patients with complications of frontal sinusitis is presented. Surgical options are necessitated by the location and extent of infection and include trephination, frontal sinus obliteration, and craniotomy. Recent advances in endoscopic sinus surgery have provided surgeons another access to the frontal recess. However, a combined otolaryngological/neurosurgical approach is essential for patients with intracranial complications.

Abscess↗

The diagnosis and treatment of hairy-cell leukaemia.

The diagnosis of HCL is usually straightforward and is based on the identification of typical HCs in the blood and bone marrow. The suspected diagnosis is confirmed by a combination of TRAP cytochemistry, a distinctive immunophenotype and characteristic BM trephine appearances. Nucleoside treatment is highly effective in inducing prolonged remissions; relapsing patients can usually be successfully retreated with nucleoside. Monoclonal antibody therapy is a promising novel approach to the treatment of resistant disease.

Bone Marrow Examination↗

Defects of the rat premaxilla as a model of alveolar clefts for testing bone-inductive agents.

Critical-sized defects were made in the premaxillary bone of Wistar male rats using a surgical trephine and a low-speed dental engine as a model of the maxillary alveolar cleft for testing bone-inductive agents. The defects were treated with either 7 mg of demineralized bone matrix (DBM) or were left nongrafted. The nongrafted group healed mainly with fibrous connective tissue, with a small amount of bone formation at the periphery. There was no significant change in alkaline phosphatase activity and 45Ca incorporation. The DBM-grafted group produced new bone with osseous bridging in the defect by day 35. Alkaline phosphatase activity increased significantly from day 10, reaching a maximum on day 14, and 45Ca incorporation increased on day 14. These results indicate that this nonhealing bony wound of the premaxilla in rats may be useful as a model for studying the effect of bone-inductive agents on the healing of alveolar clefts.

Alkaline Phosphatase↗

Histologic and microradiologic comparison of block and particulate cancellous bone and marrow grafts in reconstructed mandibles being considered for dental implant placement.

PURPOSE: Patterns of healing were investigated in mandibles reconstructed with three different techniques to assess their readiness for implant placement. PATIENTS AND METHODS: The subjects were 10 patients who had undergone mandibular reconstruction with either nonvascularized iliac block bone grafts (group 1; 3 patients), particulate cancellous bone and marrow (PCBM) grafts (group 2; 3 patients) for mandibular discontinuity, or PCBM grafts for mandibular marginal defects (group 3; 4 patients). Six (groups 2 and 3) or 12 months (group 1) after mandibular reconstruction, bone biopsy specimens were obtained for histologic examination with a trephine bur. As controls, bone specimens were obtained from ungrafted mandibles of patients undergoing dental implant placement. Undecalcified specimens were embedded in polyester resin and examined by routine light microscopy and microradiography. RESULTS: The morphology of the specimens from group 1 was similar to that of group 2, but not to that of the control subjects. However, the morphology of specimens from group 3 was generally similar to that of control subjects. CONCLUSION: These results suggest that mandibular reconstruction with PCBM grafts allows the placement of dental implants sooner than reconstruction with block bone grafts.

Adult↗

Inhibition of neuronal nitric oxide synthase-mediated activation of poly(ADP-ribose) polymerase in traumatic brain injury: neuroprotection by 3-aminobenzamide.

Focal traumatic injury to the cerebral cortex is associated with early activation of the neuronal isoform of nitric oxide synthase (nNOS), where high concentrations of nitric oxide-derived free radicals elicit extensive DNA damage. Subsequent activation of the nuclear repair enzyme poly(ADP-ribose) polymerase (PARP) causes a severe energy deficit leading to the ultimate demise of affected neurons. Little is known about the temporal relationship of nNOS and PARP activation and the neuroprotective efficacy of their selective blockade in traumatic brain injury. To determine the relationship of nNOS and PARP activation, brain injury was induced by cryogenic lesion to the somatosensory cortex applying a pre-cooled cylinder after trephination for 6 s to the intact dura mater. Pre-treatment with 3-bromo-7-nitroindazole (BrNI; 25 mg/kg, i.p.), and pre- or combined pre- and post-treatment with 3-aminobenzamide (AB; 10 mg/kg (i.c.v.) or 10 mg/kg/h (i.p.)) were used to inhibit nNOS and PARP, respectively. Cold lesion-induced changes in the somatosensory cortex and neuroprotection by BrNI and AB were determined using immunocytochemistry and immunodot-blot for detection of poly(ADP-ribose; PAR), the end-product of PARP activation, and the triphenyltetrazolium-chloride assay to assess lesion volume. PAR immunoreactivity reached its peak 30 min post-lesion and was followed by gradual reduction of PAR immunolabeling. BrNI pre-treatment significantly decreased the lesion-induced PAR concentration in damaged cerebral cortex. Pre-treatment by i.c.v. infusion of AB markedly diminished cortical PAR immunoreactivity and significantly reduced the lesion volume 24 h post-injury. In contrast, i.p. AB treatment remained largely ineffective. In conclusion, our data indicate early activation of PARP after cold lesion that is, at least in part, related to nNOS induction and supports the relevance of nNOS and/or PARP inhibition to therapeutic approaches of traumatic brain injury.

Animals↗

Gelatinous bone marrow transformation in a case of idiopathic myelofibrosis: a morphological paradox.

A 74-year-old woman with severe, but asymptomatic weight loss was found to have splenomegaly, thrombocytosis, and neutrocytosis. A trephine biopsy showed a hypercellular bone marrow with a proliferation of abnormal megakaryocytes, mild reticulin fibrosis, and osteosclerosis, i.e., features of an early stage of idiopathic myelofibrosis. In contrast to this predominant pattern, the marrow also contained a distinct hypocellular focus of gelatinous transformation (GMT) in which hematopoietic and fat cells were replaced by gelatinous substances that were characterized as hyaluronic acid mucopolysaccharides histochemically. GMT is a rare disorder of unknown pathogenesis, and is an unspecific indicator of severe illness which most often occurs in patients with a background of weight loss. This is the first reported case of gelatinous changes in an otherwise fibrotic bone marrow, a constellation which a priori seemed to be incompatible.

Adipose Tissue↗

Megakaryocytopoiesis in bone marrow biopsies of patients with acquired immunodeficiency syndrome (AIDS). An immunohistochemical and morphometric evaluation with special emphasis on myelodysplastic features and precursor cells.

In 25 patients (22 males, 3 females--median age 39 years) with AIDS (CDC stages IV A-D) and no preceding myelotoxic therapy, morphometry and immunohistochemistry (CD 61-Y 2/51) was performed on trephine biopsies of the bone marrow to evaluate the megakaryocytic lineage. In comparison with megakaryocytes in the myelodysplastic syndromes (MDS) significant differences were evident. In AIDS this cell population revealed a size distribution within the normal range (control group) and no predominance of micromegakaryocytes characteristic for MDS. Furthermore, by determination of the form factors more irregular shapes of cell and nuclear perimeters could be shown. Finally, a not-evaluated number of precursors (promegakaryoblasts) was calculable. Particularly in those patients (n = 15) with AIDS-related severe thrombocytopenia the missing increase in the relative amount of promegakaryoblasts was conspicuous. This result was strikingly different from findings in idiopathic (autoimmune) thrombocytopenia and suggested an impairment of progenitor cell proliferation and differentiation in the acquired immunodeficiency syndrome. In conclusion, morphometry in combination with immunohistochemistry failed to establish characteristic myelodysplastic aspects of the megakaryocytic lineage in AIDS. For this reason, bone marrow lesions in this disorder should be properly termed HIV-myelopathy and not myelodysplasia.

Acquired Immunodeficiency Syndrome↗

Proliferating cell nuclear antigen (PCNA) expression of megakaryocytopoiesis in normal human bone marrow and reactive lesions with special emphasis on HIV-myelopathy.

A morphometric analysis was performed on bone marrow trephine biopsies using sequential double-immunostaining, to evaluate endoreduplicative activity of megakaryocytopoiesis. A total of 104 marrow specimens were studied with employment of monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen-PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa). In addition to the control group patients included non-specific inflammatory changes, HIV-myelopathy with normal or decreased platelet counts, idiopathic thrombocytopenic purpura (ITP), and finally reactive thrombocytosis (TH). To exclude an undue overexpression of PCNA, in a comparative pilot study we also applied MIB1 (Ki-67 antigen) on normal bone marrow specimens. In accordance with the various modalities of cell-cycle marker expression, no significantly different findings were disclosed. PCNA-labelling index was relatively low, ranging from 0.8 to 1.7% of the total megakaryocytopoiesis (promegakaryoblasts to mature platelet-shedding megakaryocytes). A significant relationship between megakaryocyte size and PCNA-expression was determinable. This implies that some of the cases with a prevalence of small megakaryocytes, like ITP, have the tendency to show a higher proportion of positively-stained cells. Moreover, this feature confirms a hypothesis postulating a decrease in the time for DNA-synthesis (S-phase) and a relative prolongation of the G1/G2-phases of the cell-cycle at higher ploidy levels (large-sized megakaryocytes). On the other hand, it may be speculated that some of the hyperpolyploid giant megakaryocytes may have reached their endstage of endoreduplication and enter into G0-phase. In comparison with the control group and the other entities under study, a significant reduction of PCNA-reactivity was recognizable in HIV-myelopathy accompanied by thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Macrophages (phagocytic-histiocytic reticular cells) in reactive-inflammatory lesions of the bone marrow and in myelodysplastic syndromes (MDS). An immunohistochemical and morphometric study by use of a new monoclonal antibody (PG-M1).

An immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow in 52 patients (28 males/24 females; age 68 years) with various subtypes of myelodysplastic syndromes (MDS) to determine the number of macrophages (phagocytic-histiocytic reticular cells). Quantifications included the haemosiderin-storing subpopulation (Prussian-blue reaction) of this lineage as well as the iron-free compartment. The latter was identified by a new monoclonal antibody (PG-M1) which is specifically directed against histiocytic reticular cells. Bone marrow specimens of individuals without haematological disorders and those showing reactive lesions served as controls. In comparison with the normal bone marrow and inflammatory changes (i.e. rheumatoid arthritis) 23 of the 52 patients with MDS revealed a significant increase in macrophages. This increase encompassed not only the iron-laden subpopulation but also the total number of phagocytic reticular cells. Accumulation of macrophages in MDS was speculated to be due to a premature and enforced degradation of dysplastic cell elements leading to phagocytosis of haemosiderin and debris material. Moreover, cells of the monocyte-macrophage system could be involved in the complex pathomechanism of fibrillogenesis, since in a considerable percentage of patients with MDS, an increase in reticulin (argyrophilic) fibres was noticeable. Our finding of an expansion of the macrophage compartment in about half of the patients with MDS is in keeping with results of cell culture studies on colony formation of granulocyte-macrophage precursors (CFU-GM).

Adult↗

Lung biopsy: methods, value, complications, timing, and indications.

Six methods of lung biopsy are discussed on the basis of literature reports: 1. Aspiration biopsy by fine needle, 2. split needle biopsy (Vim-Silverman), 3. cutting needle biopsy (Travenol), 4. trephine biopsy by rotating needle, 5. transbronchial biopsy, 6. open biopsy. Because of the high risk, biopsies with thick needles (methods 2--4) should be abandoned. Transbronchial biopsy is renounced because reliable results are only achieved in sarcoidosis which can be clearly diagnosed in high percentage of cases by other less dangerous procedures. In solitary tumors which could not be diagnosed by any other means aspiration biopsy is indicated because of its low risk and its diagnostic accuracy of more than 80%. In disseminated pulmonary disorders which cannot be diagnosed by any other means open lung biopsy is the most reliable method. The lung specimens can be taken under eye control. They should contain tissue from the transitional zone between diseased and unchanged areas, however. The specimens are usually big enough for additional electron and fluorescence microscopic examinations as well as dust analyses. The pathologist must be aware of all clinical data including X-ray pictures, laboratory findings, case history, and history of occupational and nonoccupational dust exposure. If these conditions are fulfilled and adequate methods are applied, lung biopsy provides diagnosis and prognosis, makes causal therapy possible, and amplifies the medical knowledge of pulmonary diseases.

Biopsy↗

Smokers' dysmyelopoiesis--bone marrow alterations associated with cigarette smoking.

Cigarette smoking is frequently associated with leukocytosis (with normal differential count) and polyglobulia in the peripheral blood. Corresponding studies on bone marrow alterations in smokers have not been done until now. We therefore investigated bone marrow trephine biopsies of 32 smoking persons. Biopsies had been mainly performed because of mild peripheral leukocytosis. In all cases we found a moderate increase in granulopoietic cells with a significant shift to the right and a distinct stimulation of phagocytic activity in macrophages. According to cytochemical findings, neutrophils are the major target of this phagocytic activity. We interpret these results as a smoking induced inhibition of locomotion in segmented neutrophils leading to an accumulation of mature polymorphs in the bone marrow with consecutive break-down and phagocytosis of senescent cells. We propose the designation "smokers' dysmyelopoiesis" for these changes.

Adult↗

A microradiographic investigation of cancellous bone healing after irradiation and hyperbaric oxygenation: a rabbit study.

PURPOSE: To analyze the effect of irradiation on cancellous bone healing at different times after irradiation and to study if hyperbaric oxygen therapy (HBO) would affect the bone healing capacity, when delivered directly after irradiation. METHODS AND MATERIALS: Rabbits were given a single dose of 15 Gy (60)Co radiation to one hind leg, the other hind leg serving as control. A standardized defect through the femoral metaphysis of the rabbits was created by a trephine drill biopsy at different times after irradiation. New bone formation in the defect was evaluated by a new biopsy through the previous defect after a healing time of 8 weeks. The mineral contents of the biopsies were analyzed by microradiography and microdensitometry. RESULTS: There was a large variation in the bone-forming capacity expressed as bone mineral content between the animals. No statistically significant differences could be detected regarding the effect of irradiation, HBO, or delayed surgery. Qualitative histology revealed more pronounced inflammation, fibrosis, and bone resorption in the irradiated bone. CONCLUSIONS: No definite conclusions can be drawn from the results of this study, however it might be hypothesized that cancellous bone recovers faster than cortical bone from radiation trauma.

Animals↗