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Peripheral and axial measurements of trabecular bone density in patients suspected of idiopathic vertebral osteoporosis.

In 18 patients with idiopathic crush fracture syndrome, iliac trabecular bone volume measured in 8 mm trephine biopsies correlated well with trabecular bone density as estimated in low thoracic or high lumbar vertebrae by computed tomography (CT). The CT of trabecular bone in the radius correlated poorly with the other two measurements, but it discriminated fairly well between patients and age-matched controls. These results suggest that abnormally low trabecular bone density values in the radius may be useful in predicting some patients at risk for crush fractures, but ranking patients in order of severity of axial bone loss after they have acquired a fracture requires measurements on the spine or iliac crest.

Aged↗

A reliable method for establishing viral infection in the rabbit by intranasal inoculation.

Bovine herpesvirus 1 (BHV-1) infection was established in the rabbit by a novel procedure which involved virus being injected through trephine openings on either side of the nose of anaesthetised animals. This method of intranasal inoculation produced more consistent reactions to BHV-1 inoculation, and both humoral and cell-mediated immune responses to the virus were of greater magnitude compared with those following per naris instillation of virus.

Animals↗

The prognostic significance of bone marrow metastases in small cell lung cancer patients.

One-hundred forty-six SCLC patients were classified as localised (56) or extensive (90) using chest X-ray, bronchoscopy, brain CT, bone scintigraphy, ultrasonography of the abdomen and bilateral bone marrow trephine biopsy. Bone marrow metastases were found in 28 cases. Patients with bone marrow metastases had significantly shorter time to progression (median 20 weeks) and significantly shorter survival time (median 31 weeks) than other patients with extensive disease (medians 30 and 46 weeks). Patients with bone marrow involvement had significantly more often metastases in three or more organs than others with extensive disease. The negative prognostic significance of bone marrow involvement was however independent of the negative prognostic significance of the number of organs with metastases.

Adult↗

A prospective comparison between magnetic resonance imaging, meta-iodobenzylguanidine scintigraphy and marrow histology/cytology in neuroblastoma.

A prospective comparison between magnetic resonance imaging (MRI), 123I meta-iodobenzylguanidine (mIBG) scintigraphy and posterior iliac crest marrow aspiration and trephine biopsy in 30 assessments (19 patients) showed concordance between the three techniques in 16 assessments (53.3%). In 10 (33.3%), MRI and mIBG revealed abnormalities not detected by marrow biopsy. MRI was the only technique to demonstrate marrow abnormality in four assessments (13.3%). In addition, MRI revealed more sites of abnormality in 16 parallel assessments. We conclude that MRI shows promise as a non-invasive means of detecting bone marrow infiltration by neuroblastoma, but that further evaluation of the specificity of MRI in this setting is indicated.

3-Iodobenzylguanidine↗

Role of osteopromotion in experimental bone grafting to the skull: a study in adult rats using a membrane technique.

This study explores the effect of an osteopromotive membrane technique in a mature animal model on the survival of membranous and endochondral bone inlays in mandibular defects and membranous bone onlays on the calvarial roof. Twenty-eight adult male rats received fibular or mandibular inlay bone grafts to trephine defects in the mandibular angle, as well as mandibular disc onlay grafts to the parietal and frontal bone regions. The results were assessed by gross inspection and light microscopy after 12 weeks. Membrane use markedly promoted bone deposition in the defects. The membranous bone inlays showed complete incorporation to the margins of the defect, whereas the endochondral grafts at all times were covered by a thin fibrous capsule and failed to incorporate. Onlay grafts generally resorbed substantially, but the grafts covered by a membrane seemed more active, developed an increased cancellous component, and showed less pronounced volumetric loss. The findings confirm the fact that a biological difference exists between membranous and endochondral bone. They also confirm the osteopromotive effect of the membrane technique, and suggest that the amount of bone needed for transplantation can be reduced using this method.

Animals↗

Osseous response to implanted natural bone mineral and synthetic hydroxylapatite ceramic in the repair of experimental skull bone defects.

The purpose of this study was to assess and compare the osseous responses to implanted particles of resorbable anorganic xenograft bone mineral and non-resorbable dense synthetic hydroxylapatite of two different granule sizes. Four trephine calvarial defects were produced in each of 13 adult rabbits. The experimental materials were subsequently implanted in three defects, leaving the fourth defect for control purposes. Six animals were killed 4 weeks after surgery and seven at 14 weeks. The tissue responses were assessed by contact radiography, light microscopy, and histometry. The biocompatibility of the implants was confirmed. All defects healed uneventfully, although the resorbable hydroxylapatite seemed to promote initial bone regeneration. The importance to orthognathic surgery of early and effective healing of bone gaps, as well as of the advantage of implant resorbability to bone remodeling, are discussed.

Absorption↗

A technique for the in vitro incubation of deer antler tissue.

1. A procedure for the in vitro incubation of velvet deer antler tissue was developed. Biopsy samples were collected in June with a trephine from 2 adult white-tailed deer and incubated in modified BGJb medium up to 48 hr. Calcium (Ca) and hydroxyproline (OH-proline) concentrations in the tissue were determined. 2. A significant increase (P less than 0.05) in Ca was exhibited at 4 and 8 hr of incubation, and, after replenishment of media, at 48 hr. 3. Hydroxyproline concentrations continued to rise throughout the duration of the incubation period and were significantly higher than controls (P less than 0.05) at 16, 24, and 48 hr. 4. Results suggest antler tissue can be incubated in vitro with the protocol described, although length of incubation may vary with parameter measured.

Animals↗

Effect on biochemical markers of brain injury of therapy with deferoxamine or superoxide dismutase following cardiac arrest.

Iron-mediated lipid peroxidation by oxygen radical mechanisms is thought to be a contributing factor to neurological injury during reperfusion following resuscitation from cardiac arrest. This study was designed to examine and compare the effects of an iron chelator (deferoxamine) and superoxide dismutase (SOD) on brain lipid peroxidation and tissue ions after eight hours of reperfusion following a 15-minute cardiac arrest. This sampling time was chosen because other work with this model has shown severe ionic and ultrastructural derangement at this point. Twenty-three dogs were anesthetized with ketamine and halothane and divided into four groups. Six dogs were nonischemic controls (group I). In the remaining dogs, a 15-minute cardiac arrest was induced with KCl. Resuscitation was begun with internal cardiac massage and artificial ventilation. After five minutes of artificial perfusion, internal defibrillation was performed to restart the heart. All dogs were resuscitated and supported by a standard intensive care (SIC) protocol for eight hours. Six resuscitated dogs served as SIC controls (group II). Six were treated with deferoxamine, 200 mg/kg loading dose and 100 mg/kg/h maintenance drip (group III), and five were treated with SOD, 1,000,000 units bolus and 500,000 units/h drip (group IV). All drugs were administered intravenously immediately postresuscitation. At eight hours postresuscitation, a 3-g portion of parietal cerebral cortex was obtained through a trephine hole. The sample was assayed for tissue malondialdehyde (MDA) by the thiobarbituric acid test, the double bond content of the tissue lipids (lipid unsaturation index, LUSI), and total tissue content of K and Na.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A brief history of epilepsy and its therapy in the Western Hemisphere.

The history of epilepsy and its treatment in the western world dates back at least 4 millennia to the ancient civilization of the middle east. Past and present treatments have been empirical, usually reflecting the prevailing views of epilepsy, be they medical, theological or superstitious. Ancient physicians relied on clinical observation to distinguish between epileptic syndromes and infer their cause. Early pathophysiological theories of epilepsy correctly identified the brain as the site of the problem, but emphasized incorrect causes such as an excess of phlegm in the brain. Treatments consisted of prescribed diets or living conditions, occasional surgery such as bloodletting or skull trephination and medicinal herbs. These treatments, often ineffective, had the intellectual advantage of being based on pathophysiological principles, unlike current, more empirical, therapies. The unfortunate but widely held view of epilepsy as being due to occult or evil influences gained adherents even in the medical world during ancient times, and the later acceptance of Christianity allowed theological interpretations of seizures as well. Magical or religious treatments were more frequently prescribed as a result, practices which persist to this day. In the Renaissance an attempt was made to view epilepsy as a manifestation of physical illness rather than a moral or occult affliction, but it was during the Enlightenment that epilepsy was viewed along more modern lines, helped by advances in anatomy and pathology and the development of chemistry, pharmacy and physiology. The idea that focal irritation may cause seizures came about from clinical and experimental work, and was supported by the successful control of seizures by the (sedative) bromides and barbiturates in the late 19th century. The introduction of phenytoin showed that non-sedative drugs could be effective in controlling seizures as well, and the development of in vivo seizure models widened the scope of pharmaceutical agents tested for their efficacy against epilepsy. Increasing knowledge of the cellular mechanisms of epilepsy will, hopefully, allow the development and introduction of drugs with increasing specificity against seizure activity and the development of epilepsy.

Epilepsy↗

Hyaluronate and its receptors in bone marrow.

Cell-cell and cell-matrix interactions, which are mediated by cell adhesion molecules, play a fundamental role during many cellular processes including growth, differentiation, cell migration and cancer metastasis. One molecule playing a major role in these processes is the CD44 surface receptor, which is expressed in a wide range of cells including many cells of the hemopoietic system, where it mediates the interaction with its major ligand, hyaluronate. However, little is known about CD44 and hyaluronate in bone marrow and this was investigated immunohistochemically in trephine biopsies and in cultivated human bone marrow stromal cells. In biopsy specimens, patches of hyaluronate deposition were detected in the extracellular matrix (ECM). However, most of the areas of the ECM were devoid of hyaluronate. Single mast cells and lymphocytes scattered throughout the marrow were CD44 immunopositive. Marrow-derived stromal cells (MDSC) expanded in cell culture were immunopositive for CD44, hyaluronate synthase, and hyaluronate. Hence, a marked difference between CD44 immunolocalisation and hyaluronate deposition can be observed between in situ and under cell culture conditions. Since in normal marrow in situ the number of CD44 immunopositive cells was low, interactions of CD44 and hyaluronate would appear to not to play a major role in cell adhesion in the normal bone marrow.

Bone Marrow↗

Impact of phototherapeutic keratectomy on the outcome of subsequent penetrating keratoplasty in patients with stromal corneal dystrophies.

PURPOSE: To examine the impact of previous phototherapeutic keratectomy (PTK) on the outcome of subsequent penetrating keratoplasty (PK) in patients with stromal corneal dystrophies. DESIGN: Retrospective, cross-sectional, clinical single-center study. METHODS PATIENT POPULATION: Fifteen patients (21 eyes) age 39.9 +/- 11.4 years. INCLUSION CRITERIA: Primary homologous PK performed in phakic patients with granular or macular dystrophy; no use of combined surgical procedures; defined graft size and technique. The study group comprised eight eyes of five patients, PK performed 3.7 +/- 2.3 years after PTK. The control group (no previous PTK) comprised 13 eyes of 10 patients. In both groups, 38% had granular and 62% had macular dystrophy. Intervention Procedures: Phototherapeutic keratectomy was performed using a 193 nm excimer laser. All PKs were also performed using this laser, with trephination using a metal mask. Subjective refractometry (trial lenses), standard keratometry (Zeiss ophthalmometer), and corneal topography (Tomey TMS-1) were performed preoperatively, 6 months after PK, and after first and second suture removal (1.1 +/- 0.2 years; 1.6 +/- 0.2 years). MAIN OUTCOME MEASURES: Keratometric, topographic net astigmatism, and refractive cylinder; keratometric and topographic central power; best-corrected visual acuity (BCVA); surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity (PVA). RESULTS: Refractive power and astigmatism, BCVA, and PVA values did not differ significantly between the two groups at any time-point; SRI tended to be better in the study group after first suture removal (P =.05). CONCLUSION: Preceding PTK does not appear to impair the outcome of subsequent penetrating keratoplasty in stromal corneal dystrophy patients.

Adult↗

A device to facilitate limbal stem cell procurement from eye bank donor tissue for keratolimbal allograft procedures.

PURPOSE: To develop a device that facilitates the procurement of corneal limbal stem cell grafts for keratolimbal allograft procedures used in the treatment of ocular surface disease associated with stem cell deficiency. DESIGN: Description of device design and technique for use. METHODS: The device is composed of a pedestal with a convex surface mounted to a flat platform. A corneoscleral button placed endothelial side down and centrally upon the convexity is secured by suction conveyed through a hollowed core in the pedestal that connects to fenestrated openings on the convex surface. A donut-shaped stainless steel ring placed on tension by springs braces the peripheral tissue. A circular corneal incision is created of a desired thickness by a suction trephine, and a crescent blade is utilized to peripherally dissect a donut-shaped keratolimbal allograft. RESULTS: This device facilitated the harvesting of the keratolimbal allograft tissue from four eye bank donor practice corneoscleral buttons and was then used to successfully procure grafts from six corneoscleral buttons used in three keratolimbal allograft procedures in three patients, one each with aniridia, alkali burn, and drug-induced limbal stem cell deficiency. CONCLUSIONS: The described device effectively facilitates procurement of corneoscleral buttons for keratolimbal allograft procedures. It appears to offer advantages over freehanded techniques and previously described devices used for the same purpose.

Cell Separation↗

Changes in corneal power and refraction due to sequential suture removal following nonmechanical penetrating keratoplasty in eyes with keratoconus.

PURPOSE: To assess the changes in corneal power and refraction due to sequential suture removal after penetrating keratoplasty (PK). DESIGN: Retrospective consecutive case series. METHODS: setting: Clinical practice. study population: We studied 67 phakic keratoconus eyes (central excimer laser trephination, primary keratoplasty, graft/recipient diameter 8.1/8.0 mm; double running suture) in this longitudinal study. main outcome measures: Zeiss keratometry (equivalent power (KEQ), astigmatism (KAST)), corneal topography (equivalent power (TEQ), astigmatism (TAST)) and subjective refractometry (spherical equivalent (SEQ), refractive cylinder (RAST)) were assessed with sutures in place (interval 1), with one suture out (interval 2), and with all sutures out (interval 3). observation procedure: Corneal power and refraction was decomposed into vector components and the changes were derived between time stages. RESULTS: The mean follow-up period was 3.9+/-1.7 years. At interval 1, the axes of KAST/TAST/RAST were almost randomly distributed. At interval 2, the with/against the rule component of KAST/TAST/RAST decreased slightly and the oblique component increased significantly, so that the axes tended to have a preferred oblique direction. At interval 3, the with/against the rule component of KAST/TAST/RAST increased slightly and the oblique component decreased significantly, so that the with/against the rule component exceeded the oblique component by approximately 23%/28%/25%. Median KEQ/TEQ/SEQ changed by 0.64/0.62/-1.11 diopters (interval 1 to interval 2) and by -0.85/-0.90/1.56 diopters (interval 2 to interval 3). CONCLUSIONS: As a result of removal of the first running suture, corneal astigmatism as well as the refractive cylinder tend to oblique axes. As a result of removal of the second running suture, the final corneal astigmatism and refractive cylinder tend to orientation axes with/against the rule.

Astigmatism↗

Harvesting of bone from the iliac crest--comparison of the anterior and posterior sites.

In 1998 we harvested a total of 127 bone grafts from the iliac crest of 65 male and 53 female patients aged 8-80 years. We measured the quantity of bone obtained, the operating time and the donor site morbidity of the anterior approach (n=81) compared with the posterior approach (n=46). The mean volume of bone harvested was 15 cm(3) (range: 9-25.5) of monocorticocancellous- or bicortico-cancellous bone chips or those from a trephine bur. The mean operating time for the anterior approach was 35 min (range: 22-48), for the posterior approach 40 min (range: 32-55). There were 15 complications, which were limited to those in whom the volume of bone exceeded 17 cm(3). The posterior approach caused less morbidity, notably in the form of significantly less pain and irregularity of gait. The patient has, however, to be repositioned during operation, which added to its total duration.

Adolescent↗

Elevated serum FGF23 concentrations in plasma cell dyscrasias.

Fibroblast growth factor 23 (FGF23) is now recognized as a key regulator of phosphate metabolism. Numerous reports have found elevated serum FGF23 concentrations in oncogenic osteomalacia associated with mesenchymal tumors. Hypophosphatemic osteomalacia more rarely occurs in non-mesenchymal tumors. We identified elevated serum FGF23 levels in one patient with chronic lymphatic leukemia (CLL) and hypophosphatemia, prompting us to examine FGF23 concentrations in other patients with B-cell neoplasms. FGF23 levels were elevated in several patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS), and were significantly associated with serum paraprotein and beta-2 microglobulin concentrations in these patients. Hypophosphatemia was not observed even in those patients with elevated FGF23, and a weak positive correlation was noted between serum FGF23 and phosphate concentrations. Malignant plasma cells in bone marrow trephines from patients with myeloma showed cytoplasmic expression of FGF23, similar to the cytoplasmic localization of FGF23 already described in mesenchymal tumors associated with oncogenic osteomalacia. Our findings contribute to an expanding literature regarding abnormal FGF/FGF receptor-signaling in myeloma. The absence of hypophosphatemia in these cases suggests either that FGF23 produced by clonal B-cells lacks systemic bioactivity or that other factors contribute to maintain serum phosphate. We suggest that the relationship between FGF23 and skeletal disease associated with plasma cell dyscrasias deserves further study.

Aged↗

Aggressive systemic mastocytosis complicated by protein-losing enteropathy.

A 46-year-old woman was admitted to the hospital with complaints of chronic diarrhoea, vomiting and severe muscle weakness. Clinical examination showed a lethargic, malnourished, dehydrated patient with ascites and bilateral leg oedema. Laboratory evaluation revealed mild normochromic normocytic anaemia and severe hypoproteinaemia with hypoalbuminaemia. Upper gastrointestinal endoscopy showed a thickened, friable duodenal mucosa with multiple erosions. Colonoscopy revealed nodular, pseudopolypoid lesions with patchy erosions in the left hemicolon. Haematoxylin-eosin stained sections from biopsies of endoscopically abnormal bowel segments showed multi-focal aggregates of large, histiocyte-like cells with abundant pale cytoplasm in the lamina propria. These cells were negative on PAS, Ziehl-Neelsen, Giemsa and toluidine blue stains. Their immunophenotype was CD68 (+), c-kit/CD117 (+) and mast cell tryptase (+), which is consistent with mast cells. A trephine biopsy showed diffuse replacement of the bone marrow by atypical, monomorphic, frequently spindle-shaped mast cells. No associated haematopoietic malignancy was detected. The final diagnosis was aggressive systemic mastocytosis with involvement of the gastrointestinal tract complicated by protein-losing enteropathy. This association has not been reported previously. The patient has been treated with prednisolone and interferon-alpha and has since recovered.

Anti-Inflammatory Agents↗

Temporal expression of proteoglycans in the rat limb during bone healing.

Proteoglycans found in the bone extracellular matrix and on the cell surface can complex with HBGFs such as the FGFs, TGFs and BMPs which are known to play key roles in regulating fracture healing. Here we have studied the expression of key PGs during the bone repair process in order to determine the relationship between PG expression and healing status. We created non-critical sized trephine defects just proximal to the distal end of the tibial crest of adult male Wistar rats and examined the healing process histologically as well as by monitoring the temporal expression of mRNA transcripts for ALP, OP and OC, together with HSPG, CSPG and FGF-FGF receptor expression. Following surgery, animals were allowed to recover, and then euthanized after 7, 14, 21 and 28 days post-surgery, at which time tissue was harvested for histological examination and total RNA extracted and the mRNA transcripts examined by quantitative real-time PCR. HS and CSPG expression was generally observed to increase in the days immediately following injury, reaching peak expression two weeks post-surgery. This was followed by a gradual return to basal levels by day 28. The expression patterns of PGs were broadly similar with those of ALP, OP and FGFRs. The increase of mRNA expression for many key PGs detected during bone healing coincided with the elevation of bone markers and FGFRs, and provides further evidence that PGs involved in bone repair act in part through susceptible growth factors, including the FGF/FGFR system. The data presented here indicates that increased proteoglycan expression is involved in the early stages of bone healing at a time when previous studies have shown that the levels of HBGFs are maximal. Hence there exists a rationale for an exploration of the use of exogenous PGs as an adjunct therapy to potentiate the powerful effects of these factors and to augment the natural healing response.

Animals↗

Definition and diagnosis of sporadic and familial chronic lymphocytic leukemia.

This article describes the main defining criteria for chronic lymphocytic leukemia (CLL) and its differential diagnosis from closely related B-cell disorders. In addition to the morphology of circulating lymphocytes, the key diagnostic aid is the "CLL score" based on the typical immunophenotype of CLL as ascertained with five reagents: CD5, CD23, CD79b (or CD22), FMC7, and intensity of SmIg staining. The concepts of polyclonal and monoclonal B-cell lymphocytosis are defined with focus on the latter and its incidence in elderly individuals and its significant increase in healthy relatives from CLL families. The value of flow cytometry in the analysis of minimal residual disease after therapy also is discussed with a comparison with findings in bone marrow trephine biopsies. No candidate gene has been linked to the high incidence of CLL (10%) seen in families of patients with this disease.

Humans↗