Biomedical subjects

S Goodman

Publications and source records attributed to S Goodman.

At least 55 records · Page 3Linked to original sources

PubMed2001

Is total body irradiation a necessary component of preparative therapy for autologous transplantation in non-Hodgkin's lymphoma.

Between September 1986 and June 1998, 157 patients with low grade, intermediate grade, or high grade lymphoma underwent autologous transplantation at a single institution. Two preparative regimens were used: cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (N=110) and cyclophosphamide, BCNU, etoposide (CBV) (N=47). The two groups were not significantly different with respect to source of stem cells, gender, stage at presentation, incidence of prior bone marrow involvement, sensitivity to salvage therapy, or histologic grade of lymphoma. The CBV group was significantly older, 49% of patients over age 50, as compared to 26% of patients over age 50 for the CY-VP-TBI group. Response rates and the incidence of fatal toxicity were similar for the two groups. Five year actuarial survival was 31% +/- 9% for CBV and 38% +/- 5% for CY-VP-TBI, p =.85. In a multivariate analysis, in which preparative regimen, age, histologic grade of lymphoma, and sensitivity to salvage therapy were the independent variables, TBI was not significantly associated with survival, and the direction of the trend was for TBI to be less effective than CBV. TBI does not appear to be an essential component of preparative therapy for autologous transplantation in patients with lymphoma.

Adolescent↗

PubMed2001

Intensified preparative regimens and allogeneic transplantation in refractory or relapsed intermediate and high grade non-Hodgkin's lymphoma.

Between September 1986 and June 1998, 32 patients with relapsed or refractory intermediate or high grade lymphoma received intensified preparative therapy and underwent allogeneic transplantation at a single institution. Patients were considered for allogeneic transplantation if they failed to respond to initial therapy, failed to respond to salvage therapy, relapsed after autologous transplantation, had bone marrow involvement, or failed attempts to harvest autologous stem cells. Patients had a median age of 39 years and had generally received at least two chemotherapy regimens. Five year actuarial survival (S) was 16% +/- 6%; median survival was 4 months. Survival was significantly worse in patients who had received high intensity brief duration chemotherapy prior to transplantation and was also significantly worse in patients who did not receive total body irradiation (TBI). This likely reflects the fact that the patients with the most resistant disease had required local radiotherapy and could not receive TBI. While treatment related mortality played a major role in limiting the effectiveness of allogeneic transplantation, in this heavily pre-treated population of patients with resistant disease, only 39% of patients achieved a complete response following allogeneic transplantation, and in only 40% of that group was long term disease free survival achieved.

Actuarial Analysis↗

PubMed2001

Limited efficacy of intensified preparative regimens and autologous transplantation as salvage therapy in high grade non-Hodgkin's lymphoma.

Between 9/86 and 6/98, 22 patients with relapsed or refractory high grade lymphoma received intensified preparative therapy and underwent autologous transplantation at a single institution. Two intensified preparative regimens were used--cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (N=17) and cyclophosphamide, BCNU, etoposide (CBV) (N=5). For all patients undergoing autologous transplantation, 5 year actuarial survival (S) and 5 year event free survival (EFS) were only 18% +/- 8%. Treatment related mortality was 14% overall but only 8% in patients receiving G-CSF or GM-CSF. Survival was significantly inferior to the survival observed in a concurrent series of patients with intermediate grade lymphoma, 34% +/- 6%, p < .05. Using high dose therapy in conjunction with autologous transplantation at the time of relapse may not be as valuable a strategy in high-grade lymphoma as in intermediate grade lymphoma although most studies combine the two disorders. Alternative strategies for the use of transplantation in high grade lymphoma, such as the use of transplantation as consolidation therapy, need to be investigated.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

In vivo therapy of malignant melanoma by means of antagonists of alphav integrins.

Integrin alphavbeta3 (vitronectin receptor) has been implicated in human malignant melanoma progression and angiogenesis as a receptor that provides survival signals. However, little is known about the therapeutic potential of antagonists of alphavbeta3. In this report, we characterize the activities of 2 antagonists of alphavbeta3 integrins: a human specific monoclonal antibody (MAb), 17E6, and a cyclic RGD peptide that blocked cell adhesion and induced detachment of previously substrate-attached cells in vitro. In vivo, alphavbeta3 antagonists behaved as anti-tumor drugs in a dose- and time-dependent manner. Moreover, different therapeutic treatments proved to be effective even in the therapy of established macroscopic tumor masses, thus supporting the use of these antagonists in clinical therapy. Using a panel of 6 human melanomas and 5 carcinomas, MAb 17E6 efficiently blocked the in vivo tumor growth of melanomas expressing alphavbeta3 as xenografts but did not affect the alphavbeta3-negative (although alphav integrin-positive) tumors. This demonstrated that alphavbeta3 is a pivotal integrin for the growth of human melanomas. Furthermore, since MAb 17E6 does not recognize murine alphavbeta3, the effect is due only to the direct anti-tumor activity and not to the well-known anti-angiogenic activity of alphav-integrin antagonists. Taken together, our results confirm the essential role of alphavbeta3 integrin in the growth of human malignant melanoma in vivo and provide strong evidence of the therapeutic potential of alphav-integrin antagonists for the treatment of such tumors.

Animals↗

PubMed2000

Pulse oximetry is a poor predictor of hypoxemia in stable children with sickle cell disease.

OBJECTIVE: To evaluate the accuracy of the pulse oximeter to detect hypoxemia in patients with sickle cell disease in an ambulatory care setting. STUDY DESIGN: Simultaneous measurements of PaO(2), arterial oxygen saturation by co-oximetry (criterion standard), and pulse oximetry were performed in 21 children with sickle cell disease during 22 outpatient visits. The bias and precision of the pulse oximeter compared with measured arterial oxygen saturation by co-oximetry were determined. The sensitivity, specificity, and positive and negative predictive values of the pulse oximeter to detect hypoxemia (PaO(2) <70 mm Hg) were also calculated. RESULTS: The mean difference between pulse oximetry and measured oxygen saturation (bias) was 5.0% and the SD (precision) was 5.3. Twenty-one patients had a PaO(2) greater than 70 mm Hg; 7 of these (33%) were predicted to be hypoxic by pulse oximetry with values less than 93%, for a specificity to detect normoxia of 67%. CONCLUSION: Making treatment decisions based on pulse oximetry data alone in patients with sickle cell disease who are not acutely ill may be inappropriate.

Adolescent↗

PubMed2000

Effects of local infusion of TGFbeta on bone ingrowth in rabbit chambers.

The local delivery of exogenous growth factors may help achieve a stable, long-lasting prosthetic interface around primary and revision joint replacements. This study examines the effects of local infusion of transforming growth factor beta (TGFbeta) in an in vivo model of tissue differentiation within bone. The Drug Test Chamber was implanted in the proximal medial tibial metaphysis of 8 mature rabbits unilaterally. The chamber contained a 1 x 1 x 5 mm canal for tissue ingrowth. The chamber was connected to an osmotic diffusion pump via polyvinyl tubing. 3.5 microg of recombinant TGFbeta1 was infused for 1 day or 1 week with subsequent harvesting of the ingrown tissue after 3 weeks. Each TGFbeta treatment was followed by two, 3-week infusions of carrier alone and harvesting of the ingrown tissue. TGFbeta for 1 day increased, and TGFbeta for 1 week decreased the percentage of bone in the chamber, compared to the initial control harvest after carrier alone. These changes, however, did not reach statistical significance. The number of vitronectin receptor positive cells in total, adjacent to bone and away from bone was higher after treatment with TGFbeta for 1 day, compared to 1 week. In an "unperturbed" bone ingrowth system (i.e., if bone ingrowth is not initially suppressed by other stimuli), this dose of TGFbeta did not enhance bone ingrowth using the DTC model.

Animals↗

PubMed2000

Will the use of low-molecular-weight heparin (enoxaparin) in patients with acute coronary syndrome save costs in Canada?

BACKGROUND: One-year follow-up data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial show that use of low-molecular-weight heparin (enoxaparin) compared with unfractionated heparin in patients hospitalized with unstable angina or non-Q-wave myocardial infarction is associated with a 10% reduction in the cumulative 1-year risk of death, myocardial infarction, or recurrent angina. Given the higher acquisition cost of enoxaparin relative to unfractionated heparin, we assessed whether the reduced use of revascularization procedures and related care makes enoxaparin a cost-saving therapy in Canada. METHODS AND RESULTS: We analyzed cumulative 1-year resource use data on the 1259 ESSENCE patients enrolled in Canadian centers (40% of the total ESSENCE sample). Patient-specific data on use of drugs, diagnostic cardiac catheterization, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, and hospital days were available from the initial hospital stay and cumulative to 1 year. Hospital resources were costed with the use of data from a teaching hospital in southern Ontario that is a participant in the Ontario Case Costing Project. During the initial hospital stay, use of enoxaparin was associated with reduced use of diagnostic catheterization and revascularization procedures, with the largest effect being reduced use of percutaneous transluminal coronary angioplasty (15.0% vs 10.6%; P =.03). At 1 year, the reduced risk and costs of revascularization more than offset increased drug costs for enoxaparin, producing a cost-saving per patient of $1485 (95% confidence interval $-93 to $3167; P =.06). Sensitivity analysis with lower hospital per diem costs from a community hospital in Ontario still predicts cost savings of $1075 per patient over a period of 1 year. CONCLUSIONS: The acquisition and administration cost of enoxaparin is higher than for unfractionated heparin ($101 vs $39), but in patients with acute coronary syndrome, the reduced need for hospitalization and revascularization over a period of 1 year more than offsets this initial difference in cost. Evidence from this Canadian substudy of ESSENCE supports the view that enoxaparin is less costly and more effective than unfractionated heparin in this indication.

Adult↗

PubMed2000

Intensified preparative regimens and autologous transplantation in refractory or relapsed intermediate grade non-Hodgkin's lymphoma.

Between September 1986 and June 1998, 99 patients with relapsed or refractory IGL received intensified preparative therapy and underwent autologous transplantation at a single institution. Two intensified preparative regimens were used: cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (n = 66) and cyclophosphamide, BCNU, etoposide (CBV) (n = 33). As clinical features and results were not different for the two preparative regimens, results were combined. For all patients undergoing autologous transplantation, 5-year actuarial overall survival (OS) was 34% +/- 6%; 5-year event-free survival (EFS) was 26% +/- 5%. For patients who responded to primary therapy, salvage therapy, or both, OS was 42% +/- 7%; for non-responders to prior therapy, OS was 14% +/- 7%, P < 0.025. OS was better among patients responding to salvage therapy (50% +/- 9%), than among patients who had a complete response to initial therapy, but failed to respond or were untested/unevaluable with respect to salvage therapy (26% +/- 10%; P < 0.025). On multivariate analysis, response to salvage therapy was associated with survival following autologous transplantation (P < 0. 005). Treatment related mortality was 9% overall and only 6% after G-CSF and GM-CSF were introduced into routine clinical practice. High-intensity preparative therapy is highly effective, with acceptable treatment-related mortality, in patients with IGL who have responded to induction therapy, salvage therapy, or both. The best responses are observed in patients responding to salvage therapy. Randomized prospective studies will be needed to further define the role of intensified preparative regimens. Bone Marrow Transplantation (2000) 25, 257-262.

Adolescent↗

PubMed2000

Inter-regional differences and outcome in unstable angina; analysis of the international ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events.

AIMS: Worldwide there is a large variation in outcome (death, myocardial infarction and recurrent myocardial infarction) in patients with unstable angina or non-Q wave myocardial infarction. These variations may be explained by differences in characteristics of the presenting patients. Here we describe differences in patient presentation, treatment protocols and outcome and we investigate their relationship using data from the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) trial. METHODS: A total of 2981 patients from six countries which enrolled more than 100 patients were included in the present analysis: United States, Canada, Argentina, France, the Netherlands and United Kingdom. Logistic regression analysis was performed to determine the effect of baseline characteristics on regional outcome. RESULTS: At day 30, the lowest triple end-point rate, irrespective of study drug treatment, was noted in the Netherlands (18.9%) and the highest in Argentina (30.5%). A model including the variables age > or = 65 years, prior angina, diabetes, prior aspirin use, ECG changes at baseline and diagnosis of non-Q wave myocardial infarction and dummy variables for Argentina and France resulted in concordance of about 60%. CONCLUSIONS: Inter-regional differences in outcome in unstable angina and non-Q wave myocardial infarction patients can reasonably well be explained by differences in patient characteristics. However, other so far unidentified variables present in Argentina and France also contributed to differences in outcome and their effect warrants further investigation.

Angina, Unstable↗

PubMed2000

High oxygen concentration exacerbates cardiopulmonary bypass-induced lung injury.

OBJECTIVE: To investigate the effect of ventilation with 100% oxygen on lung injury associated with surgery involving cardiopulmonary bypass (CPB). DESIGN: A prospective randomized study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing coronary artery bypass graft surgery with CPB. INTERVENTIONS: Patients were randomized to receive 100% oxygen (Oxygen group) or 50% oxygen (Air group) throughout surgery. During CPB, patients' lungs in the Air group were flushed with air and in the Oxygen group with 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Lung injury was evaluated by arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio and cytokine levels (tumor necrosis factor-alpha and interleukin-8) in blood and bronchoalveolar lavage fluid measured before and after CPB. The lowest PaO2-FIO2 value was observed after 40 minutes following the completion of CPB in both groups. PaO2-FIO2 values 6 hours after CPB were not different from baseline in the Air group but remained lower (359+/-63 mmHg and 298+/-78 mmHg; p = 0.013) in the Oxygen group. Blood cytokine levels rose during surgery in both groups. Bronchoalveolar lavage levels of interleukin-8 did not change, whereas tumor necrosis factor-alpha increased only in the Oxygen group (p = 0.035). CONCLUSIONS: A significant decrease of oxygenation was observed in the early post-CPB period in both groups of patients, with delay in recovery in patients treated with 100% oxygen. A larger increase of the proinflammatory cytokines was found in patients treated with 100% oxygen. High oxygen concentrations during surgery with CPB should be used only when specifically required.

Bronchoalveolar Lavage Fluid↗

PubMed2000

The correlation between presenting ST-segment depression and the final size of acute myocardial infarcts in patients with acute coronary syndromes.

The use of reperfusion therapy in patients with ST elevation acute coronary syndromes had been established. However, reperfusion therapy is usually considered contra-indicated in those with ST depression, despite the knowledge that regional posterior infarction is typically indicated by ST depression maximal in leads V1 to V3 and nonregional subendocardial infarction is typically indicated by marked ST depression maximal in other leads. This study of patients with non-ST-elevation acute coronary syndromes investigates the quantitative relationship between presenting ST depression and final QRS changes in both of these subgroups. The final QRS score was significantly higher (2.44 points) than that of a control group with not ST depression, (1.55 points) in the group with maximal ST depression in V1 to V3 (P = 0.04). However, in the entire population, there was a highly significant correlation (P = .003) between the sum of the presenting ST depression and the final QRS score. Trials of reperfusion therapy will be required to determine if such evolution to electrocardiogram documented acute myocardial infarction can be prevented in patient with marked ST depression acute coronary syndromes.

Case-Control Studies↗

PubMed2000

A controlled study of vigabatrin and visual abnormalities.

AIMS: To assess the visual function in epileptic patients who have received vigabatrin; to compare this with the visual function in similar epileptic patients who have never received vigabatrin; to investigate whether the severity of visual field defect (VFD) is related to the dose of vigabatrin; to consider other factors that may correlate with the severity of VFD. METHODS: 21 consecutive patients who had taken vigabatrin at some time in their lives were enrolled from the epilepsy clinic of the Royal Shrewsbury Hospital and were compared with a group of 11 otherwise similar patients with epilepsy who had never received vigabatrin. One patient taking vigabatrin was excluded from the study because her visual field results were unreliable because of multi-infarct dementia. 15 patients were taking vigabatrin at the time of the study (VC), the other five had taken vigabatrin some time in the past (VP). Each patient underwent static perimetry using either the two point or the three point full field 120 screening program on the Humphrey visual field analyser, followed by an ophthalmic examination to rule out ocular causes for VFDs. The visual fields from each patient were then analysed using a method devised to convert the VFD into percentage defect in both eyes. In patients with known cerebral pathology that may affect the visual pathway, only the unaffected homonymous hemifield was used. RESULTS: Nine of 20 (45%) patients in the vigabatrin group (VC and VP) complained of blurring of vision compared with two of 11 (18%) controls. Four patients (20%) in the vigabatrin group described flickering lights compared with one control (9%). None had a posterior vitreous detachment. Three of 30 (7.5%) eyes in the VC group had distant visual acuity of 6/12 or worse compared with three of 22 (9%) controls and five of 30 (16.7%) had near visual acuity worse than N6 compared with one of 22 (4.5%) in the control group. A mean of 1.73 Ishihara plates were misread in VC patients compared with 0.2 in the VP group and 0.18 in the controls. 11 of 15 (73.3%) patients in the VC group had greater than 10% VFDs as opposed to one of 11 (9.1%) controls (chi(2) test, p=0. 002). In 12 of 15 (80%) VC patients the percentage VFD was greater in the nasal hemifields than the temporal hemifields compared with six of 11 (54.5%) controls. Significant correlation was found between the severity of VFD and the total dose of vigabatrin ingested for the 20 patients exposed to vigabatrin (VC and VP: Spearman correlation coefficient=0.525; p=0.002), for the 15 patients taking vigabatrin at the time of examination (VC: Spearman correlation coefficient=0.568; p=0.002). CONCLUSION: This pilot study suggested that epileptic patients taking vigabatrin are at much higher risk of developing VFDs compared with epileptic patients on other antiepileptic drugs. The total ingested dose of vigabatrin correlated significantly with the severity of VFDs especially in those patients who had not stopped taking vigabatrin. In our group we found that those who had taken a total dose of 1500 g or more of vigabatrin were at risk of developing significant visual field defects.

Adult↗

PubMed2000

Interferon-gamma downregulates ion transport in murine small intestine cultured in vitro.

Effects of IFN-gamma on mammalian small intestinal ion transport were studied in vitro using incubated sheets of murine small intestine in Ussing chambers. In oxygenated standard culture medium containing hydrocortisone and antibiotics, they maintained their short-circuit current (I(sc)) responses to glucose and theophylline for 48 h. Histological examination revealed a 50% diminution of villus height over 36 h but no change in crypts. Height was better maintained during a 36-h incubation of small intestine from SCID mice, suggesting a role for B or T lymphocytes in villus atrophy. Exposure of small intestine to 100 U/ml IFN-gamma for 36 h decreased basal I(sc) by 40% and I(sc) responses to glucose and theophylline by approximately 70%; at 1,000 U/ml for 36 h, IFN-gamma inhibited these I(sc) responses by 90%. An inhibitor of inducible NO synthase did not reverse these effects, suggesting that they are not mediated by NO. Tissue resistance, mucosal K(+) content, and epithelial morphology were not affected. Ouabain-sensitive ATPase activity in homogenates was inhibited 60% by IFN-gamma (100 U/ml for 36 h). IFN-gamma inhibition of I(sc) responses to glucose and theophylline also occurred in SCID mouse small intestine. Thus murine small intestinal sheets can be maintained viable in vitro for at least 48 h, although villus blunting develops (but less so in SCID mouse small intestine). Also, prolonged exposure to IFN-gamma downregulates Na(+)-coupled glucose absorption, active Cl(-) secretion, and Na(+)-K(+)-ATPase activity, effects unlikely to be mediated by enhanced NO.

Animals↗

PubMed2000

G8363A mutation in the mitochondrial DNA transfer ribonucleic acidLys gene: another cause of Leigh syndrome.

We identified a G-->A transition at nt-8363 in the mitochondrial DNA transfer ribonucleic acidLys gene in blood and muscle from a 13-month-old girl who had clinical and neuroradiologic evidence of Leigh syndrome and died at age 27 months. The mutation was less abundant in the same tissues from the patient's mother, who developed myoclonus epilepsy with ragged red fibers (MERRF) in her late 20s. In both mother and daughter, muscle histochemistry showed ragged red and cytochrome c oxidase-negative fibers and biochemical analysis showed partial defects of multiple respiratory-chain enzymes. A maternal half-sister of the proband had died at 2.5 years of age from neuropathologically proven Leigh syndrome. The G8363A mutation, which previously had been associated with cardiomyopathy and hearing loss, MERRF, and multiple lipomas, also should be included in the differential diagnosis of maternally inherited Leigh syndrome.

Adult↗

PubMed2000

Efficacy of postoperative blood salvage following total hip arthroplasty in patients with and without deposited autologous units.

BACKGROUND: Patients undergoing total hip replacement routinely receive perioperative blood transfusions, increasing their risk of blood-borne disease, isoimmunization, anaphylactic reaction, and hemolytic reaction. The purpose of this retrospective, case-control study was to evaluate the effect of postoperative blood salvage on the need for allogeneic transfusion following total hip replacement. METHODS: We reviewed the medical records of ninety consecutive patients who, during a twelve-month period, had undergone unilateral, elective total hip replacement that included use of a postoperative blood salvage device. For comparison, we reviewed the medical records of ninety consecutive patients who had undergone total hip replacement without postoperative blood salvage. Overall, 156 patients had complete medical records and were included in the study. RESULTS: Eight (10 percent) of the patients who had been treated with a drain and seventeen (23 percent) of the patients who had been treated without a drain received allogeneic transfusions. Of the nineteen patients who had not deposited autologous blood, all six without postoperative blood salvage required allogeneic transfusion. With control for other variables in the model, regression analysis showed a significantly increased risk of allogeneic transfusion among patients who had undergone total hip replacement without postoperative blood salvage (p = 0.0028) and without having predonated autologous units (p = 0.0001). CONCLUSIONS: Despite a limited sample size, the study results showed that postoperative blood salvage significantly reduced the risk of allogeneic transfusion among patients managed with total hip replacement, whether or not they had deposited autologous blood (p < 0.0001). With control for donated units, age, gender, preoperative hematocrit, intraoperative blood loss, and cementless technique, patients who were treated without postoperative blood salvage were approximately ten times more likely to require allogeneic transfusion than were patients who had a drain.

Adult↗

PubMed1999

Children with acute lymphoblastic leukemia who receive T-cell-depleted HLA mismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome.

Disparity for HLA in unrelated donor bone marrow transplantation (BMT) increases the risk of graft rejection and graft-versus-host disease (GVHD) and may compromise transplant outcome. We have compared the outcome of matched and mismatched transplants from unrelated donors in 137 children with acute lymphoblastic leukemia (ALL). Their disease status was complete remission (CR)-1, 24 patients; CR-2, 88 patients; CR-3, 18 patients; CR-4, 2 patients; and relapse, 5 patients. CAMPATH monoclonal antibodies were used for T-cell depletion and cyclosporin A was given to 134 children together with short-course methotrexate in 43, mainly when there was HLA disparity. Fifty-two donor/recipient pairs were HLA-mismatched, 41 at HLA-A and -B and 11 at HLA-DR and -DQ loci. Overall graft failure was increased in recipients of marrow mismatched at either HLA-A, -B, -DR, or -DQ (15.7% v 4.8%; P =.057) mainly because there was a higher proportion of children with primary graft failure (11. 8% v 1.2%; P =.012). The presence of an HLA-C locus mismatch did not independently increase the likelihood of graft failure. There was no significant difference in the incidence of acute GVHD >/= grade 2 between the matched and mismatched groups (P =.849). For patients in CR-2, the risk of relapse post-BMT was significantly lower if leukemic relapse occurred off-treatment (P =.005). The Kaplan-Meier overall and leukemia-free survival (LFS) estimates for recipients of matched and mismatched BMT, respectively, at 36 months were 49% versus 42% (P =.380) and 45% versus 40% (P =.654). Although HLA mismatching results in an increased occurrence of primary graft failure with T-cell-depleted allografts, it allows more donors to be identified rapidly for children with ALL without compromising overall transplant outcome.

Adolescent↗

PubMed1999

The characterization of macrophages and osteoclasts in tissues harvested from revised total hip prostheses.

The differentiation and maturation of macrophages and osteoclasts at the prosthetic interface in cases of implant loosening are poorly understood. Using histochemical and immunohistochemical staining methods, we compare macrophage differentiation in tissues from revised hip replacements in patients with specific clinical-radiological appearances. Periprosthetic tissues were harvested from 12 cemented acetabular and 12 cemented femoral components in 24 patients undergoing revision hip replacement. The prostheses were all radiographically and clinically loose. Six acetabular and six femoral components demonstrated radiographic ballooning osteolysis. Serial 6 microm frozen sections of the periprosthetic tissues were processed with hematoxylin and eosin for general tissue morphology, and analyzed for the presence of tartrate resistant acid phosphatase (TRAP, an osteoclast marker). Immunoperoxidase staining using monoclonal antibodies to CD68 (macrophages and osteoclasts) and CD51 (the alpha chain of the vitronectin receptor, an osteoclast marker) was also performed. Approximately 8-30% of the total cells in the tissues were positive for TRAP and the vitronectin receptor, and comprised a subset of the CD68 positive macrophages and macrophage polykaryons. However, there were no statistically significant differences between specific groups (femoral vs. acetabular, osteolysis vs. no osteolysis) for the numbers or percentages of macrophages or osteoclast-like cells. Once prosthetic loosening has occurred, few differences in the macrophage-osteoclast profile of tissues from different periprosthetic locations, with and without osteolysis, are noted. This suggests a final common biologic pathway for periprosthetic bone resorption, once implant loosening has transpired.

Acid Phosphatase↗

PubMed1999

Glutaryl-CoA dehydrogenase deficiency presenting as 3-hydroxyglutaric aciduria.

Two siblings who were found to have deficiency of glutaryl-CoA dehydrogenase were identified by the presence of large amounts of 3-hydroxyglutaric acid in the urine. Patients with this disease, termed glutaric acidemia or glutaric acidemia Type I, usually present with large amounts of glutaric acid in the urine, and amounts of 3-hydroxyglutaric acid found are less. Patients were ataxic and dystonic. Intelligence was normal. 3-Hydroxyglutaric acid in the urine was quantified by organic acid analysis via gas chromatography mass spectrometry (GCMS) and by stable isotope-dilution (internal standard) GCMS. Glutaryl-CoA dehydrogenase activity in cultured fibroblasts was found to be 2% of the control level. The nature of the mutations was identified, and both patients were found to be compound heterozygotes for R227P, which changed an arginine to a proline, and E365K, which changed a glutamate to a lysine.

Amino Acid Metabolism, Inborn Errors↗