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Biomedical subjects

S Goodman

Publications and source records attributed to S Goodman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Different effects of phagocytosable particles during bone formation versus remodeling.

Previously, small phagocytosable particles of high density polyethylene (HDPE) but not Ti6-Al4-V alloy, at a concentration of 10(8) particles/mL inhibited net bone formation in vivo after 3 weeks in the bone harvest chamber (BHC). These findings reflected the effects of particles during the phase of bone ingrowth. In this study, we tested whether these effects persisted or were different during the phase of bone maturation and remodeling. BHCs were bilaterally implanted in mature male NZW rabbits. After a 6-week period for osseointegration, the contents of the chamber were harvested and discarded. One percent sodium hyaluronate, the carrier, was then placed within the canal of the chambers bilaterally and the tissue within the chambers was harvested 3 weeks later. HDPE particles were then inserted unilaterally for a 3-week period, followed by Ti6-Al4-V for 3 weeks, HDPE for 6 weeks, and Ti6-Al4-V for 6 weeks. The side chosen for each treatment was switched consecutively; the nonimplanted, contralateral chamber served as a control. At 3 weeks the control treatments yielded trabeculae of woven bone in a fibrovascular stroma. By 6 weeks, the peripheral trabeculae were thicker, and a central marrow cavity was developing. Bone ingrowth was less with HDPE particles at 3 and 6 weeks compared to controls. Ti6-Al4-V particles did not inhibit bone ingrowth at 3 weeks but showed a trend at 6 weeks. The characteristics of particles affect the differentiation, maturation, and remodeling of mesenchymal tissue differently.

Alloys↗
PubMed1996

Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission.

Allogeneic sibling bone marrow transplantation (BMT) is the recommended treatment for relapsed childhood acute lymphoblastic leukaemia (ALL), but appropriate donors are only available in 30% of cases. Unfortunately, BMT from unrelated donors (UD) has been associated with high rates of severe graft-versus-host disease (GvHD) and transplant-related mortality (TRM). In an attempt to improve outcome in UD-BMT we have assessed the impact of T-cell depletion using CAMPATH-1 (anti-CD52) monoclonal antibodies in 50 consecutively referred patients with relapsed ALL in second remission. All were previously treated according to MRC protocols UKALL X and XI, and then given chemotherapy on MRC R1 from relapse until UD-BMT, 19 patients had relapsed on and 31 off therapy. Patients and donors were fully matched at HLA-A, -B, -DR and -DQ loci in 29 cases and mismatched in 21 (four mismatched for more than one antigen). Pre-transplant conditioning comprised CAMPATH-1G, cyclophosphamide and total body irradiation. Bone marrow was T-cell depleted in vitro using CAMPATH-1 antibodies. Additional GvHD prophylaxis consisted of cyclosporin A (42 cases), cyclosporin plus methotrexate (four) or none (four). 47 patients engrafted. The incidence of acute GvHD was very low: two patients with grade II disease in the matched group, four with grade II-IV in the mismatched group. Only four patients have chronic GvHD. The actuarial event-free survival (EFS) at 2 years is 53%, with no significant difference between the matched and mismatched group. Further leukaemic relapse was the most important cause of failure. These results are similar to the most favourable published reports for HLA-matched sibling BMT in relapsed ALL.

Acute Disease↗
PubMed1996

Worldwide patterns of mitochondrial DNA differentiation in the harbor seal (Phoca vitulina).

The harbor seal (Phoca vitulina) has one of the broadest geographic distributions of any pinniped, stretching from the east Baltic, west across the Atlantic and Pacific Oceans to southern Japan. Although individuals may travel several hundred kilometers on annual feeding migrations, harbor seals are generally believed to be philopatric, returning to the same areas each year to breed. Consequently, seals from different areas are likely to be genetically differentiated, with levels of genetic divergence increasing with distance. Differentiation may also be caused by long-standing topographic barriers such as the polar sea ice. We analyzed samples of 227 harbor seals from 24 localities and defined 34 genotypes based on 435 bp of control region sequence. Phylogenetic analysis and analysis of molecular variance showed that populations in the Atlantic and Pacific Oceans and east and west coast populations of these oceans are significantly differentiated. Within these four regions, populations that are geographically farthest apart generally are the most differentiated and often do not share genotypes or differ in genotype frequency. The average corrected sequence divergence between populations in the Atlantic and Pacific Oceans is 3.28% +/- 0.38% and those among populations within each of these oceans are 0.75% +/- 0.69% and 1.19% +/- 0.65%, respectively. Our results suggest that harbor seals are regionally philopatric, on the scale of several hundred kilometers. However, genetic discontinuities may exist, even between neighboring populations such as those on the Scottish and east English coasts or the east and west Baltic. The mitochondrial data are consistent with an ancient isolation of populations in both oceans, due to the development of polar sea ice. In the Atlantic and Pacific, populations appear to have been colonized from west to east with the European populations showing the most recent common ancestry. We suggest the recent ancestry of European seal populations may reflect recolonization from Ice Age refugia after the last glaciation.

Animals↗
PubMed1996

Etoposide and mitoxantrone as a second cycle of consolidation therapy following high dose cytosine arabinoside and daunorubicin in patients with acute non-lymphocytic leukemia in remission: a pilot study.

High dose cytosine arabinoside (ARA-C) has produced long term relapse free survival in 26% to 49% of patients when used as consolidation therapy of acute non-lymphocytic leukemia (ANLL) in first remission. However, the optimal consolidation regimen has not been defined. In this pilot study we attempted to confirm and extend our previous studies of high dose consolidation therapy by administering two cycles of consolidation chemotherapy to patients with ANLL in first remission. The first cycle was high dose ARA-C 3 gm/m2 over 1 hour every 12 hours for 12 doses followed by daunorubicin 45 mg/m2/day for three days. The second cycle was etoposide 75 mg/m2/day for 10 days and mitoxantrone 12 mg/m2/day for three days. Twenty-three patients received high dose consolidation chemotherapy, 13 of whom received the proposed two cycles. The major reason for not receiving the planned second consolidation cycle was life threatening toxicity, primarily fungal infection, during the first consolidation cycle. By actuarial estimate, 46% of patients receiving consolidation chemotherapy were projected to be relapse free at 36 months. There were no deaths during consolidation. Survival was not improved in patients receiving etoposide and mitoxantrone as the second cycle of consolidation therapy as compared to patients receiving only one cycle of consolidation therapy.

Adult↗
PubMed1996

Polyethylene and titanium alloy particles reduce bone formation. Dose-dependence in bone harvest chamber experiments in rabbits.

Particles similar to those generated from joint replacements affect net bone formation within the Bone Harvest Chamber in rabbits. Whether these effects depend on the concentration of particulate materials is unknown. In this study, we performed a histomorphologic and morphometric analysis of net bone formation in the Bone Harvest Chamber in the presence of different concentrations of phagocytosable particles of high density polyethylene and titanium 6-aluminum 4-vanadium alloy. Chambers were implanted in 9 mature New Zealand white rabbits bilaterally. Concentrations of 10(6), 10(7) and 10(8) polyethylene particles/mL, and 10(8) and 10(9) particles/ mL of titanium alloy in 1% sodium hyaluronate carrier were implanted for 3-week periods in sequence in each of the chambers. 3-week control periods in which nothing was implanted in the chamber were included between the treatments. Increasing concentrations of polyethylene particles were associated with a more marked foreign body response and fibrosis. Net bone formation for the three polyethylene doses was reduced by 11%, 21% and 33% of controls, respectively. For titanium alloy, net bone formation was reduced by 8% and 56% of controls, for concentrations of 10(8) and 10(9) particles/mL, respectively. Our findings suggest possible adverse effects of wear debris on net bone formation and bony remodeling in the prosthetic bed, when concentrations of specific particles reach critical local levels.

Alloys↗
PubMed1996

PROTECT (Prospective Reinfarction Outcomes in the Thrombolytic Era Cardizem CD Trial): a randomized, double-blind clinical trial of diltiazem versus atenolol in secondary prophylaxis post non-Q wave myocardial infarction.

OBJECTIVE: To describe the rationale and design of the Prospective Reinfarction Outcomes in the Thrombolytic Era Cardizem CD Trial (PROTECT). DESIGN: A multicentre, randomized, double-blind, parallel-group comparison of once daily beta-therapy versus heart rate lowering calcium channel blocker therapy, in the reduction of one-year nonfatal reinfarction and cardiovascular death (combined primary end-point) initiated 24 to 96 h post non-Q wave myocardial infarction. SETTING: One hundred and twenty hospitals across Canada. PATIENTS: Over 7500 women and men aged 21 years or older with enzyme-confirmed non-Q wave infarction and without significant left ventricular systolic dysfunction will be recruited over two years. INTERVENTIONS: Once daily beta-blocker therapy (oral atenolol, 50 to 200 mg) versus once daily calcium channel blocker therapy (oral diltiazem 120 to 360 mg) with follow-up for up to three years. CONCLUSIONS: The PROTECT will be the largest all-Canadian cardiovascular trial to date and will compare two commonly prescribed agents for secondary prophylaxis following non-Q wave infarction. The scientific question addressed by the PROTECT is of major public health importance and the results of the study will directly affect current clinical practice.

Adrenergic beta-Antagonists↗
PubMed1995

Mutational analysis of two DR alpha residues involved in dimers of HLA-DR molecules.

Crystallographic analysis of HLA-DR1 molecules reveals a "dimer of dimers" with two reciprocal salt bridges between Glu 88 and Lys 111 of the two DR alpha chains. To determine whether these amino acids are critical for Ag presentation, we generated a panel of human B cell transfectants expressing DR alpha chains with mutations at residues 88, 111, or both. The mutant DR alpha chains, paired with endogenous DR3 beta chain, form cell surface dimers that retain epitopes recognized by a panel of anti-DR3 Abs. Replacement of Glu 88 with Ala (88A) selectively eliminates the ability to activate an alloreactive (anti-DR3) T cell clone. Mutant DR molecules with Lys substituted for Glu 88 (88K) fail to activate an alloreactive, an Ag-specific, and a peptide-specific T cell line. The DR alpha 88 mutants bind an exogenously supplied DR3-specific peptide and the mutant DR molecules migrate as dimers on SDS-PAGE, implying that their defective Ag presentation is not due to an inability to bind antigenic peptides. In contrast, substitution of Lys 111 with either Ala (111A) or Glu (111E) does not abrogate Ag presentation. Further, the defect introduced by Glu 88 to Lys mutation (88K) is not overcome by compensatory Lys to Glu mutation at position 111 (111E). Taken together, these results indicate an important functional or structural role for position 88 of the DR alpha chain, but argue against a requirement for interaction between DR alpha 88 and 111 during Ag-specific T cell stimulation.

Antigen Presentation↗
PubMed1995

Test-retest reliability of the Diagnostic Interview Schedule for Children (DISC 2.1). Parent, child, and combined algorithms.

BACKGROUND: Previous research has not compared the psychometric properties of diagnostic interviews of community samples and clinically referred subjects within a single study. As part of a multisite cooperative agreement study funded by the National Institute of Mental Health, 97 families with clinically referred children and 278 families identified through community sampling procedures participated in a test-retest study of version 2.1 of the Diagnostic Interview Schedule for Children (DISC 2.1). METHODS: The DISC was separately administered to children and parents, and diagnoses were derived from computer algorithms keyed to DSM-III-R criteria. Three sets of diagnoses were obtained, based on parent information only (DISC-P), child information only (DISC-C), and information from either or both (DISC-PC). RESULTS: Test-retest reliabilities of the DISC-PC ranged from moderate to substantial for diagnoses in the clinical sample. Test-retest kappa coefficients were higher for the clinical sample than for the community sample. The DISC-PC algorithm generally had higher reliabilities than the algorithms that relied on single informants. Unreliability was primarily due to diagnostic attenuation at time 2. Attenuation was greatest among child informants and less severe cases and in the community sample. CONCLUSIONS: Test-retest reliability findings were consistent with or superior to those reported in previous studies. Results support the usefulness of the DISC in further clinical and epidemiologic research; however, closely spaced or repeated DISC interviews may result in significant diagnostic attenuation on retest. Further studies of the test-retest attenuation phenomena are needed, including careful examination of the child, family, and illness characteristics of diagnostic stability.

Adolescent↗
PubMed1995

Treatment of silent ischemia in unstable angina: a randomized comparison of sustained-release verapamil versus metoprolol.

Silent ischemia is a frequent finding in patients with unstable angina and portends a poor prognosis. We compared the efficacy of sustained-release (SR) verapamil and metoprolol in reducing silent ischemia in patients with unstable angina and assessed whether detection of silent ischemia was related to unfavorable outcomes in the contemporary setting of concurrent therapy with heparin and aspirin. Holter monitoring (leads a VF, V2, V5) for the first 72 h was used to assess the frequency and duration of ST-shift episodes. There were 37 patients in the verapamil-SR group and 40 patients in the metoprolol group, with both groups having similar baseline characteristics. There were more episodes of angina in the verampamil-SR group (29 vs. 12, p = 0.05). There was no difference between the two groups in the frequency (51 vs. 49 episodes, p = 0.9) or duration (23 +/- 48 vs. 18 +/- 50 min, p = 0.6) of ST-shift episodes. There were 20 unfavorable in-hospital outcomes distributed equally between the two groups (p = 0.9). Patients with unfavorable outcomes had ST shift more often (50 vs. 28%, p = 0.07) and for a longer duration (40 +/- 69 vs. 13 +/- 38 min, p = 0.03). Patients with ST shift > or = 60 min had a 60% probability of unfavorable outcome compared with 33% for ST shift of 1-59 min duration and 20% for no ST shift (p = 0.04). We conclude that metoprolol appears to reduce symptoms better than verapamil-SR, but no difference in silent ischemia or unfavorable outcomes was seen. Silent ischemia remains a common occurrence in these patients despite heparin and aspirin therapy and its detection continues to have prognostic value.

Adrenergic beta-Antagonists↗
PubMed1995

Effects of particulate high-density polyethylene and titanium alloy on tissue ingrowth into bone harvest chamber in rabbits.

The purpose of this study was to determine whether small, phagocytosable particles of titanium alloy (Ti) and high-density polyethylene (HDPE) have an adverse effect on bone ingrowth. The bone harvest chamber (BHC) was implanted bilaterally in the proximal tibial metaphysis of six mature rabbits. The BHC has a transverse 1-mm wide pore providing a continuous canal through the chamber for tissue ingrowth. After an initial 6-week period for osseointegration of the BHC, the contents of the canal were harvested repeatedly at 3 weekly intervals. This could be done with the chamber in place, without disturbing its exterior surface or the surrounding bone. The carrier solution, 1% sodium hyaluronate (Healon) was implanted first. In subsequent implantations, Healon was mixed with particles of HDPE or Ti averaging 4.7 +/- 2.1 and 3.0 +/- 2.6 microns, respectively. The contralateral chamber was left empty and served as a control. The chambers were harvested repeatedly, alternating experimental and control sides. The sections from the control side, and those containing Healon alone demonstrated extensive trabecular bone in a fibrovascular stroma. The sections containing Ti alloy particles were qualitatively and quantitatively similar to the control sections and those containing Healon, except for the presence of small black granules of Ti alloy, dispersed in the fibrovascular stroma or phagocytosed by scattered macrophages. The sections containing HDPE particles were infiltrated and engulfed by mononuclear and multinuclear histiocytic cells in a highly fibrous stroma. The majority of the multinucleated cells present were interpreted as being foreign body giant cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloys↗
PubMed1995

Intermittent micromotion and polyethylene particles inhibit bone ingrowth into titanium chambers in rabbits.

We performed a histomorphological and morphometric analysis of the effects of short daily periods of micromotion and phagocytosable particles of high density polyethylene (PE) on bone ingrowth into a 1 x 1 x 5 mm canal within a titanium chamber in rabbits. The micromotion chamber (MC) was implanted in the tibia of nine mature New Zealand white rabbits. After osseointegration and first harvest of tissue, 40 micromotions (amplitude = 0.5 mm) were applied daily at a rate of 1 Hz for a 3-week period. The tissue within the chamber was then harvested. For the second treatment, PE particles (10(8)/mL) were placed within the canal. The tissue in the chamber was harvested 3 weeks later. The next treatment was a 3-week rest period, in which neither micromotion nor particles were utilized; a harvest followed. The final treatment combined PE particles and micromotion, followed by a harvest 3 weeks later. Sections from control harvests contained extensive trabecular bone arranged longitudinally throughout the canal in a fibrovascular stroma. Micromotion produced longitudinally oriented fibrous tissue within the chamber. PE particles were associated with macrophages, surrounding and engulfing the birefringent particles. The combination of particles and micromotion produced a fibrous stroma laden with macrophages. PE particles and micromotion, alone or together, produced a similar effect in inhibiting bone ingrowth, compared to nonmoved chambers without particles. In this short-term experiment, no additive or potentiating effect of these two stimuli could be demonstrated.

Animals↗
PubMed1995

Oxford meniscal bearing knee versus the Marmor knee in unicompartmental arthroplasty for arthrosis. A Swedish multicenter survival study.

In the Swedish Knee Arthroplasty Study, all 699 Oxford meniscal bearing cemented unicompartmental prostheses (Biomet, Bridgend, UK) were identified and analyzed regarding failure pattern and compared with all Marmor prostheses (Smith & Nephew Richards, Orthez, France) and with a time-, age-, and sex-matched subset of Marmor prostheses using survival statistics expressed as cumulative revision rates. After 1 year there was already a higher rate, and after 6 years the rate of the Oxford group was more than twice that of the Marmor group. There were 50 revisions in the Oxford group: dislocating meniscus in 16, loosening of the femoral component in 6, tibial component in 4, both components in 4, contralateral arthrosis in 10, infection in 4, and technical failure with instability, pain, and/or impingement of the meniscal bearing anterior in the femoral condyle in 6. It is still unclear if the design with the sliding menisci will, in the long turn, reduce wear and loosening, thereby compensating for the initially inferior results. It is recommended that until this question is clarified, the Oxford knee should be used on a limited scale for long-term comparative studies only.

Adult↗
PubMed1995

Malignant external otitis due to Aspergillus flavus with fulminant dissemination to the lungs.

Malignant external otitis secondary to aspergillus infection is rare, and only 10 cases have been reported in the literature. Nine of 10 patients responded to therapy and survived their infection. There have been no previous reports of dissemination of Aspergillus species from the ear to other organs. We describe a case of malignant external otitis due to Aspergillus flavus that disseminated hematogenously to the lungs. The result was an overwhelming, miliary pulmonary infection, which progressed very rapidly to respiratory failure and death. Pathological examination of lung tissue revealed multiple microabscesses and hyphal elements that had invaded the lung parenchyma from small pulmonary arteries.

Adult↗
PubMed1995

Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation.

PURPOSE: Hemorrhagic cystitis (HC) after bone marrow transplantation (BMT) has been ascribed to cyclophosphamide metabolites. HC has also been associated with excretion of the BK type of polyomavirus. The relative contributions of cyclophosphamide metabolites and BK virus in the development of HC following BMT are unknown. PATIENTS AND METHODS: We conducted a randomized trial to compare mesna with forced diuresis for prophylaxis against HC in 147 BMT recipients. We studied the association of BK virus with HC in 95 consecutive BMT recipients by prospectively monitoring urinary excretion of BK virus using polymerase chain reaction amplification of viral gene sequences. RESULTS: HC occurred in 37 of 147 (25.2%) transplant recipients. The incidence of HC was similar in patients given mesna (26.8%, 19 of 71) or forced diuresis (23.7%, 18 of 76), and in recipients of allogeneic (27.2%, 18 of 64) or autologous marrow (22.9%, 19 of 83). The incidence of HC was unrelated to primary disease, preparative regimen, or occurrence of graft-versus-host disease (GVHD). Excretion of BK virus was demonstrated in 50 of 95 patients (52.6%); 38 patients (40%) had persistent BK viruria (> or = two consecutive positive samples). HC occurred in 19 of 38 patients (50%) with persistent BK viruria, in one of 12 (8.3%) with only a single urine sample positive for BK virus, and in none of 45 who did not excrete BK virus (P < .0001). Shedding of BK virus also had a strong temporal correlation with onset of HC (r = .95). CONCLUSION: Mesna and forced diuresis are equally effective in abrogating the urothelial toxicity of preparative regimens for BMT. Since HC after BMT is virtually always associated with persistent BK viruria, strategies aimed at the prevention or elimination of viruria in BK seropositive recipients are warranted.

Adult↗