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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
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↗
PubMed1995

Tissue ingrowth and differentiation in the bone-harvest chamber in the presence of cobalt-chromium-alloy and high-density-polyethylene particles.

Particulate wear debris from joint replacements has been implicated in the etiology of periprosthetic bone resorption. However, the effect of high-density-polyethylene or cobalt-chromium-alloy particles on osteoclastic bone resorption in vivo has not been studied previously, to our knowledge. Therefore, we examined the effect of these particles on tissue ingrowth, net bone formation (per cent trabecular bone), and osteoclastic bone resorption (osteoclasts per unit of bone surface) with use of a bone-harvest chamber that had a transverse one-millimeter channel for tissue ingrowth. After an initial six-week period for incorporation of the chamber into the proximal part of the tibia of rabbits, the contents of the channel were harvested repeatedly at three-week intervals. The carrier solution, 1 per cent sodium hyaluronate, was implanted first. In subsequent implantations, the hyaluronate was mixed with high-density-polyethylene or cobalt-chromium particles at concentrations of 10(8) particles per milliliter. The tissue harvested from the chambers that contained no particles was composed of longitudinally oriented trabecular bone in a fibrovascular stroma. Particulate high-density polyethylene evoked a moderate foreign-body reaction and a chronic inflammatory response and decreased net bone formation. When cobalt-chromium particles had been implanted, the tissue exhibited a more florid foreign-body reaction and a chronic inflammatory response, often in a nodular arrangement, in a background of dense connective tissue. Bone was sparse, and areas of cell necrosis and hyaline degeneration were noted. Histomorphometric analyses were carried out to determine the amount of net bone formation and osteoclastic bone resorption in the presence or absence of high-density-polyethylene or cobalt-chromium particles. The amount of bone was greatest in the control specimens, moderately decreased in the presence of high-density-polyethylene particles, and greatly decreased in the presence of cobalt-chromium particles. The number of osteoclasts in Howship lacunae per unit of trabecular bone surface was increased in the presence of high-density polyethylene, indicating that these particles stimulate osteoclastic bone resorption.

Animals↗
PubMed1995

Graft-versus-host-disease prophylaxis for matched unrelated donor bone marrow transplantation: comparison between cyclosporine-methotrexate and cyclosporine-methotrexate-methylprednisolone.

We performed a sequential study comparing two regimens, cyclosporine-methotrexate (CsA-MTX) and cyclosporine-methotrexate-methylprednisolone (CsA-MTX-MP) for graft-versus-host disease (GVHD) prophylaxis in patients undergoing matched unrelated donor bone marrow transplantation (MUD BMT). Study end-points were the development of GVHD, various infectious complications and survival. Twenty nine patients with malignant hematologic disease without HLA-compatible family donors were treated between May 1990 and November 1993. All donors were volunteers from the National Marrow Donor Program (NMDP) serologically HLA-A-A, B and DR identical. MLC reactivity and high resolution DR DNA typing were not used to exclude donors. Sixteen patients received CsA-MTX and 13 patients received CsA-MTX-MP. CsA and MTX doses were the same in both groups: CsA 1.5 mg/kg i.v. over 2h every 12h beginning the day prior to transplant (day-1) and MTX 10 mg/m2 i.v. bolus on days +1, +3 and +6 with leucovorin on days +2, +4 and +7. MP was administered at a dose of 0.25 mg/kg i.v. every 12h beginning on day +7 and increased to 0.5 mg/kg on day +14. Beginning on day +35 MP and CsA were tapered 5% per week with targeted discontinuation at 6 months. Both groups were comparable for primary disease, preparative regimen, recipient age (median 33 VS 33 years), donor age (median 39 vs 39.5 years), donor-recipient sex, donor ABO mismatch and serologic CMV positivity. All patients received similar supportive care.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Recombinant adeno-associated virus-mediated gene transfer into hematopoietic progenitor cells.

Recombinant adeno-associated viruses (rAAV) containing only the inverted terminal repeats (ITR) from the wild-type virus are capable of stable integration into the host cell genome, and expression of inserted genes in cultured cells. We have now defined the ability of rAAV to introduce genes into primary hematopoietic progenitors. A vector was constructed containing the coding sequences for beta-galactosidase (beta-gal), including a nuclear localization signal, under the control of a strong viral promotor. Infectious vector particles were prepared by cotransfection of the vector plasmid with a second plasmid that contained the coding sequences for AAV proteins into adenovirus-infected human embryonic kidney cells. These vector preparations transferred and expressed the beta-gal gene in human K562 erythroleukemia and Detroit 6 cells. Positive immunoselection yielded a population of enriched CD34+ cells that were transduced with the rAAV beta-gal vector. Nuclear localized enzyme expression was documented in 60% to 70% of infected cells. Progenitor-derived colonies that developed after 2 weeks in clonogenic cultures were shown to have viral-associated DNA at an estimated copy number of 1 to 2 per cell using a semiquantitative polymerase chain reaction (PCR) method. Integration of AAV into hematopoietic progenitors was documented using wild-type virus, as its genome may integrate at a preferred site on chromosome 19. Our data suggest that rAAV will transfer and express genes in primitive hematopoietic progenitors with high frequency, and support the development of this vector system for therapeutic gene transfer.

Adenoviruses, Human↗
PubMed1994

An essential role for HLA-DM in antigen presentation by class II major histocompatibility molecules.

In antigen-presenting cells, class II molecules of the major histocompatibility complex (MHC) bind peptides derived from endocytosed proteins. In certain B-lymphoblastoid cell mutants, MHC class II molecule-peptide complex formation is impaired, resulting in deficient antigen-presenting function. MHC deletion mutants with this defect map the responsible gene(s) to the class II region of the MHC. Here we report that multiple independent mutants with the class II presentation defect harbour lesions in HLA-DMB, an MHC-linked gene encoding a class II-like beta-chain. Expression of DMB complementary DNA in mutants lacking DMB messenger RNA restores the wild-type phenotype. These results establish HLA-DM as a critical regulatory molecule in class II-restricted antigen presentation and suggest that it functions at an intracellular site to promote class II molecule-peptide association.

Animals↗
PubMed1994

A mutant human histocompatibility leukocyte antigen DR molecule associated with invariant chain peptides.

From a human histocompatibility leukocyte antigen (HLA)-DR/DQ hemizygous, B lymphoblastoid progenitor, we isolated a cell line, 10.24.6, with a DR alpha missense mutation (96P-->96S), which results in an N-linked carbohydrate addition at position 94 in the DR alpha 2 domain. Several features of 10.24.6 cells suggest that the mutation disrupts normal intracellular formation of peptide/DR complexes. The mutant HLA-DR dimers, though expressed at the cell surface, lack the conformation of the mature, peptide-loaded class II molecules of the progenitor cell, as assessed by their loss of binding of certain antibodies and by the lack of stability in detergent (sodium dodecyl sulfate) solution. In addition, presentation of endocytosed antigen to HLA-DR-restricted T cells is defective in the mutant, but can be restored by transfection of a wild type DRA gene. Assays with synthetic peptides indicate that the 10.24.6 phenotype is not due to an intrinsic inability of the mutant DR molecules to bind peptides. Therefore, to directly evaluate peptide occupancy of the mutant molecules, we analyzed acid-eluted, HLA-DR-associated peptides. The predominant species from the 10.24.6 mutant is a nested set of invariant chain (Ii)-derived peptides that are undetectable in the DR eluate from progenitor cells. The region of DR alpha altered in the mutant molecules is thus implicated in normal formation of peptide/DR complexes. Further, the same set of Ii peptides associated with the DR molecules is present in the eluate from an antigen presentation mutant with a defect in an major histocompatibility complex (MHC)-linked gene. These results suggest that DR molecules in 10.24.6 and in certain presentation mutants are affected at the same or related steps in class II molecule biosynthesis, raising the possibility that class II molecules interact with an MHC-encoded accessory molecule during antigen presentation.

Amino Acid Sequence↗
PubMed1994

Primary breast lymphoma with skin involvement arising in lymphocytic lobulitis.

Primary breast lymphoma is a rare tumour which has recently been associated with pre-existing lymphocytic lobulitis. We report a patient with lymphocytic lobulitis in whom the lymphoma recurred in the contra-lateral breast 5 years after the initial presentation, to be followed shortly afterwards by skin involvement. This progression illustrates the relationship between extra-nodal lymphomas and underlying autoimmune disease and the homing of lymphomas to related sites.

Breast Neoplasms↗
PubMed1994

Blood pressure control and erythrocytosis in rats: theory and observations.

We compared some of our latest experiments on blood pressure control and erythrocytosis in spontaneously hypertensive rats with Gaar's computer-simulated studies, which suggest that erythrocytosis is a key to understanding the hemodynamic changes in hypertension. We tested two of Gaar's several predictions: (i) peripheral vascular resistance decreases when the feedback control of erythrocytosis is blocked and (ii) in primary hypertension, blood volume is increased slightly. We also studied the interrelation of systolic blood pressure and plasma renin substrate in spontaneously hypertensive rats, and the effect of diet on renin, blood pressure, and erythrocytosis. Our data showed that (i) on a percentage basis the renin system supports blood pressure essentially in the same manner in normal and hypertensive rats, (ii) peripheral vascular resistance decreased when erythrocytosis was partially blocked by feeding a low-iron diet, (iii) blood volume was similar in normal and hypertensive rats, and (iv) dextrin stimulates plasma renin, packed cell volume, and blood pressure in hypertensive rats. We conclude that blood pressure and erythrocytosis are interrelated, that the combined data of stimulated and experimental studies support the notion that primary hypertension is a blood-vessel adaptation in response to a renal energy need that may require additional oxygen.

Aging↗
PubMed1994

Oxygen therapy using pulse and continuous flow with a transtracheal catheter and a nasal cannula.

Pulse delivery (PD) of oxygen was compared with continuous flow (CF) utilizing transtracheal oxygen catheter (TTO) and nasal cannula (NC) in 20 stable patients with chronic hypoxemia. Oxygen saturation, respiratory rate, and accuracy of pulsed oxygen delivery were measured during sleep studies and these parameters, as well as arterial blood gases, were evaluated during rest and exercise. Additionally, bulk liquid oxygen use was measured under each condition, for a period of 1 month. Pulse delivery NC was evaluated in six subjects, CF NC in 14 subjects, and PD and CF TTO in 20 subjects over the 1-month period. Results showed that, as a group, patients were adequately oxygenated when utilizing the PD with both NC and TTO as assessed by arterial blood gases, oximetry, and hematocrit. However, four subjects could not be adequately oxygenated on PD NC during exercise even at the maximum liter per minute setting and could not be studied with this mode of therapy. The PD settings in the remaining subjects were equivalent to continuous flow settings for TTO and NC as assessed by PaO2 for rest and SaO2 for exercise and sleep. Compared with standard CF NC, the daily bulk oxygen use was decreased by 29.4 percent with CF TTO, by 48.2 percent with PD NC, and by 49.9 percent with PD TTO. We conclude that, compared with CF NC, PD of oxygen via TTO or NC by this method appears to be a safe, reliable, effective, and cost-effective method of oxygen delivery in the majority of subjects when used with proper screening.

Aged↗
PubMed1994

T-lymphocytes are not necessary for particulate polyethylene-induced macrophage recruitment. Histologic studies of the rat tibia.

Immunological processes involving T-lymphocytes have been implicated in the mechanisms of aseptic loosening of joint endoprostheses. We report the histological reaction of bone to phagocytosable particles of high-density polyethylene (HDPE) in normal and T-cell deficient rats. A bolus of 3 x 10(7) polyethylene particles averaging 4.7 microns in size, mixed in 0.1 mL of sodium hyaluronate, was injected into the right proximal tibia of 10 normal and 10 T-cell deficient (nude) Rowett rats from the same litter. The left control side was injected with sodium hyaluronate alone. The animals were killed after 6 weeks. Transverse paraffin-embedded sections stained with hematoxylin and eosin were made of the implant area. On the control side, there was normal bone marrow without evidence of foreign body reaction. On the HDPE side, in both normal and T-cell deficient rats, macrophages were found to surround and engulf the particles, with no differences in the histological reactions. We conclude that T-lymphocytes are not necessary for the recruitment of macrophages to sites in which phagocytosable particles of HDPE have been implanted.

Animals↗
PubMed1994

Bone formation in the presence of phagocytosable hydroxyapatite particles.

Small particles of biomaterials used in orthopaedic surgery have been shown to induce the resorption of bone. The purpose of this study was to determine whether phagocytosable particles of hydroxyapatite had an adverse effect on bone ingrowth. Bone harvest chambers were implanted bilaterally in the proximal tibial metaphyses of 13 mature rabbits. The bone harvest chamber 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 bone harvest chambers, the contents of the canal were harvested at 3-or 6-week intervals. Hydroxyapatite particles (diameter, 5 mu) were mixed with a carrier solution, 1% sodium hyaluronate, and implanted in the canal of one chamber in each animal. The contralateral chamber was implanted with the carrier only and served as a control. Histological sections from the tissue harvested from the chambers were evaluated by light microscopy and histomorphometry, and the area of bone ingrowth was measured as a percentage of total area in each section. At 3 weeks there was more bone in the hydroxyapatite sections than in controls; at 6 weeks there was no difference. Hydroxyapatite particles were incorporated within the matrix of new ingrown bone at both time periods. There was no evidence of granuloma formation or inflammation. Previous studies have shown that particles of high density polyethylene and bone cement adversely affect bone ingrowth in this model. The present results suggest that hydroxyapatite particles, small enough to be phagocytosed by macrophages, did not have such effects.

Animals↗
PubMed1993

Ingrowth of bone into pores in titanium chambers implanted in rabbits: effect of pore cross-sectional shape in the presence of dynamic shear.

The micromotion chamber consists of a titanium outer cylinder and a central core, which are pierced by a transverse 1-mm canal for tissue ingrowth. Six weeks after implantation in the proximal tibia in mature rabbits, the outer cylinder is osseointegrated; the central core can then be moved in relation to the fixed outer cylinder. Thus, the tissue growing through the pore, from the cylinder into the core, can be subjected to motion of a predetermined amplitude and frequency. In this study we investigate the influence of pore cross-sectional shape on tissue ingrowth in the canal. In six animals, the outer cylinder was pierced by a square 1-mm hole that was congruent with the square hole in the core; in five animals, the hole in the cylinder was round. The cross-sectional area of the square hole in the cylinder was about 21% greater than in a round hole. In all cases, the channel in the inner core was 1 x 1 x 5-mm quadrate. All chambers underwent 20 cycles/day of micromotion for a 3-week period. The amplitude of the micromotion was 0.5 mm. Chambers containing cylinders with a round hole demonstrated less bone ingrowth as compared to cylinders with a square hole. This observation may be due to several factors including the greater cross-sectional area of the square versus the round hole in the cylinder and the enhanced congruity provided by the square outer and inner holes, versus a round outer and square inner hole.

Animals↗
PubMed1993

Difference in bone ingrowth after one versus two daily episodes of micromotion: experiments with titanium chambers in rabbits.

Mechanical stimulation has been shown to affect the differentiation and development of mesenchymal tissue. In the present study, we compared the histological and histomorphometric results of tissue ingrowth into micromotion chambers that were moved at 0 cycles per day, 20 cycles once per day, and 20 cycles twice per day over 20-30 sec, for 3 weeks. In each case, a chamber having a 1 x 1 x 5 mm square-holed groove for tissue ingrowth was used. The total amplitude of motion was 0.75 mm. Histological sections from nonmoved chambers contained extensive trabecular bone, embedded in a fibrovascular stroma. Histomorphometric analysis disclosed that bone comprised a mean of 31 +/- 2% (mean +/- SEM) of the ingrown tissue. Twenty movements per day appeared to further stimulate bone ingrowth (46 +/- 5%). Extensive ingrowth of more immature woven and trabecular bone was noted in a more cellular stroma. In general, increasing the degree of micromotion to 20 movements twice per day resulted in a decreased amount of bone formation (19 +/- 7%). In several of these specimens, little or no bone could be found. These experiments have demonstrated that, for the parameters chosen in this study, a short daily period of low frequency, micromotion may facilitate bone ingrowth; however, when the same motion is delivered twice daily, bone ingrowth is depressed. Thus a "window" of externally applied strain appears to exist, which may facilitate or discourage tissue differentiation to bone.

Animals↗
PubMed1993

Localization of beta 1-integrins in human cartilage and their role in chondrocyte adhesion to collagen and fibronectin.

In the past, proteins have been described that may be involved in chondrocyte interactions with extracellular collagen, but little is known about the role of integrins in chondrocyte-collagen interactions. Here we report on the analysis of beta 1-integrin distribution in human fetal cartilage and on the expression of integrins on fetal chondrocytes, using monoclonal and polyclonal antibodies to integrin alpha- and beta-chains. We show the presence of alpha 2-, alpha 5-, alpha 6-, alpha v-, and beta 1-chains on freshly isolated chondrocytes by surface immunofluorescence in the fluorescence-activated cell sorter and by surface iodination followed by immunoprecipitation. Affinity chromatography of bovine chondrocyte membrane proteins on a collagen-Sepharose column followed by immunoprecipitation confirmed the presence of the collagen-binding alpha 2 beta 1-integrin on chondrocytes. Chondrocyte adhesion on native collagens I and II, on fibronectin, and on laminin was completely blocked by anti-beta 1; anti-alpha 2 reduced chondrocyte binding to collagen by only 40-50%; similarly, anti-alpha 1-antibodies were also able to reduce chondrocyte binding to collagen, although alpha 1 could not be unequivocally identified on chondrocytes. Chondrocyte adhesion to fibronectin was Mg(2+)- and Ca(2+)-dependent and could be inhibited by anti-alpha 5 and by RGD peptides. Chondrocyte adhesion to native collagens is Mg(2+)-, but not Ca(2+)-dependent and RGD-independent. Interestingly, although these data point to a role of alpha 2 beta 1 in chondrocyte-collagen interactions in vitro, alpha 2 could not be visualized in sections of human fetal cartilage, in contrast to the beta 1-, alpha v-, and alpha 5-chains which were present. This suggests that alpha 2 beta 1-integrin may be involved in the assembly of a pericellular collagen matrix in vitro, but may not be required for chondrocyte-collagen interactions in intact cartilage.

Animals↗
PubMed1993

Effects of mechanical stimulation on the differentiation of hard tissues.

In 1892, J.L. Wolff believed that bone was a dynamic organ that responded to the biomechanical environment. Research has shown that mechanical stimulation can have a profound effect on the differentiation and development of mesenchymal tissues. It would appear that a 'window' of mechanical strain exists which may facilitate or discourage the accretion of bone. With respect to processes such as fracture healing and ingrowth of bone into porous coated prostheses, it may be possible to modulate the mechanical environment with the application of well-defined, exogenous loads in order to promote a more favourable outcome.

Animals↗