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Biomedical subjects

M Lind

Publications and source records attributed to M Lind.

At least 55 records · Page 3Linked to original sources
PubMed1997

Resorption of hydroxyapatite and fluorapatite coatings in man. An experimental study in trabecular bone.

The clinical use of hydroxyapatite (HA) coating is controversial especially in regard to the long-term performance of the coating and the effects of resorption. In each of 15 consenting patients we inserted two implants, coated with either HA or fluorapatite (FA) into the iliac crest. They were harvested at a mean of 13.6 +/- 0.6 months after surgery. Histological examination showed that bone ongrowth on the HA-coated implants was significantly greater (29%) than that on the FA-coated implants. When bone was present on the coating surface the HA coating was significantly thicker than the FA coating. When bone marrow was present, the HA coating was significantly thinner than the FA coating. The reduction in coating thickness when covered by bone or bone marrow was 23.1 +/- 9.7 microm for HA and 5.1 +/- 1.7 microm for FA (p < 0.01) suggesting that FA is more stable than HA against resorption by bone marrow. The findings suggest that in man the osteoconductive properties of HA coating are superior to those of FA. Resorption rates for both coatings were approximately 20% of the coating thickness per year. Bone ongrowth appears to protect against resorption whereas bone marrow seems to accelerate resorption. No adverse reaction was seen in the surrounding bone.

Apatites↗
PubMed1997

Improved fixation of porous-coated versus grit-blasted surface texture of hydroxyapatite-coated implants in dogs.

We inserted, in 8 dogs, implants with either porous-coated or grit-blasted titanium surface and coated with hydroxyapatite (HA) into trabecular bone in the proximal humerus, using a 1 mm gap model. After 25 weeks, push-out tests showed that energy absorption for porous-coated implants was twice that of grit-blasted implants, whereas shear stiffness was reduced by one fifth, indicating a stronger fixation of porous-coated implants. Macroscopically, all grit-blasted implants had delamination of the HA coating, whereas porous implants failed mostly at the HA-tissue interface. Porous-coated implants had 47% bone ingrowth and grit-blasted implants 70% (p = 0.02), however, no difference in absolute surface area was found. Part of the HA coating was resorbed during the implantation period as regards volume and thickness. HA coverage was more reduced on porous-coated than on grit-blasted implants (p = 0.01). No foreign-body reaction or osteolysis was seen. An important finding was that one fifth of the surface with complete resorption of HA coating was replaced by newly formed bone.

Animals↗
PubMed1996

Transforming growth factor-beta 1 enhances bone healing to unloaded tricalcium phosphate coated implants: an experimental study in dogs.

Growth of bone into cementless prosthetic components is compromised after revision of failed joint prostheses and by osteoporosis, gaps, and micromotion. We studied the effects of recombinant human transforming growth factor-beta 1 adsorbed on ceramic coated implants on the improvement of mechanical fixation and bone growth on the implant. Unloaded cylindrical grit-blasted titanium alloy implants were inserted bilaterally into both the medial and lateral femoral condyles of 10 skeletally mature mongrel dogs. The implants measured 10 mm in length and 6 mm in diameter and were initially surrounded by a 2 mm gap. One implant had an uncoated titanium surface and three implants were coated with tricalcium phosphate and 0, 0.3, or 3.0 micrograms of recombinant human transforming growth factor-beta 1. The dogs were killed at 6 weeks. Mechanical testing showed a 3-fold increase in fixation for the 0.3 microgram dose of recombinant human transforming growth factor-beta 1 and a 2-fold increase for the 3.0 micrograms dose. Histological analysis of bone growth on the implant demonstrated that maximal stimulation occurred with the 0.3 microgram dose, but bone volume in the gap was maximally stimulated by the 3.0 micrograms dose and increased 2-fold over control values. The majority of tricalcium phosphate was resorbed after the 6-week observation period. This study suggests that recombinant human transforming growth factor-beta 1 adsorbed onto implants coated with tricalcium phosphate ceramic can enhance mechanical fixation and bone growth on the implant. The use of transforming growth factor-beta 1 on ceramic coated prosthetic components may help to improve the functional outcome of cementless total joint replacements.

Animals↗
PubMed1996

The relationship between tumour glutathione concentration, glutathione S-transferase isoenzyme expression and response to single agent carboplatin in epithelial ovarian cancer patients.

There is evidence to suggest that glutathione (GSH) and glutathione-S-transferases (GST) are important factors in determining sensitivity to cytotoxic drugs in vitro and in preclinical in vivo model systems. To define the relationship between tumour GSH concentration, GST isoenzyme expression and response to carboplatin in epithelial ovarian cancer (EOC), tumour samples from 39 patients with assessable disease after primary surgery were analyzed for GSH content and GST expression. Response was assessed after completing six courses of single agent carboplatin therapy. GSH was measured by high performance liquid chromatography (HPLC) in fresh tumour samples taken at primary laparatomy. GST isoenzyme expression was assessed by immunohistochemistry of fixed tumour material using antibodies specific for pi, alpha and mu classes. GST isoenzyme expression was defined as positive if the staining intensity was strong and more than 10% of tumour cells were involved. The mean GSH concentrations were: 8351 +/- 4496, 7211 +/- 5026, 6559 +/- 4573 and 3758 +/- 1885 (nmol g-1 tissue dry weight mean +/- s.d.) for tumours from patients who subsequently achieved a complete response (CR, n = 18), partial response (PR, n = 10) or who had static disease (SD, n = 7) or progressive disease (PD, n = 4) respectively. There was no relationship between GSH concentration and response (ANOVA, P = 0.32). There were also no relationship between GST isoenzyme expression and response (P Fisher's exact test 0.51-0.55 and chi-squared test 0.98-0.99). In conclusion, there was no association between the concentration of GSH or expression of GST isoenzymes and response to single agent carboplatin in primary previously untreated EOC.

Antineoplastic Agents↗
PubMed1996

Transforming growth factor-beta stimulates bone ongrowth. Hydroxyapatite-coated implants studied in dogs.

Unloaded cylindrical grit-blasted titanium (Ti-6A-4V) implants (6 x 10 mm) coated with hydroxyapatite ceramic were inserted into the proximal part of the humerus of 20 skeletally mature Labrador dogs. The implants were initially surrounded by a 2 mm gap. In 10 dogs, HA-coated implants without growth factor were inserted in one humerus and implants with 0.3 microgram rhTGF-beta 1 adsorbed onto the HA coating were inserted in the contralateral humerus. In another group of 10 dogs, a dose of 3.0 micrograms rhTGF-beta 1 was tested in a similar design. All dogs were killed at 6 weeks after treatment. Results were evaluated by histomorphometry and mechanical push-out testing. Bone ongrowth was increased by one third, using the 0.3 mg rhTGF-beta 1 stimulation. Bone volume in the gap and mechanical testing showed no statistically significant differences between control and rhTGF-beta 1 stimulated implants. RhTGF-beta 1 only moderately enhanced bone ongrowth to hydroxyapatite-coated implants.

Alloys↗
PubMed1996

Growth factors: possible new clinical tools. A review.

Bone tissue contains numerous cell-to-cell signaling peptides called growth factors with potent effects on bone cell metabolism. In vivo studies over the last 5 years have demonstrated that growth factors can stimulate bone formation and bone healing and these results have made them candidates for use in orthopedic surgery. In numerous clinical conditions enhanced bone formation and bone healing could improve the results of surgery; clinical trials using growth factors to stimulate bone formation in spinal surgery, and to stimulate healing of bone defects, have been initiated. Growth factors for clinical use will become commercially available in the near future. This review describes the main growth factors and their actions in vitro and in vivo in relation to bone tissue and bone healing. Possible areas for clinical use are also discussed.

Animals↗
PubMed1996

The effect of polar projection on the perception of euclidean structure from motion.

The aim of the present study was to examine whether euclidean structure could be recovered from apparent motion sequences under polar projection. In Experiment 1, length judgments of two sides of a simulated triangle rotating in depth did not reveal effects of type of projection, polar or parallel, on the perception of euclidean structure. However, there was a significant correlation between simulated and produced slants. The results also indicated that absolute depth judgments could not be accounted for by a random mechanism suggested by Todd and Bressan (1990). Experiments 2 and 3, in which a continuous dot surface was substituted for the triangle, showed that polar projection information from a relatively large visual angle, 17.40 degrees, as compared with a small visual angle, 4.35 degrees, facilitated discrimination of depth. Produced height:width ratios were consistently related to simulated shape, although the depth dimension was underestimated. Finally, Experiment 4 showed significant correlations between simulated and produced height:width ratios that could be accounted for only by an analysis in which X and Y velocities were treated independently. As in previous experiments, the variation in the depth dimension was underestimated. It was concluded that the visual system utilizes the additional information that is available in polar projection when recovering structure from motion, but that for different reasons the perceived structure does not become euclidean. These reasons are discussed briefly.

Adult↗
PubMed1996

Perceiving motion and rigid structure from optic flow: a combined weak-perspective and polar-perspective approach.

Structure-from-motion algorithms based on weak-perspective projection have many interesting properties and could serve as a basis for a model of human perception of motion and structure from motion (M&SFM). There is some psychophysical evidence, however, that points to discrepancies between what can be accomplished with these algorithms and the performance of human subjects in certain M&SFM tasks. In light of this evidence, this paper presents a mechanism that both takes advantage of all the possibilities offered by a weak-perspective approach and behaves in a manner that is in close correspondence with human performance in M&SFM tasks. It consists of a novel weak-perspective-based method operating at small visual angles and a complementary, perspective-projection-based method operating at larger visual angles.

Algorithms↗
PubMed1996

Transforming growth factor-beta 1 stimulates bone ongrowth to weight-loaded tricalcium phosphate coated implants: an experimental study in dogs.

Bone growth into cementless prosthetic components is compromised by osteoporosis, by any gap between the implant and the bone, by micromotion, and after the revision of failed prostheses. Recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) has recently been shown to be a potent stimulator of bone healing and bone formation in various models in vivo. We have investigated the potential of rhTGF-beta 1, adsorbed on to weight-loaded tricalcium phosphate (TCP) coated implants, to enhance bone ongrowth and mechanical fixation. We inserted cylindrical grit-blasted titanium alloy implants bilaterally into the weight-bearing part of the medial femoral condyles of ten skeletally mature dogs. The implants were mounted on special devices which ensured stable weight-loading during each gait cycle. All implants were initially surrounded by a 0.75 mm gap and were coated with TCP ceramic. Each animal received two implants, one with 0.3 microgram rhTGF-beta 1 adsorbed on the ceramic surface and the other without growth factor. Histological analysis showed that bone ongrowth was significantly increased from 22 +/- 5.6% bone-implant contact in the control group to 36 +/- 2.9% in the rhTGF-beta 1 stimulated group, an increase of 59%. The volume of bone in the gap was increased by 16% in rhTGF-beta1-stimulated TCP-coated implants, but this difference was not significant. Mechanical push-out tests showed no difference in fixation of the implant between the two groups. Our study suggests that rhTGF-beta 1 adsorbed on TCP-ceramic-coated implants can enhance bone ongrowth.

Adsorption↗
PubMed1996

Etoposide phosphate infusion with therapeutic drug monitoring in combination with carboplatin dosed by area under the curve: a cancer research campaign phase I/II committee study.

The area under the plasma concentration-time curve (AUC) following an intravenous dose of etoposide varies considerably among patients, which in part contributes to the unpredictability of toxicity and response seen in individual patients. This study evaluated the utility of therapeutic drug monitoring of etoposide in reducing the interpatient variability of etoposide steady-state concentrations during prolonged infusion. The etoposide prodrug etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) was administered by infusion using an adaptive dosing strategy. It was given in combination with carboplatin, which was dosed on an AUC basis. Patients with histologically or cytologically proven small cell lung cancer were treated with etoposide phosphate by continuous 120-hour infusion and carboplatin at a dose calculated by the Calvert formula to give an AUC of 5 mg/ mL.min. Blood samples were taken on days 2 through 5 of each treatment cycle, and high-performance liquid chromatography was used to measure the plasma etoposide concentration. The resultant concentrations were compared with target concentrations of 1 or 2 micrograms/mL and these data were used to calculate the rate of infusion for the following 24 hours. In the first cohort, the target etoposide concentration was 1 microgram/mL, and this was achieved (mean +/- SD = 1.05 +/- 0.24 micrograms/mL) by infusing etoposide phosphate doses of 21 to 109 mg (15 to 68 mg/m2) per day. In the second cohort, the target concentration of 2.0 micrograms/mL was achieved (mean +/- SD = 2.05 +/- 0.31 micrograms/mL) with infused etoposide phosphate doses of 69 to 193 mg (41 to 114 mg/m2) per day. This technique reduced the variation in plasma levels and resulted in predictable hematologic toxicity. Cumulative hematologic toxicity necessitated an extension of the treatment cycle from 3 to 4 weeks, however. Of six evaluable patients, two had a complete response and one had a partial response. Therapeutic drug monitoring was shown to reduce the interpatient variation in the plasma etoposide concentration by half and shows promise for individualizing treatment with combination chemotherapy. Exploiting the known relationships between the pharmacokinetics and pharmacodynamics of these two drugs by using therapeutic drug monitoring may lead to better therapeutic safety and efficacy.

Adult↗
PubMed1995

IL-4 and IL-13, but not IL-10, are chemotactic factors for human osteoblasts.

In this study we demonstrate that the cytokines IL-4 and IL-13, but not IL-10, can induce osteoblast chemotaxis. Recombinant IL-4 (rIL-4) and rIL-13 mediated cell migration was observed using a modified multi-well Boyden chamber system. Maximum chemotaxis was observed at concentrations of 100 ng/ml of both rIL-4 and rIL-13 with a chemotactic index of 2.0 +/- 0.1 and 2.3 +/- 0.4, respectively in this system, whereas IL-10 did not show chemotactic abilities for osteoblasts. Our results suggest that IL-4 and IL-13 could take part in the recruitment of osteoblasts and thereby be of importance in the cytokine regulation of bone resorption and healing.

Cells, Cultured↗
PubMed1995

Polyethylene particles stimulate monocyte chemotactic and activating factor production in synovial mononuclear cells in vivo. An immunohistochemical study in rabbits.

We report that polyethylene particles can activate mononuclear cells within the joint to produce the monocyte chemotactic and activating factor (MCAF) and to a lesser degree interleukin 8 (IL-8) as judged by immunohistological staining. Polyethylene particles suspended in hyaluronic acid were injected weekly for 12 weeks into the right knee joint of New Zealand white rabbits. The average size of the particles was 7 (3-12) microns in diameter. The left knee joint was injected with hyaluronic acid as the control. The animals were killed after 13 weeks. On the control side, the synovial membrane was histologically normal, without signs of inflammation. In the knees that were injected with polyethylene particles, histological analysis showed a weak inflammatory response, consisting of mononuclear cells, multi-nucleated giant cells and polyethylene particles. In the vicinity of the particles, the presence of mononuclear cells that were highly positive for MCAF was noted, whereas IL-8 was present in endothelial cells and in the lining layer, but not in cells in the vicinity of polyethylene particles, suggesting that polyethylene particles are able to activate cytokine metabolism in a differentiated way in the synovial monocytes.

Animals↗
PubMed1995

The incidence of unsuspected metastases from clinically benign prostate glands with latent prostate carcinoma.

OBJECTIVE: To determine how many latent prostate gland carcinomas (unsuspected carcinomas in clinically benign prostate glands) metastasize. DESIGN: The prostate glands and the pelvic and paraaortic lymph nodes were removed at autopsy from 209 consecutive patients with clinically benign prostate glands. The prostate glands were completely sectioned and examined microscopically using full cross sections. Pelvic and para-aortic lymph nodes were identified and examined microscopically for metastases. RESULTS: Seventy-nine (38%) of the prostate glands had latent prostate carcinomas. None of the pelvic or paraaortic lymph nodes contained metastases. CONCLUSION: This study suggests that few latent prostate-gland carcinomas metastasize.

Aged↗
PubMed1995

Chemotaxis of human osteoblasts. Effects of osteotropic growth factors.

The in vitro chemotactic response of human osteoblasts was investigated towards the following growth factors: TGF-beta, PDGFs, FGFs and IGFs. Human osteoblasts grown from trabecular bone after enzymatic digestion were studied. TGF-beta stimulated the migration of human osteoblasts in a dose-dependent manner with a four-fold increase in migrated cells at 100 pg/ml, which was the optimum concentration. PDGF-BB also stimulated migration four-fold in a dose-dependent manner with a maximum response at 10 ng/ml. PDGF-AA, IGF-I and IGF-II stimulated migration two-fold at 100 ng/ml. The results show that TGF-beta and PDGF-BB are important regulators of human osteoblast migration, but other growth factors IGF-I, IGF-II and PDGF-AA may also stimulate osteoblast migration. Our results additionally suggest that TGF-beta and PDGF-BB may participate in the recruitment of osteoblasts during bone remodeling since both TGF-beta and PDGF-BB are found in bone matrix and could be released during osteoclastic bone resorption. They furthermore support a possible use of TGF-beta and PDGF-BB in growth factor-induced osteogenesis.

Cells, Cultured↗
PubMed1995

Clinical pharmacokinetic and pharmacodynamic studies with the nonclassical antifolate thymidylate synthase inhibitor 3, 4-dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)-quinazolone dihydrochloride (AG337) given by 24-hour continuous intravenous infusion.

3,4-Dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)-quinazolon e dihydrochloride (AG337) is a nonclassical inhibitor of thymidylate synthase (TS) designed to avoid potential resistance mechanisms that can limit the activity of classical antifolate antimetabolites. A clinical pharmacokinetic and pharmacodynamic study of AG337 given as a 24-h i.v. infusion was performed. Thirteen patients received 27 courses over the dose range 75-1350 mg/m2. Plasma AG337 concentrations were achieved which, in preclinical models, were associated with antitumor effects. AG337 clearance was saturable, and the pharmacokinetics of the drug at doses above 300 mg/m2 was best described by a one-compartment model with saturable elimination (median Km = 6.5 microgram/ml; range, 4.1-13 microgram/ml; median Vmax = 2.0 microgram/ml/h/m2; range, 0.96-5.6 microgram/ml/h/m2). Following the end of the infusion, AG337 was cleared rapidly (t1/2, 53-193 min), and levels were less than 0.2 microgram/ml in all patients by 48 h. Plasma protein binding was 96-98%, and the urinary excretion of AG337 as unchanged drug did not exceed 30% of the dose administered. Measurements of plasma deoxyuridine (dUrd) concentrations showed that doses of 600 mg/m2 and above of AG337 produced a consistent elevation in plasma dUrd levels (60-290%), suggesting that TS inhibition was being achieved in patients. However, in all cases dUrd concentrations had returned to pretreatment levels 24 h after the end of the infusion, suggesting that TS inhibition was not maintained. Local toxicity, probably due to the infusate pH, was the only significant adverse effect observed. These studies have shown that cytotoxic AG337 plasma concentrations can be readily achieved without acute toxicity and that these concentrations are associated with elevations in plasma dUrd levels. The lack of prolonged dUrd elevations indicates that extended administration should be explored using central line or p.o. administration to avoid local toxicity.

Antimetabolites, Antineoplastic↗
PubMed1994

Incidence, racial differences, and prognostic significance of prostate carcinomas diagnosed with obstructive symptoms.

BACKGROUND: It is unknown how often prostate carcinomas are diagnosed as a result of urinary obstructive symptoms or whether prostate carcinomas diagnosed because of obstructive symptoms have a favorable or unfavorable prognosis. It is also unknown whether racial differences in obstructive symptoms could help explain why black men with prostate carcinoma are diagnosed with more advanced stages and grades of prostate carcinoma than are white men with prostate carcinoma. METHOD: At a single Veterans Administration Medical Center, 478 consecutive cases of prostate carcinoma diagnosed between 1973 and 1985 were identified. The incidence of obstructive symptoms at diagnosis, racial differences in obstructive symptoms, and the survival of patients with and without obstructive symptoms, stratified by stage and grade, were determined. In addition, racial differences in the frequency of surgical intervention required to relieve the obstructive symptoms were determined. RESULTS: All patients diagnosed with Stage A prostate carcinoma and most (82%) patients diagnosed with Stage C prostate carcinoma had obstructive symptoms. Those diagnosed with Stage B and Stage D prostate carcinomas had with similar frequencies (53% and 55%, respectively) of obstructive symptoms. Survival, stratified by stage and grade, was similar for men with and without obstructive symptoms. The incidences of obstructive symptoms and the frequency of surgical intervention to relieve the obstructive symptoms, stage for stage, were similar for white and black men. CONCLUSION: Survival, stratified by stage and grade, is not affected adversely by obstructive symptoms. Neither racial differences in the incidence of obstructive symptoms nor the frequency with which obstructive symptoms require surgical correction explain why black men with CAP consistently are diagnosed more frequently with Stage D prostate carcinoma and less frequently with Stage A CAP than white men with CAP.

Adult↗
PubMed1994

Results of chemotherapy using ifosfamide with doxorubicin in advanced breast cancer.

Ifosfamide has single agent activity in advanced breast cancer and may potentiate the activity of doxorubicin. The combination of ifosfamide 5 g/m2 and doxorubicin 40 mg/m2 every 3 weeks for 4 cycles was used to treat 77 patients with advanced breast cancer. Fifty three patients had not received prior chemotherapy. All patients had one or more poor prognostic features, including tumor expression of epidermal growth factor receptor in 11/12 tested. The overall response rate was 74% (95% confidence intervals 62%-83%). The median survival was 9.4 months. The principal toxicities were febrile neutropenia and ifosfamide encephalopathy each in 6% of patients. A high percentage of the projected dose intensity was administered. This is a highly active combination with acceptable toxicity in advanced breast cancer, although the long term survival remains poor. Further exploration of ifosfamide in combination chemotherapy for advanced breast cancer is warranted.

Adult↗