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Biomedical subjects

W N Scott

Publications and source records attributed to W N Scott.

At least 37 records · Page 2Linked to original sources

The efficacy of arthroscopy following total knee replacement.

We evaluated the utility and safety of arthroscopy for diagnosing and treating symptoms in problematic total knee replacements. From 1988 to 1995, 40 arthroscopies were performed on 38 patients with an average age of 68.4 years. The average onset of symptoms post knee replacement was 33.7 months (range 1 month to 15 years), and the average duration of symptoms prior to arthroscopy was 15.6 months (range 1 month to 5 years). Presenting symptoms included pain in 73%, catching or soft tissue impingement in 35%, and stiffness in 20% of patients. Our protocol involves 24 hours of perioperative, intravenous antibiotics, and two or three routine arthroscopic portals. There were no arthroscopy-related complications or infections. Arthroscopy successfully diagnosed the etiology of the patient's symptoms in all but one case (97.5%). Operative diagnoses included impinging soft tissue under the patella consistent with the "clunk" syndrome (43%), impinging hypertrophic synovitis elsewhere in the knee (15%), impinging PCL stump (10%), prosthesis loosening or wear (10%), and arthrofibrosis (20%). Arthroscopic treatment consisted of removal of impinging tissue or loose body as indicated. Additionally, eight of the patients had a manipulation under anesthesia with an average improvement in flexion of 26.3 degrees postoperatively. At an average follow-up of 19.9 months, 27.5% of knees had developed recurrent symptoms. Two of these patients had repeat arthroscopy for recurrent impinging hypertrophic synovitis. The rates of successfully relieving symptoms without recurrence according to operative diagnosis were 82% for "clunks," 60% for other impinging synovium or soft tissue, and 63% for arthrofibrosis. Three patients underwent total knee revisions. Knees were rated at follow-up using the Knee Society rating system with patients divided according to functional category. The average Knee Society knee scores and function scores respectively were 93 and 92 for group A patients, 91 and 88 for group B patients, and 81 and 76 for group C patients. Arthroscopy successfully identified all cases of soft tissue impingement and prosthetic loosening or wear, and successfully treated 73% of patients without recurrence. There were no arthroscopy associated complications or infections. Thus, arthroscopy is a safe, effective tool for managing certain problematic knee replacements, especially "clunks," and may help to avoid revision or arthrotomy in some cases.

Aged↗

Difficulties with the "N + 7 rule" in endoscopic anterior cruciate ligament reconstruction.

In an effort to facilitate the use of interference screw fixation in the tibia, a method to orient the tibial tunnel termed the "N + 7 Rule" was prospectively applied to 60 consecutive endoscopic anterior cruciate ligament reconstructions performed by a single surgeon. Four cases were excluded because a breach in the described protocol for application of the N + 7 rule was identified at the time of the operation. Of the remaining 56 cases, 28 (50%) were fixed with an interference screw on the tibia, whereas 28 (50%) required fixation with sutures tied over a post. The 28 cases not amenable to interference screw fixation included 17 cases in which the tibial tunel was too long and 11 cases in which the tunnel was too short. It appears that the applicability of the N + 7 rule to an individual surgeon's practice may be altered by small variations in operative technique.

Adult↗

Transforming growth factor-beta isoform expression in human ovarian tumours.

The expression patterns of members of the transforming growth factor-beta (TGF-beta) family were analysed in 96 primary ovarian tumours by RNAse protection assay. mRNA for the three mammalian isoforms, TGF-beta 1, TGF-beta 2 and TGF-beta 3, was detected in 46, 66 and 66% of 74 malignant tumours, respectively, with the predominant patterns of expression being either dual or triple co-expression. TGF-beta II receptor expression, detected by reverse-transcription PCR, was present in 92% malignant tumours. Expression patterns were similar between malignant, borderline and benign tumours, although TGF-beta 1 incidence was reduced in benign tumours. In malignant tumours, the incidence of TGF-beta 1 expression was less than that of either TGF-beta 2 (P = 0.02) or TGF-beta 3 (P = 0.0014), while in both malignant and borderline tumours, TGF-beta 2 and TGF-beta 3 tended to be co-expressed. Aneuploid tumours were more likely than diploid tumours to express multiple rather than single forms of TGF-beta (P = 0.018). The incidence of TGF-beta 1 expression was reduced in PR-moderate/rich (PR > 20 fmol/mg protein) relative to PR-negative/poor tumours (P = 0.048), while TGF-beta 3 expression was increased in ER-moderate/rich (ER > 20 fmol/mg protein) tumours compared to ER-negative/poor tumours (P = 0.0012). Expression of TGF-beta 3, but not TGF-beta 1 or TGF-beta 2, was associated with advanced stage disease (P = 0.014) and, in the malignant group, reduced survival (P = 0.02) with a hazard ratio of 2.6. These data suggest a possible role for TGF-beta 3 in the progression of ovarian cancer.

Disease Progression↗

Total knee replacement in young, active patients. Long-term follow-up and functional outcome.

We reviewed our experience with total knee arthroplasties performed between 1977 and 1992 in patients who were fifty-five years old or less to determine the appropriate management for younger patients who have severe osteoarthrosis. One hundred and fourteen knee replacements were performed in eighty-eight patients who were an average of fifty-one years old (range, twenty-two to fifty-five years old). All of the operations were performed by one of the two senior ones of us (J. N. I. or W. N. S.) with the use of cementing techniques. A posterior stabilized, posterior cruciate-substituting design was used for all but one replacement, for which a semiconstrained total condylar prosthesis was used. Six knees (four patients) were lost to follow-up. Follow-up data for the remaining 108 knees (eighty-four patients) were used to perform the survivorship analysis. One hundred and three unrevised knees (eighty patients) were available for clinical evaluation with the scoring systems of The Hospital for Special Surgery and the Knee Society at an average of eight years (range, three to eighteen years) postoperatively; thirty-six knees were followed for more than ten years. In addition, the activity levels of the patients were assessed with the activity score of Tegner and Lysholm. Radiographs were examined for evidence of loosening of the component. At the latest follow-up examination, the average knee score according to the system of The Hospital for Special Surgery had improved from 55 points preoperatively to 92 points. According to the system of the Knee Society, the average knee score was 94 points and the average functional score was 89 points. The result for all 103 knees was good or excellent according to the knee scores of The Hospital for Special Surgery and the Knee Society. Ninety-seven knees (94 per cent) had good or excellent function according to the functional score of the Knee Society. The average activity score of Tegner and, Lysholm improved from 1.3 points (range, 0 to 4 points) preoperatively to 3.5 points (range, 1 to 6 points) at the latest follow-up examination. All but two patients had improvement in the activity score postoperatively, and nineteen (24 per cent) of the eighty patients had an activity score of at least 5 points, indicating regular participation in activities such as tennis, skiing, bicycling, or strenuous farm or construction work. Nine (9 per cent) of the 103 knees had non-progressive tibial radiolucent lines. Two patients had a revision because of late infection, and one patient had revision of a well fixed tibial component because of wear of the polyethylene. In addition, three patellar components were revised for loosening, and one spacer was exchanged to treat instability. With failure defined as revision of either the femoral or the tibial component, the over-all rate of survival was 94 per cent at eighteen years. When the three patellar revisions were included in the failures, the survival rate was 90 per cent at eighteen years. When the exchange of the spacer was also included in the failures, the survival rate was 87 per cent at eighteen years. We consider arthroplasty with cementing of a posterior stabilized total knee prosthesis to be effective operative treatment with durable results for osteoarthrosis in younger patients when other, less invasive measures have failed. Within the average eight-year follow-up interval of this study, polyethylene wear, osteolysis, and loosening of the conforming posterior cruciate-substituting prosthesis were not major problems for these younger, active patients, although it is possible that this observation could change with an even longer duration of follow-up.

Adult↗

Murine epidermal growth factor peptide (33-42) binds to a YIGSR-specific laminin receptor on both tumor and endothelial cells.

A laminin-antagonist peptide, comprising amino acids 33-42 of murine epidermal growth factor (mEGF-(33-42)), interacts with a breast cancer- and endothelial cell-associated receptor, which is specific for the laminin B1 chain sequence, CDPGYIGSR-NH2 (Lam.B1-(925-933)), and is immunologically similar to a previously described 67-kDa laminin receptor. In whole cell receptor assays, mEGF-(33-42), Lam. B1-(925-933), and laminin all have IC50 values for displacement of 125I-laminin in the range 1-5 nM. Cell attachment to solid-phase laminin is also blocked by all three ligands, but in contrast to the receptor assays, mEGF-(33-42) or Lam.B1-(925-933), while equipotent with each other, were less effective than laminin. The concentrations of the peptides required to produce half-maximal inhibition of attachment were in the range 230-390 nM, but those for laminin were 1000-fold lower, in the range 0.2-0.3 nM. Like laminin, solid-phase mEGF-(33-42) supports cell attachment, and this ability is blocked by anti-67-kDa receptor antibodies. Modeling studies suggest that both peptides present a tyrosyl and an arginyl residue on the same face of a right-handed helical fold with elliptical cross-section.

Amino Acid Sequence↗

Histologic comparison of posterior cruciate ligaments from arthritic and age-matched knee specimens.

Twenty-four posterior cruciate ligaments (PCLs) harvested at the time of total knee arthroplasty (TKA) were histologically compared with an age-matched group of 36 PCLs harvested from above-knee amputations, cadavers, and bone bank donors. Ligaments were considered histologically abnormal and degenerative if either loose, mucoid, myxoid, or cystic changes were noted. The magnitude of degeneration was defined as normal, slight, mild, moderate, or marked, based on the amount of tissue demonstrating change. Examination of the PCLs from the TKA group demonstrated 17% normal ligaments, 20% with mild focal changes, and 63% with marked degenerative changes. The control group demonstrated 45% normal cruciate ligaments and 33% with slight, 11% with mild, and 11% with moderate focal changes. No PCL from the control group showed marked changes. The overall degenerative changes between these two groups were found to be statistically significant (P < .001). This study demonstrated that the PCL obtained at the time of TKA is characterized by distinct histologic degenerative changes that are different from age-related changes (P < .001) and that the PCL is not spared degenerative changes in involved osteoarthritic knees. This may help explain the finding that the PCL in osteoarthritic knees is biomechanically abnormal. Many studies have reported excellent results with TKA systems that retain the PCL, implying that a completely normal PCL is not required or that neural input is sufficient for proper kinematic knee function in knees that have undergone total joint arthroplasty.

Aged↗

Soft tissue expansion prior to arthroplasty in the multiply-operated knee. A new method of preventing catastrophic skin problems.

Ten knees in nine patients underwent gradual soft tissue expansion prior to major knee surgery. All patients had multiple prior operative procedures around the knee. The resultant multiple skin incisions were felt to potentially jeopardize the postoperative status of the soft tissues. Each knee underwent the surgical placement of a tissue expander through a bed of adjacent healthy soft tissue followed by the gradual inflation of the expander over an average of 64.5 days. The average volume of soft tissue expansion was 313.7 mL per knee. Subsequent major knee surgery requiring an arthrotomy was performed at the time of expander removal followed by uncomplicated soft tissue closure. All wounds healed without any complications.

Adult↗

The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer.

The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor alpha (TGF-alpha) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-alpha mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-alpha mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-alpha mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-alpha (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-alpha (P = 1.00). EGF receptor mRNA expression was significantly and positively associated with serous histology (P = 0.006) but not with stage or grade. Neither EGF nor TGF-alpha showed any link with histological subtype or stage. The survival of patients with malignant tumours possessing EGF receptor mRNA was significantly reduced compared with that of patients whose tumours were negative (P = 0.030 for all malignant tumours; P = 0.007 for malignant epithelial tumours only). In contrast, neither the expression of TGF-alpha nor EGF was related to survival. These data suggest that the presence of EGF receptor mRNA is associated with poor prognosis in primary ovarian cancer.

Base Sequence↗

Murine epidermal growth factor (EGF) fragment (33-42) inhibits both EGF- and laminin-dependent endothelial cell motility and angiogenesis.

Laminin, murine epidermal growth factor (mEGF), and the synthetic laminin peptide Lam.B1(925-933) (a linear peptide from the B1 chain of murine laminin, CDPGY1GSR-amide) all stimulate endothelial cell motility above basal rates, whereas a synthetic mEGF fragment, mEGF33-42 (a linear peptide from the C-loop of mEGF, acetyl-C-[S-Acm]-VIGYSGDR-C-[S-Acm]-amide), inhibits motility. In both human SK HEP-1 and embryonic chick endothelial cells, mEGF33-42 blocks both EGF- and laminin-stimulated locomotion of endothelial cells. In vivo, mEGF33-42 also blocks both laminin- and mEGF-induced angiogenesis in the chick. In the human cell line. Lam.B1(925-933) has an additive effect in coincubation with either laminin or mEGF, but it blocks their effects in the chick cells. Lam.B1(925-933) alone stimulates angiogenesis in the chick but blocks laminin-induced angiogenesis. Thus, mEGF33-42 acts as a general laminin antagonist, whereas Lam.B1(925-933) acts as a laminin agonist in human cells, but in chick cells it acts as a partial antagonist. We propose that the presence of an anionic group at the eighth residue of mEGF33-42 may be the source of the antagonistic effects seen with this peptide as compared with the laminin fragment. These findings have important implications in the design of human antiangiogenic agents, and also in the use of chick models in the study of human disease.

Amino Acid Sequence↗

Electrical stimulation effect on extensor lag and length of hospital stay after total knee arthroplasty.

The effects of electrical stimulation in conjunction with traditional physical therapy, on knee extensor lag and length of hospital stay among patients recovering from total knee arthroplasty were assessed. Forty patients who underwent total knee replacement (TKR) were randomly assigned to either an electrical stimulation group (16 females, 5 males), or a control group (15 females, 4 males). Both groups received conventional physical therapy including continuous passive motion (CPM) to the affected limb, ambulation training, range of motion exercises, and activities of daily living (ADL) training. The experimental group additionally received electrical stimulation during CPM treatment. Experimental group subjects reduced their extensor lag from 7.5 to 5.7 degrees, whereas control group extensor lag increased from 5.3 to 8.3 degrees. These trends were significantly different (p < .01). Rehabilitation discharge criteria were reached in 6.7 days in the experimental group and 7.4 days in the control group. These differences were also significant (p < .05). The results of this study indicate that the application of electrical stimulation during recovery from TKR can effectively reduce extensor lag and decrease the length of hospital stay.

Activities of Daily Living↗

Atrial natriuretic factor enhances the hydroosmotic response of toad bladder to submaximal doses of vasopressin.

Using the toad urinary bladder, we examined the effects of submaximal levels of atrial natriuretic factor (ANF) upon the hydroosmotic water flux caused by physiologic concentrations of vasopressin (VP). Pretreatment with ANF prior to the addition of VP (10(-9)M) significantly enhanced water transport (123 +/- 23%) compared to tissues exposed to VP alone. Pre-treatment with ANF also significantly enhanced the hydroosmotic response (143 +/- 43%) to cyclic-3',5'-adenosine monophosphate (cyclic-AMP). When the concentration of VP was progressively increased during time course experiments, an inhibitory effect of ANF on water transport followed the early stimulatory response to this peptide. The data support a novel, dose-dependent modulatory role for ANF early in the response of transporting epithelia to VP. Moreover, the stimulatory effect of submaximal doses of ANF to cyclic-AMP mediated water transport suggest the possibility that modulation by ANF may occur at a site following the VP receptor-linked adenylate cyclase system.

Animals↗

Transforming growth factor-beta mRNA expression and growth control of human ovarian carcinoma cells.

The pattern of TGF beta expression and in vitro response to TGF beta has been defined in three ovarian carcinoma cell lines (PEO1, PEO4 and PEO14). Marked differences in both mRNA expression and growth responses were detected between the cell lines. All expressed mRNA for TGF beta 3, PEO1 and PEO4 but not PEO14 expressed mRNA for TGF beta 1, whereas PEO14 but not PEO1 and PEO4 expressed TGF beta 2. Growth of PEO14 cells in culture was markedly inhibited by both TGF beta 1 and beta 2. PEO1 cells were inhibited by TGF beta 1, but not TGF beta 2 whilst growth of PEO4 cells were not affected by exposure to either of these peptides. These data indicate that several elements of potential autocrine loops involving TGF beta's are present within ovarian cancer cells.

Cell Cycle↗

Growth control by epidermal growth factor and transforming growth factor-alpha in human lung squamous carcinoma cells.

Although EGF receptor expression is generally elevated in human lung squamous carcinoma, the biological significance of this phenomenon and the role of EGF and TGF-alpha in this disease are poorly understood. We have investigated three human lung squamous carcinoma cell lines (NX002, CX140 and CX143) and have shown, using an antibody (EGFR1) directed against the EGF receptor, that the majority of cells in all three lines express the EGF receptor. Using a ligand binding assay, Scatchard analysis indicated high concentrations (1,300-2,700 fmol mg-1 protein) of a single low affinity binding site (Kd = 3-5 nM) within these lines. Addition of EGF or TGF-alpha at concentrations greater than 0.1 nM resulted in growth inhibition of all three lines and this was associated with an accumulation of cells in the G2/M phase of the cell cycle. Growth inhibitory effects were not explained by an enhancement of cellular differentiation as monitored by involucrin expression and the ability to form cornified envelopes. While the presence of EGF could not be detected in medium conditioned by the NX002 cell line, mRNA for TGF-alpha was detected in all three lines suggesting the possibility of an autocrine loop. These results together with reports of growth inhibition by EGF and TGF-alpha in other systems suggest that EGF and similar molecules might have a growth regulatory role in lung cancer cells and modulation of such may have therapeutic potential.

Carcinoma, Squamous Cell↗

Arthroscopic evaluation and treatment of the patellofemoral joint.

Patellofemoral pain is a multifactorial problem. No single successful solution for problems related to the patellofemoral joint has been identified. One needs to consider the interaction of all of the factors affecting the extensor mechanism. Evaluation begins with a careful history, physical examination, and appropriate radiographic studies. Arthroscopy can provide additional information regarding the condition of the articular cartilage, patellar tracking, and the presence of other intra-articular lesions. Conservative treatment is the cornerstone of management and is effective in more than two-thirds of patients, making surgical treatment necessary in only a minority of instances. ALRR, although not an innocuous procedure, has an acceptably low complication rate and provides predictably good results when used in properly selected patients.

Arthroscopy↗

Using biological measurements, can patients with benign breast disease who are at high risk for breast cancer be identified?

In order to address the question of whether biological measurements might identify women with benign breast disease (BBD) at particular risk for breast cancer, analyses were performed on cyst fluids aspirated from patients presenting with palpable breast cysts. Electrolyte profiles showed that cyst fluids may be divided into major subpopulations which differ in terms of histological appearance of cyst lining epithelium, pattern of cyst presentation, and levels of other fluid constituents such as androgen conjugates and epidermal growth factor. Analysis of cyst fluids from 18 patients who subsequently developed breast cancer 1 to 8 years later showed that 12 individuals had group A cysts, three had group B cysts, and three presented with a mixture of the two types. Therefore, although this represents an increased proportion of group A cysts as compared with the total population of cyst fluids studied over the same time period, individuals subsequently developing breast cancer were not confined to one subgroup of cysts. Androgen conjugate and growth factor content also did not predict for subsequent cancer. At the present time, it is therefore concluded that biochemical measurements in cyst fluids cannot accurately identify women likely to develop breast cancer. However, the routine aspiration of cysts does provide the opportunity to monitor the local microenvironment of the breast.

Androgens↗

Mutagens in human breast cyst fluid.

Cyst fluids aspirated from patients presenting with palpable cysts of the breast were analysed for mutagenic activity, as determined by the Ames test. Of the 439 women studied, 9.6% had mutagen-positive fluids. There was no obvious relationship between the presence of mutagen-positive fluids and clinical or epidemiological details of the women from which they were obtained. Preliminary characterisation of the mutagenic activity suggested that the responsible agents have diverse chemical properties.

Adult↗

Factors influencing the response of MCF-7 cells to an agonist of luteinising hormone-releasing hormone.

To clarify the mechanism by which the luteinising hormone-releasing hormone agonist, buserelin, may have direct effects on breast cancer cells, factors potentially influencing its action have been studied in the MCF-7 breast cancer cell line. Oestradiol and epidermal growth factor (EGF), which stimulate the growth of MCF-7 cells in culture, reversed, at least in part, the inhibitory effects of buserelin. Insulin also abolished growth inhibition. Quantitative effects of buserelin differed according to the batch of fetal calf serum used as media supplement. These data suggest that the direct inhibitory effects of buserelin on breast cancer cells are mediated at least in part by an antagonism of growth-promoting factors.

Breast Neoplasms↗