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Biomedical subjects

M A Ritter

Publications and source records attributed to M A Ritter.

At least 145 records · Page 8Linked to original sources
PubMed1994

Studies on the thymus of non-obese diabetic (NOD) mice: effect of transgene expression.

The non-obese diabetic (NOD) mouse is a good model of insulin-dependent diabetes mellitus. Autoreactive T cells may play a fundamental role in disease initiation in this model, while disregulation of such cells may result from an abnormal thymic microenvironment. Diabetes is prevented in NOD mice by direct introduction of an E alpha d transgene (NOD-E) or a modified I-A beta chain of NOD origin (NOD-PRO or NOD-ASP). To investigate if disease pathology in NOD mice, protection from disease in transgenic NOD-E and NOD-PRO and partial protection from disease in NOD-ASP can be attributed to alterations in the thymic microenvironment, immunohistochemical and flow cytometric analysis of the thymi of these mouse strains was studied. Thymi from NOD and NOD-E mice showed a progressive increase in thymic B-cell percentage from 12 weeks of age. This was accompanied by a concomitant loss in thymic epithelial cells with the appearance of large epithelial-free areas mainly at the corticomedullary junction, which increased in size and number with age and contained the B-cell clusters. Such thymic B cells did not express CD5 and were absent in CBA, NOD-ASP and NOD-PRO mice as were the epithelial cell-free spaces, even at 5 months of age. Therefore the mechanisms of disease protection in the transgenic NOD-E and NOD-ASP/NOD-PRO mice may differ if these thymic abnormalities are related to disease.

Animals↗
PubMed1994

Long-term survival analysis of a posterior cruciate-retaining total condylar total knee arthroplasty.

From 1975 to 1983, 278 patients received 418 posterior cruciate ligament-retaining Total Condylar knee arthroplasties. Twenty-four patients were excluded, 15 for lack of followup data, 6 for infection during followup, and 3 for revision surgeries for previous infections. The 394 remaining knees were observed from 1 to 18 years (mean, 8.08 years). Kaplan-Meier and crude survival estimates at 12 years were 96.8% and 98.1%, respectively. Various survival analyses by other authors have yielded similar successful results.

Adult↗
PubMed1994

Polyethylene wear in uncemented acetabular components.

We measured polyethylene wear in 231 porous-coated uncemented acetabular cups. We divided the hips into two groups according to the fixation of the femoral component, by cementing (n = 97) or press-fit (n = 134). Follow-up was from three to five years. The patients in two sub-groups were matched for weight, diagnosis, sex, age and length of follow-up. The linear wear rate of cups articulated with uncemented femoral components (0.22 mm/year) was significantly higher than the wear rate (0.15 mm/year) of cups articulated within cemented femoral components (p < 0.05). These results can be compared with previously reported wear rates of 0.08 mm/year for cemented all-polyethylene cups and 0.11 mm/year for cemented metal-backed cups. The higher wear rates of uncemented arthroplasties could jeopardize the long-term results of this type of hip replacement.

Acetabulum↗
PubMed1994

Postoperative alignment of total knee replacement. Its effect on survival.

Four hundred twenty-one posterior cruciate condylar total knee arthroplasties were performed between 1975 and 1983. Anatomic alignment of the knee was recorded on follow-up evaluations from two months to 13 years postoperatively. Patients were stratified into a normal group that was 5 degrees to 8 degrees anatomic valgus, a varus group that was from 4 degrees anatomic valgus to any degree of varus, and a valgus group that was more than 9 degrees anatomic valgus. There were eight failures, five in the varus group and three in the normal group. There were no failures in the valgus group. Kaplan-Meier survival curves showed no significant difference between normal and valgus groups; however, there was a statistical difference between the valgus and varus and the normal and varus groups. A surgeon should align a total knee prosthesis in neutral or a slight amount of anatomic valgus to give the patient the best chance for long-term survival.

Aged↗
PubMed1994

In vitro radiation-induced neoplastic progression of low-grade uroepithelial tumors.

Recent interest has focused on the identification of molecular genetic mechanisms in multistep neoplastic transformation. In vitro exposure of simian virus 40 (SV40)-immortalized human uroepithelial cells (SV-HUC) that are environmentally relevant to bladder carcinogens has been shown to produce tumorigenic transformation, as assessed by the ability of cells exposed to a carcinogen to form xenograph tumors with heterogeneous cancer phenotypes ranging from very aggressive, invasive high-grade carcinomas to superficial low-grade indolent tumors. In addition, exposure of a low-grade indolent tumor generated in the SV-HUC system, MC-T11, to the same carcinogens results in neoplastic progression as assessed by the production of high-grade aggressive cancers. In the present study, we show neoplastic progression of MC-T11 after in vitro exposure to a single dose of 6 Gy X rays. In addition, we show that the chromosome deletions, including losses of 4q, 11p, 13q and 18, observed in these radiation-induced tumors are similar to those observed in carcinogen-induced tumors, thus supporting the hypothesis that the experimental cell system, not the transforming agent, dictates the genetic losses required for tumorigenic transformation and progression.

Animals↗
PubMed1993

Modulation of proliferation kinetics in human squamous cell carcinomas of the head and neck.

OBJECTIVE: Proliferation of tumor clonogens during a course of conventional head and neck radiotherapy serves to compromise ultimate tumor control. Biologic strategies that attempt to alter tumor proliferation kinetics using cytostatic or antiproliferative agents may therefore prove valuable by limiting tumor cell repopulation during therapy. DESIGN: Three human squamous cell carcinoma (SCC) cell lines, derived from primary head and neck cancers, have been characterized in vitro via flow cytometric analysis of proliferation kinetics, and in vivo via tumor xenograft growth evaluation in athymic mice. RESULTS: The antiproliferative agent alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, induced growth inhibition of these SCCs in culture and when administered orally to athymic mice harboring SCC tumor xenografts. Cell cycle kinetic analysis via flow cytometry revealed that DFMO induced a lengthening of in vitro tumor cell potential doubling times. Similarly, DFMO administered continuously via the drinking water to athymic mice harboring human SCC xenografts induced a prolongation of in vivo tumor volume doubling. CONCLUSIONS: These data indicate that biologic agents, such as DFMO, can alter SCC growth kinetics and may prove useful in designing new therapeutic strategies for rapidly proliferating tumors such as those that occur in the head and neck.

Animals↗
PubMed1993

Development in the thymus: it takes two to tango.

Intrathymic T-cell development is dependent upon signals provided by the thymic stromal cell microenvironment. However, loss of thymic T cells in natural and experimentally induced situations is associated with a reduction in the surrounding epithelium, suggesting an interdependence between thymocytes and their microenvironment. Here, the authors review the evidence in favour of this intrathymic symbiosis, and hypothesize that T cells may provide maturation and survival signals that are necessary for the development and maintenance of their microenvironment.

Animals↗
PubMed1993

Polyethylene wear in total hip arthroplasty in patient-matched groups. A comparison of stainless steel, cobalt chrome, and titanium-bearing surfaces.

Osteolysis and component loosening secondary to polyethylene (PE) debris are of paramount concern to today's joint replacement surgeon. This retrospective clinical study measures linear wear in 568 implanted total hip prostheses in which three different metals were used as bearing surfaces (307 stainless steel T-28 [Zimmer, Warsaw, IN], 162 cobalt chrome Tr-28 [Zimmer], and 99 nonion implanted titanium Miami Orthopedic Surgical Consultants [Biomet, Warsaw, IN] prostheses) implanted by a single surgeon over an 8-year period. The acetabular component in all cases was nonmetal-backed compression-molded PE, and all components were cemented. Linear wear was measured using the radiographic technique described by Livermore et al. (The effect of femoral head size on wear of the polyethylene acetabular component. J Bone Joint Surg 72A:518, 1990) in which change in acetabular component thickness is determined from serial radiographs. A separate evaluation of this technique confirmed accuracy to within 0.18 mm. Radiographs were also evaluated for femoral and acetabular radiolucencies, femoral subsidence, and osteolysis. Patients were matched for sex, age, weight, and length of follow-up period to eliminate these retrospective variables for comparison of wear. The patient-matched groups consisted of 77 patients from each group (43 women, 34 men) with the following demographics: age, 66 years; weight, 158.9 lbs.; follow-up period, 7.9 years. Results revealed linear wear rates of 0.06 stainless steel, 0.05 cobalt chrome, and 0.08 titanium in the patient-matched groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Evidence that rapamycin has differential effects of IL-4 function. Multiple IL-4 signaling pathways and implications for in vivo use.

The immunosuppressive drug rapamycin, which inhibits the response of T cells to growth-promoting lymphokines, has been considered to act as a general inhibitor of cytokine action. Our investigations into the effect of rapamycin on human IL-4, a cytokine controlling B and T cell function, show this not to be the case. Unexpectedly, rapamycin actually synergized with IL-4 in both the upregulation of CD23 expression and the down-regulation of the type II (p75) TNF receptor, while in the same B cell line, rapamycin simultaneously inhibited the IL-4-dependent production of TNF alpha and beta. These results raise the possibility that multiple IL-4 signaling pathways may be responsible for the pleiotropic effects of IL-4, and have important implications for both the experimental and possible clinical in vivo use of rapamycin as a selective immunosuppressant.

B-Lymphocytes↗
PubMed1993

Expression of the alpha beta T-cell receptor is necessary for the generation of the thymic medulla.

The architecture of the thymus of mice that congenitally fail to express the alpha beta T-cell receptor (TCR alpha beta) has been examined by immunohistology. In these mice, a defined mutation was introduced into the TCR alpha gene by homologous recombination. By using antibodies specific for cortical or medullary epithelium and for major histocompatibility complex antigens, the network of cortical epithelium in these mice was shown to be essentially unaltered in comparison with that of normal mice. In contrast, the thymic medulla was considerably reduced in size. This analysis shows that expression of the alpha beta TCR but not the gamma delta TCR is obligatory for establishing the thymic medulla and suggests that the growth of medullary epithelial cells may require contact with TCR alpha beta-expressing cells.

Animals↗
PubMed1993

Polyethylene wear in cemented metal-backed acetabular cups.

We examined radiographic polyethylene wear in 233 cemented total hip arthroplasties (201 patients) with either a metal-backed or a non-metal-backed acetabular cup. All patients had identical cemented one-piece titanium femoral stems with a femoral head diameter of 28 mm. The mean linear wear rate was 0.11 mm/yr in metal-backed sockets and 0.08 mm/yr in non-metal-backed sockets (p = 0.0002). The mean volumetric wear rate was 66.2 mm3/yr in the metal-backed sockets and 48.2 mm3/yr in the polyethylene sockets (p = 0.0002). The addition of metal backing to a cemented acetabular cup therefore resulted in a 37% increase in mean polyethylene wear rates which may partially explain the higher failure rate of cemented metal-backed cups. Linear regression analysis also implicated increased follow-up time (log), gross acetabular migration, metal backing and male gender in increasing polyethylene wear. We advocate the use of an all-polyethylene cup in cemented total hip arthroplasty. The increased polyethylene wear must also cause concern about the wear rate of uncemented metal-backed acetabular sockets.

Acetabulum↗
PubMed1993

Use of lateral heel and sole wedges in the treatment of medial osteoarthritis of the knee.

The authors discuss the use of lateral heel wedges in the treatment of medial osteoarthritis of the knee in 121 knees in 85 patients. Follow-up was an average of 12 months after the insertion of the wedge. Patients' roentgenograms were graded according to the Ahlback classification, and various improvements were noted. Overall, 38% of patients improved to a Hospital for Special Surgery pain score of 25 or 30, which corresponds to an excellent result from total knee arthroplasty. Fifty percent of patients improved to a pain score of 20 or higher, which corresponds to a good result from total knee arthroplasty. The patients with milder osteoarthritis received greater pain relief. However, even patients with complete loss of joint space and bony erosion showed some improvement. It appears that the use of lateral wedges has a place in the conservative treatment of medial osteoarthritis.

Adult↗
PubMed1993

Intramedullary versus extramedullary femoral alignment systems in total knee replacement.

The accuracy of intramedullary (IM) versus extramedullary (EM) distal femoral alignment systems was compared in 200 consecutive total knee replacements (TKRs) on standing full-length lower-extremity roentgenographs. Intramedullary femoral alignment systems were used in 125 TKRs and an EM system was used in 75 TKRs. All tibial cuts were made using an EM tibial cutting guide. Roentgenographic measurements of (1) femoral-tibial angle, (2) distal-femoral resection angle, (3) proximal-tibial resection angle, (4) joint line orientation, (5) physiologic femoral valgus, and (6) distance of the lower-extremity mechanical axis from the center of the knee were made. No significant intragroup differences were seen in the average values obtained for each of the six roentgenographic measurements. However, the percentage of distal-femoral resections outside the accepted normal range (94 degrees-100 degrees) was higher in the EM group (28%) versus the IM group (14.4%) at p = 0.019. Likewise, the percentage of joint line orientations outside the desired normal range was higher in the EM groups when compared with the IM group (21.3% versus 11.2%, p = 0.052). A disturbing number of proximal-tibial resection angles were inaccurate in both groups. Improper tibial cuts were seen in 20.6% of Group 1 and in 24% of Group 2 when an EM tibial cutting guide was used. A range of distal-femoral cuts exists when using either an IM or an EM femoral alignment guide. This study demonstrated a statistically significant improvement in distal-femoral resection accuracy when using an IM femoral alignment system. Methods of improving proximal-tibial bone resections are needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Biometry↗
PubMed1992

Single biopsy, tumor kinetic analyses: a comparison of methods and an extension to shorter sampling intervals.

There is emerging and established clinical and laboratory evidence that proliferation of tumor clonogens during radiation therapy can impair local tumor control. The pre-treatment, tumor potential doubling time, T(pot), estimated with in situ bromodeoxyuridine (BrdUrd) labeling, followed by a single biopsy and flow cytometry, may be a predictor of a given tumor's ability to undergo such intra-treatment proliferation. Recent studies have found a strong similarity between T(pot)'s determined in this fashion and the effective doubling times of surviving tumor cells during radiotherapy, as estimated from tumor control versus treatment duration data. Furthermore, several preliminary clinical studies have indicated that T(pot) may be a predictor of outcome, with faster tumors doing worse. Accelerated fractionation might overcome such proliferation, but is more acutely toxic and is unlikely to benefit patients with slowly proliferating tumors. Thus, the BrdUrd/single biopsy method may offer the possibility of selecting between accelerated and conventional or hyperfractionated treatment. Several approaches to the analysis of data generated by this method have been described, but there has been little documentation of the validity of methods in experimental systems, particularly in human experimental tumors. This study explores various analytic methods employed with the BrdUrd, delayed, single-biopsy technique used in determining the potential doubling time, T(pot), of tumors. It compares methods of analysis in three experimental systems and in 40 in situ-labeled human tumors, and proposes a method for shortening the required labeling-biopsy interval to a clinically more convenient range of 3 to 4 hours.

Animals↗
PubMed1992

The effect of preoperative knee deformity on the initial results of cruciate-retaining total knee arthroplasty.

Between November 1985 and June 1987, 751 posterior cruciate-sparing total knee arthroplasties were performed on 523 patients who exhibited fixed varus or valgus deformities. Patients excluded from this study included the following: those with a postoperative follow-up period of less than 2 years (including patients who had died), patients who became infected, and patients with previous failed total knee arthroplasty in the same knee. A total of 473 knees left for evaluation. All arthroplasties were measured using anatomic axis for alignment measurement. The Hospital for Special Surgery scoring system was used to determine the clinical scores prior to the end of each follow-up examination. All ligament releases were performed sequentially, including balancing of the posterior cruciate ligament. All arthroplasties were divided into six separate groups depending upon the degree of varus or valgus deformity. Kaplan-Meier curves were constructed using three methods of failure definition. Curves were then compared between groups. The mean Hospital for Special Surgery score was no different between any of the groups, except for the group of 6 degrees-10 degrees varus, which was significantly higher than the mean score of the 11 degrees and higher valgus group. All other groups were the same statistically. It is concluded that severe varus and valgus deformities may be satisfactorily corrected with the use of a cruciate-retaining type of total knee arthroplasty.

Adult↗
PubMed1992

Influential factors in cemented acetabular cup loosening.

To delineate further the cause of acetabular loosening in a group of 238 total hip arthroplasties performed between 1980 and 1982, the authors subjected those total hip arthroplasties to a multifactorial analysis utilizing the log normal model. Data collected on each patient consisted of age, sex, weight at the time of surgery, diagnosis, cement thickness between zones 1 and 2 and between zones 2 and 3, polyethylene thickness, lateral tilt, and metal backing of the acetabular components. The acetabulum was considered a failure by radiographic loosening with migration greater than 5 mm, revision in patients younger than 60 years of age (P = 0.154), or when the acetabular cup was metal-backed (P = .001).

Aged↗