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Biomedical subjects

M A Ritter

Publications and source records attributed to M A Ritter.

At least 19 recordsLinked to original sources
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↗
PubMed1992

A novel adhesion molecule in the murine thymic microenvironment: functional and biochemical analysis.

The rat monoclonal antibody (mAb) 4F1, raised against mouse thymic stromal cells, recognizes cortical epithelium in tissue sections of mouse thymus; however, in flow cytometry, activated leucocytes (T cells, B cells, and macrophages) and transformed thymocytes are also positive for the 4F1-antigen (4F1-Ag). Western blotting, under both reducing and nonreducing conditions, demonstrates that the molecule to which 4F1 binds is expressed in four forms, 29, 32, 40, and 43 kD, all of which carry N-linked carbohydrate; and that the structure is identical on epithelium and lymphocytes. The 4F1-Ag on cortical epithelium is partially sensitive to PI-PLC treatment, whereas on transformed epithelial and lymphoid cell lines, it was resistant to this enzyme. The molecule, therefore, may exist in both transmembrane and phosphoinositol-linked forms. In functional blocking experiments, mAb 4F1 gave inhibition of both T-cell proliferation in MLR and of cytotoxic T-cell killing of alloantigenic targets; it also blocked adhesion of transformed thymocytes to thymic epithelial cells in vitro. These molecular and functional characteristics suggest that the 4F1-Ag is a novel adhesion molecule that may be involved both in intrathymic T lymphocyte differentiation and in peripheral T-cell function.

Animals↗
PubMed1992

Prostate-specific antigen as a predictor of radiotherapy response and patterns of failure in localized prostate cancer.

PURPOSE: A study of preradiation and postradiation, serial serum prostate-specific antigen (PSA) levels was performed in patients who had clinically localized prostate cancer. The prognostic value of the PSA in pretreatment evaluation and posttreatment follow-up was assessed. PATIENTS AND METHODS: Sixty-three patients who presented with clinically localized prostate cancer and who were treated with external-beam radiation therapy were followed-up for a median of 25 months. A serum PSA and physical examination were performed at 3-month intervals, and a bone scan was done yearly. An increase in PSA triggered an additional metastatic workup. Prostate rebiopsy was performed for new, palpable nodules or for a serial increase in PSA in the context of a negative metastatic workup. RESULTS: Forty-one patients remained recurrence-free and 22 recurred clinically, 15 distantly and seven locally. The PSA was the strongest, independent, pretreatment prognostic indicator (P = .019) among pretreatment PSA, stage, and grade, but lost significance when the serum prostatic acid phosphatase (PAP) status was included. The initial rate of the PSA decrease after radiation (median half-life, 2.6 months) failed to predict outcome. Recurrence-free patients reached postradiation PSA levels that were equivalent to those reported in disease-free male populations; failure of the PSA to reach such normal levels was a multivariate predictor of subsequent failure (P less than .037). All clinicopathologic documentations of failure were preceded by an increase in PSA levels during follow-up. Delayed versus early PSA increase was associated with clinically localized versus metastatic first recurrence. CONCLUSIONS: The serum PSA is an independent pretreatment and posttreatment predictor of outcome. Additionally, for a median follow-up of 25 months, delayed PSA failure is associated with clinically localized rather than metastatic recurrence, a relationship that may help in selection for local salvage therapy.

Aged↗
PubMed1992

Short-term treatment with nonsteroidal antiinflammatory medications to prevent heterotopic bone formation after total hip arthroplasty. A preliminary report.

The effect of short-term postoperative treatment with nonsteroidal antiinflammatory medication to prevent the formation of heterotopic ossification (HO) after total hip arthroplasty (THA) was studied in two groups of patients. Group A included 46 noncemented THAs in 40 men. Eight patients (13 hips) received prophylaxis with 25 mg of indomethacin three times daily for 14 days, and 32 patients (33 hips) received prophylaxis of 650 mg of aspirin twice daily for six weeks. Six to 12 months after surgery, only one hip (aspirin treated) developed HO, this being Grade I. In group B, 17 hips in 17 patients with cemented THA received prophylaxis of 25 mg of indomethacin three times daily. Of these, 12 patients were given indomethacin from one to nine days. One year after surgery, five hips had no HO and seven hips showed a Grade I or Grade II lesion. The remaining five patients in Group B received indomethacin from 19 to 26 days; one developed HO. This study demonstrated that treatment with either 650 mg of aspirin twice daily for six weeks or 25 mg of indomethacin three times daily for the first 14 postoperative days is sufficient to prevent the formation of severe HO after THA.

Adult↗
PubMed1991

Interleukin 4 receptor expression on human lung tumors and normal lung.

Interleukin 4 (IL-4) receptors were detected by a monoclonal antibody on tumor cells of 10 of 29 squamous cell carcinomas and 6 of 17 adenocarcinomas of the lung. None of the small cell carcinomas or carcinoid tumors stained. Parallel sections stained for epidermal growth factor receptors showed that all but 2 of the IL-4 receptor-positive tumors also expressed epidermal growth factor receptors. Positive labeling for IL-4 receptors was also obtained on nonneoplastic bronchial epithelium and on lymphocytes and macrophages infiltrating the tumor stroma. The role of IL-4 and its receptor in normal human lung is unknown, but the expression of IL-4 receptors on particular subtypes of lung tumors suggests that they may have a role in differentiation or proliferation of squamous and adenocarcinomas.

Adenocarcinoma↗
PubMed1991

The thymus in seronegative myasthenia gravis patients.

In 5-10% of all patients with typical generalised myasthenia gravis (MG), serum antibody to the acetylcholine receptor (AChR) is undetectable. To determine whether these represent a distinct subgroup, we have compared the thymuses of 14 seronegatives, 70 seropositives and 12 non-myasthenic controls. By quantitative immunohistology on coded sections, the 7 seronegative samples were clearly distinguishable from the controls by the pronounced lymph node-type T-cell areas in the medulla. While these closely resembled those in the seropositive cases, germinal centres were significantly sparser, and total in vitro IgG production was disproportionately low (per B cell) in the 12 cases tested. Furthermore, specific anti-AChR production was never detected in any of these cultures. The data support the view that the medullary T-cell areas are the most consistent abnormality in the MG thymus (though it may not be primary), and they strongly imply that seronegative and seropositive MG are distinct entities.

Adolescent↗
PubMed1991

Revision total knee arthroplasty. A survival analysis.

The results of revision total knee arthroplasty (TKA) have been documented reasonably well in the literature. It is notable, however, that none of these reports have used the technique known as survival analysis to compare virgin and revision arthroplasties. This technique has an advantage over conventional analyses because it does not exclude patient data for inadequate follow-up study or patient death. In this study, survival analysis was applied to 37 revision TKAs performed exclusively by the senior author. With failure defined as removal of the prosthesis, revision surgeries experienced a 97.0% survival rate at 6 years. The secondary arthroplasty demonstrated a significantly lower survival rate than the index procedure over a period of approximately 6 years.

Actuarial Analysis↗
PubMed1991

Xenogeneic monoclonal antibodies in the management of cancer: control of their in vivo immunogenicity and induction of specific unresponsiveness using an antibody-drug immunoconjugate.

A bispecific mouse monoclonal antibody (mAb) that recognises carcinoembryonic antigen (CEA) with one binding site and vinblastine (VLB) with the other was used, and its in vivo immunosuppressive effect specific for anti-mouse immunoglobulin (Ig) was studied. The antibody was incubated with VLB at a molar ratio (MR) of 1:1, and administered i.v. to rabbits. Control animals received either the MAb alone, or the MAb with VLB covalently linked (MR 1:1), or the parental anti-CEA with equimolar amount of VLB. Seven days later, the rabbit anti-mouse Ig primary response was measured, and found to be almost 55% reduced in the animals that received the VLB 'loaded' MAb. In vivo kinetics and stability experiments revealed that the T1/2 of the MAb was 68 +/- 5 h, whereas free VLB disappeared within minutes. It was concluded that as soon as the drug dissociates from the antibody's binding site, it is rapidly removed. This problem was overcome by subcutaneously implanting osmotic mini-pumps containing VLB. The pumps released the drug at a constant rate for a period greater than 1 week, saturating the antibody's binding site. Under these conditions rabbits developed 80% less anti-mouse Ig antibodies when the bispecific antibody was administered (compared with the parental anti-CEA). The immunosuppression observed was specific for the mouse Ig, under conditions compatible with the full clinical therapeutic potential of the MAb. In conclusion, these experiments show, that it is possible to develop hybrid antibodies that can act as a 'lethal bait' to any specific lymphocyte in vivo, thus preventing undesirable responses against the xenogeneic MAb.

Animals↗
PubMed1991

The effects of blockade of interleukin 2 receptors and interleukin 4 receptors on cytokine production.

The understanding of the regulation of cytokine production and T-cell proliferation by other cytokines is far from complete. We have examined the supernatant concentration of different cytokines in cultured peripheral blood lymphocytes (PBL) incubated with monoclonal antibodies against the interleukin-2 receptor (IL-2R) or interleukin-4 receptor (IL-4R) complex in order to analyse the importance of these receptors in the production of other cytokines. The PBL cultures were stimulated with phytohaemagglutinin and phorbol myristate acetate. The addition of anti-Tac to PBL cultures resulted in increased free IL-2 due to blockade of IL-2R. MR6 (a monoclonal antibody against IL-4R) did not affect the supernatant concentration of IL-2 in cultured PBL. Blockade of IL-2R or IL-4R both resulted in increased IL-4 in supernatant. The increase in supernatant concentration of IL-4 in PBL cultured with MR6 was due to a direct interaction with the IL-4R complex but the increase in IL-4 with anti-Tac was due to the accumulation of free IL-4 as an effective blockade of IL-2R prevented the full expression of IL-4R. Neither anti-Tac nor MR6 affected the IL-6 production by activated PBL, suggesting the existence of an IL-2- and IL-4-independent pathway. Blockade of IL-2R or IL-4R both resulted in a reduction of interferon-gamma (IFN-gamma) production, indicating that both endogenously generated IL-2 and IL-4 are important mediators of IFN-gamma induction in PBL cultures stimulated with T-cell mitogens.

Antibodies, Monoclonal↗
PubMed1991

Unwashed filtered shed blood collected after knee and hip arthroplasties. A source of autologous red blood cells.

We evaluated the results of twelve hematological and plasma protein determinations in 450 to 500-milliliter volumes of shed blood that had been collected with or without acid-citrate-dextrose anticoagulant (National Institutes of Health Formula A) from knees and hips during the first twelve hours after arthroplasty. We also evaluated the effects on the recipients when the blood was used for reinfusion. The findings in the units that had been obtained in less than four hours, in between four and six hours, and in more than six hours after the arthroplasty were similar whether or not the acid-citrate-dextrose anticoagulant had been used. The mean values for the collected units were: in the blood, a concentration of hemoglobin of 115 grams per liter, a hematocrit of 0.34, a white blood-cell count of 4.8 x 10(9) per liter, and a red blood-cell count of 3.7 x 10(12) per liter, and, in the plasma, a level of hemoglobin of 160 grams per liter, a level of fibrinogen of less than 0.2 gram per liter, a level of factor-V clotting protein of less than 10 per cent of normal, a level of factor-VIII clotting protein that was 45 per cent of normal, a level of antithrombin III that was 45 per cent of normal, a level of plasminogen that was 55 per cent of normal, a level of protein C that was 100 per cent of normal, and a level of fibrin-degradation products of 1000 micrograms per milliliter of plasma. The clinical response of the patient was assessed after the reinfusion of a total of 205 units of unwashed shed blood into 153 patients. In addition, in 126 of the 153 patients, hematological and plasma-protein measurements were analyzed before the autotransfusion and one and twenty-four hours afterward. Each of these patients had received one to four units of shed blood that had been filtered but not washed. Only two (2 per cent) of the ninety-nine patients who received shed blood that had been collected six hours or less after the operation had a febrile reaction, whereas twelve (22 per cent) of the fifty-four patients who received blood that had been collected six to twelve hours after the operation had such a reaction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Survivorship of cementless total knee arthroplasty without tibial plateau screw fixation.

Seventy-two cementless tricompartmental total knee arthroplasties were performed in 47 patients using a porous-coated prosthesis without screw fixation for the tibial components between 1984 and 1986. These individuals were observed at regular intervals for a minimum of three years. Their Hospital for Special Surgery pain and function scores as well as roentgenographic signs of anatomic alignment and subsidence were evaluated at six months, one year, and three years postoperatively. The roentgenographic evaluation for subsidence looked at a measurable difference in the anteroposterior roentgenograph on the medial and lateral plateaus and on the lateral roentgenograph anteriorly and posteriorly. Early postoperative interpretations have suggested pain and knee scores to be much lower than scores in the cemented prosthesis. Reassessment after three years, however, revealed no further deterioration of the noncemented prosthesis in respect to knee scores and survival analysis. Roentgenographic analysis showed no correlation between subsidence and alignment alterations, subsidence and time, or subsidence and pain. It appears that after an initial period of discomfort, the noncemented knee can achieve a functional, clinical, and roentgenographic result much better than previously anticipated. The consequences beyond this time period still remain unknown.

Aged↗
PubMed1990

Determination of the molecular nature and cellular localization of Thy-1 in human renal tissue.

The molecular nature and cellular localization of Thy-1 antigen in human renal tissue were studied. Strong immunohistochemical staining was observed in frozen sections of human kidney using monoclonal anti-human Thy-1 antibody; this reaction was almost completely abolished by pretreating the kidney section with phosphatidyl inositol (PI)-specific phospholipase C (PI-PLC). Immunohistochemical analysis revealed that the Thy-1 antigen is localized on the proximal tubular epithelial cells and the Bowman's capsule of the glomerulus. Northern blot analysis of renal mRNA using a cloned human Thy-1 gene revealed the presence of human Thy-1 mRNA of a similar size to the one in human brain. When a human kidney cDNA library was screened with the same probe, a cDNA of human Thy-1 was isolated. Moreover, human Thy-1 protein with a molecular weight (MW) of 21,000 was detected in renal tissue by gel electrophoresis and Western blot analysis using monoclonal anti-human Thy-1 antibody. These data demonstrate for the first time the production of human Thy-1 as a PI-anchored protein with a unique cellular location in human renal tissue.

Adult↗
PubMed1979

B-cell precursors in early chicken embryos.

The ontogeny of B-cell precursors in chicken embryos from day 3 of incubation onwards has been studied. Purified antibodies to chicken Ig L, gamma, mu, alpha chains were used in a sensitive indirect immunofluorescence assayed on fixed cell smears and wax-embedded tissue sections; the location and morphology of immunoglobulin positive (Ig+) cells were determined either in phase contrast or after histological staining. Lymphoid cells containing small amounts of cytoplasmic immunoglobulin were found in 3 day and older embryonic yolk sac, 11 and 12 day blood, 11, 12 and 13 day bursal mesenchyme. cIg+ large basophilic cells were first seen in 14 day bursal follicles. It is concluded that cells enter the embryonic bursa at different developmental stages: some appear to be uncommitted stem cells, whilst others have already commenced B-cell maturation in an extra-bursal site.

Animals↗