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Biomedical subjects

M A Ritter

Publications and source records attributed to M A Ritter.

At least 163 records · Page 9Linked to original sources
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

Keynote address: integration of cytostatic agents and radiation therapy: a different approach to "proliferating" human tumors.

Failure to achieve local and regional tumor control with radiation therapy remains a significant problem for a number of anatomic sites and can have a negative impact upon survival. There is emerging clinical and laboratory evidence that proliferation of tumor clonogens during the course of radiation treatment significantly impairs local control. Recent in situ studies suggest that as many as half of all human carcinomas have the potential to double their cell number in 5 or fewer days. Thus, cells that survive the initial treatments might rapidly repopulate a tumor, resulting in local failure. One potential clinical approach to reduce the impact of tumor cell repopulation during treatment would be to administer biological or chemical modifiers to slow or inhibit tumor proliferation. Examples of these cytostatic modifiers which are available for clinical testing now, or in the near future, include hormones, anti-hormones, growth factors, growth factor antagonists and other biologicals (e.g., interferons). Clinical alteration of the proliferative status of tumors could influence tumor control by reducing the impact of tumor cell proliferation during therapy, by modifying tumor cell radiosensitivity, or by favourably altering both. To appreciate the magnitude and the cumulative effect of these factors, newer technologies and experimental model systems need to be exploited in investigating correlations between proliferation and tumor control and between proliferative status and radiosensitivity. The design of future clinical trials using cytostatic agents and radiotherapy will rely heavily upon such basic information.

Antineoplastic Agents↗
PubMed1991

The total condylar III knee prosthesis in elderly patients.

Sixteen knee arthroplasties using a total condylar III prosthesis were performed in 14 patients with an average follow-up period of 4.5 years and a minimum follow-up period of 3 years. Eleven of the sixteen knee arthroplasties were revision prostheses. The average age was 71 year, with all but three patients being 69 years of age or older. In this age group, fifteen of sixteen implants had a good to excellent Hospital for Special Surgery (HSS) knee score at the most recent follow-up evaluation. One patient had a fair score, the result of a remote postoperative proximal tibial fracture, and requires a long leg brace for ambulation.

Aged↗
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

Trochanteric fixation by cable grip in hip replacement.

We used the stainless steel cable grip system described by Dall and Miles in 1983 to fix trochanters in 40 hips after total arthroplasty with trochanteric osteotomy. The cable broke in 32.5% of the hips; the trochanter failed to unite in 37.5%. Significantly more cables broke when placed inside the femoral canal than when the cable was placed round the femoral shaft (58% as against 9.5%, difference p less than 0.01). The high incidence of breakage may have resulted from contact between the stainless steel cable and the titanium prosthesis, from the acute angulation, or because of the lower fatigue strength of stainless steel. Better results have been obtained using cables with a higher fatigue strength, passed outside the proximal femur.

Adult↗
PubMed1991

Early clinical results of hydroxyapatite-coated total hip arthroplasty.

A retrospective clinical and radiographic review of 25 conventional cementless total hip replacements (THRs) and 25 cementless hydroxyapatite-coated THRs was performed to evaluate early postoperative results. The hydroxyapatite-coated group had a higher incidence of pain-free arthroplasties compared with the standard cementless group (72% v 44%, P = .045) at the 2-month postoperative evaluation. At the 6-month evaluation, 76% of hydroxyapatite-coated THRs were pain-free compared with 52% of conventional cementless THRs, although the statistical significance disappears (P greater than .05). No differences between groups existed in the 6-month Harris hip scores, average motion, use of external support, Trendelenberg gait, postoperative implant radiolucent lines. Adding a 50- to 75-mug hydroxyapatite coating to a proximal one-third porous femoral prosthesis and porous surface acetabular cup improved the early clinical results in cementless THR. Whether this improvement in pain scores reflects a more stable cementless prosthesis via increased rates and amount of osseus ingrowth or adjunctive bone hydroxyapatite chemical bonding remains unanswered. Long-term follow-up of femoral subsidence and THR revision is needed to indicate the durability and success of hydroxyapatite coating.

Adult↗
PubMed1991

Survival analysis of total condylar-type prostheses.

Between 1975 and 1983, 280 patients received 422 posterior cruciate ligament-retaining total condylar knee arthroplasties. Fifty-nine were excluded for one of the following reasons: previous total knee replacement, follow-up less than 1 year, or infection at any time during the life of the prosthesis. The 363 remaining knees were observed from 1 to 13 years (mean, 6.86). Kaplan-Meier and "crude" survival estimates at 12 years were 94.7% and 96.6%, respectively. Results of various survival analyses by other authors yield similar successful results.

Follow-Up Studies↗
PubMed1991

The effect of miscellaneous invasive procedures on subsequent total knee arthroplasty.

Invasive orthopedic procedures were performed on 112 joints that underwent total condylar knee arthroplasty between November 1975 and February 1987. These knees were divided into six categories based on the most traumatic surgical procedure the patients had experienced. The six classifications were total knee arthroplasty, proximal tibial osteotomy, fracture fixation, patellectomy, arthroscopy, and debridement. Each group of knees was compared with the 579 primary arthroplasties performed during the same time period. The only group in which results were significantly less favorable than those of the virgin joints was the previous total arthroplasty category. All other surgical classification groups had knee scores, radiolucency frequencies, and ranges of motion comparable with those of the primary replacement surgeries. When surgical techniques are modified to insure proper soft tissue alignment, patients who have undergone previous invasive procedures on their knees can expect highly favorable results from total joint arthroplasty.

Arthroscopy↗
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↗