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Biomedical subjects

M A Ritter

Publications and source records attributed to M A Ritter.

At least 55 records · Page 3Linked to original sources
PubMed1999

Intrathymic function of the human cortical epithelial cell surface antigen gp200-MR6: single-chain antibodies to evolutionarily conserved determinants disrupt mouse thymus development.

The mouse monoclonal antibody MR6 recognizes a 200 000 MW protein (gp200-MR6), which is expressed highly on human thymic cortical epithelial cells. The antigen is also expressed on some epithelial tumours and we have previously shown that MR6 inhibits the proliferation of the colon carcinoma cell lines HT29. However, the role of this molecule in the thymus is not known. In order to generate reagents that could be used in murine thymic functional studies we isolated antibodies specific to human gp200-MR6, using a phage display library expressing single-chain (sFv) antibodies. Three independent clones were isolated by panning with purified protein and their specificity was confirmed by immunohistochemistry, Western blotting and flow cytometry. In addition to human thymus, these phage antibodies also recognized the homologous antigen in mouse, pig and other species. Expressed as soluble sFv one of these clones inhibited the proliferation of HT29 cells and a mouse thymic epithelial cell line, suggesting that this antibody exhibits similar functional activity to MR6. In fetal thymic organ culture, thymocytes recovered from thymic lobes cultured in the presence of this sFv, were reduced in number fivefold compared with the control and the majority remained at the double-negative stage of development. These data indicate that gp200-MR6 plays an important role in thymocyte development. In addition, this is the first report to demonstrate that specific sFv can be used to study, and alter, thymic development. This work also highlights the advantage of phage antibody technology in selecting such reagents for functional assays.

Animals↗
PubMed1999

Determination of tumor kinetics: strategies for the delivery of radiotherapy and chemotherapy.

Both clinical and laboratory evidence indicates that local control rates for many experimental and clinical human tumors decrease with protraction of the overall duration of radiation therapy and that a likely basis for this decrease is tumor cell repopulation during treatment. Such observations have stimulated interest in tumor kinetics, and a number of techniques have been developed that increase the potential for meaningful clinical study of the proliferative behavior of tumors. This review discusses the clinical and experimental evidence for proliferation during treatment, describes two potential approaches-accelerated fractionation and concurrent chemotherapy and radiotherapy-that can be employed to counteract such intratreatment proliferation, explores methods available for measuring tumor cell kinetics, and discusses how kinetics information may be used in the future to tailor therapy to a tumor's individual characteristics.

Cell Cycle↗
PubMed1999

The clinical significance of proximal tibial resection level in total knee arthroplasty.

Clinical and radiographic data were collected in 139 patients with 195 posterior cruciate retaining total condylar knee prostheses to evaluate the relationship of the proximal tibial resection level with long term results. Among the 139 patients were 75 patients with 106 total knee replacements observed for more than 8 years. All patients underwent biyearly routine examinations, including radiographs and clinical evaluations. The average medial tibial resection for the 139 patients with 195 total knee replacements was 2.95 mm, and in the subset of 75 patients (106 knees) observed for more than 8 years, it was 3.3 mm; both groups had a maximum of 14 mm. Sixty-three percent or 67 knees had medial resection levels of 3 mm or less. The average lateral tibial resection for the 195 knees was 5.48 mm and in the 106 knees was 5.71 mm, with a maximum of 22 mm. Fifty-one percent of 104 knees had lateral resection levels of 5 mm or less. Statistical analysis showed that there was no significant correlation between the level of proximal tibial resection and Knee Society knee score, range of motion, radiolucencies, or loosening or revision. These long term results suggest that minimal proximal tibial resection is not necessary for a successful arthroplasty, and problems associated with minimal resection, such as joint line elevation and thin polyethylene inserts, can be avoided.

Adult↗
PubMed1999

Operating room environment.

Sepsis after total joint replacement is related directly to environmental contamination. Therefore, to control the source of environmental contamination, and ultimately sepsis, it must be realized that the operating room personnel are the major source of the bacteria as evidence by the rise in the colony forming units per square foot per hour from 13 units in an operating room without people to greater than 400 units during actual surgery. The use of inclusive gowns, such as hooded body exhaust, is most helpful. However, all operating room personnel including anesthesia personnel, circulating nurses, visitors, and the operating room team must wear inclusive gowns. Face masks and head covers offer no environmental protection. Some type of an environmental control, such as laminar airflow or ultraviolet light, is the most helpful with greater than 90% reduction of airborne bacteria at the wound and 60% reduction of airborne bacteria in the operating room. Therefore, to reduce environmental bacteria contamination the number of personnel in the operating room and the length of time for the actual surgery should be reduced, because wound contamination occurs first by direct fall out from the environment and second by contaminated equipment and gloved hands that initially were contaminated by the environment.

Arthroplasty, Replacement↗
PubMed1999

Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice.

Thymic atrophy is a prominent feature of malnutrition. Forty-eight hours' starvation of normal mice reduced the total thymocyte count to 13% of that observed in freely fed controls, predominantly because of a diminution in the cortical CD4(+)CD8(+) thymocyte subpopulation. Prevention of the fasting-induced fall in the level of the adipocyte-derived hormone leptin by administering exogenous recombinant leptin protected mice from these starvation-induced thymic changes. The ob/ob mouse, which is unable to produce functional leptin because of a mutation in the obese gene, has impaired cellular immunity together with a marked reduction in the size and cellularity of the thymus. We found that ob/ob mice had a high level of thymocyte apoptosis resulting in a ratio of CD4(+)CD8(+) (cortical) to CD4(-)CD8(-) (precursor) thymocytes that was 4-fold lower than that observed in wild-type mice. Peripheral administration of recombinant leptin to ob/ob mice reduced thymocyte apoptosis and substantially increased both thymic cellularity and the CD4(+)CD8(+)/CD4(-)CD8(-) ratio. In contrast, a comparable weight loss in pair-fed PBS-treated ob/ob mice had no impact on thymocyte number. In vitro, leptin protected thymocytes from dexamethasone-induced apoptosis. These data indicate that reduced circulating leptin concentrations are pivotal in the pathogenesis of starvation-induced lymphoid atrophy.

Animals↗
PubMed1999

Intra-articular morphine and/or bupivacaine after total knee replacement.

The postoperative analgesic effects of intra-articular injections of bupivacaine and/or morphine were examined prospectively in 437 patients who had total knee replacement for osteoarthritis. They were divided randomly into four groups. Group I received 10 mg of morphine (1 ml) and 9 ml of saline, group II received 10 ml of bupivacaine (2.5 mg/ml), group III received 10 ml of saline, and group IV received 10 mg of morphine (1 ml) and 9 ml of bupivacaine (2.5 mg/ml). All analgesics administered in the first 24 hours after operation were recorded. The patients rated their pain on the McGill-Melzack scale at 1, 6, 12 and 24 hours. No significant differences were found between any of the groups in the use of Demoral and/or Toradol in 24 hours, the length of stay in hospital or the pain rating at 1, 6, 12 or 24 hours. Patients in groups I and IV, whose injections included morphine, used significantly more morphine in the first 24 postoperative hours than did groups II or III.

Adult↗
PubMed1999

Radiological factors influencing femoral and acetabular failure in cemented Charnley total hip arthroplasties.

We have made a retrospective review of 185 cemented Charnley total hip arthroplasties performed between 1970 and 1974 to determine the relationships between radiological variables and failure of the femoral and acetabular components. We measured the acetabular wear, the orientation of the cup, the thickness and consistency of acetabular and femoral cement mantles, radiolucency and femoral alignment. The mean follow-up was for 11.7 years. Femoral loosening was demonstrable radiologically in 15 hips (8.1%), ten (5.4%) of which were revised during the period of follow-up. Only when the first postoperative radiograph showed a thin cement mantle in Gruen zone 5 was there a significant association with failure of the femoral component. There were 12 loose acetabular components (6.5%), nine (4.8%) of which were revised. When the initial radiograph after operation showed radiolucency in DeLee and Charnley zone 1, the incidence of acetabular loosening was 28.21%. If such radiolucency was not present, the incidence of acetabular loosening was only 0.69%. Our findings emphasise the importance of careful cementing.

Acetabulum↗
PubMed1999

Patellar complications (total knee arthroplasty). Effect of lateral release and thickness.

One thousand, one hundred forty-six Anatomic Graduated Component total knee arthroplasties performed between 1987 and 1989 were used to investigate the effects of patellar thickness alone or coupled with lateral retinacular release on initial patellar complications and maximal flexion. Lateral release was found not to be statistically significant regarding radiolucency, patellar prosthesis loosening, or an increase or decrease in flexion. However, total knee arthroplasties in which a lateral release was done, which either saved the superior lateral genicular artery or sacrificed the superior lateral genicular artery, were found to increase the incidence of initial patellar fractures and/or loosening (complications within 1 year) when compared with total knee arthroplasties in which a lateral release was not performed. There was no statistical difference in failure rates regarding fractures and/or loosening of the patella between lateral releases in which the superior lateral genicular artery was saved and the lateral releases in which the superior lateral genicular artery was sacrificed. A difference in postoperative patellar thickness compared with preoperative patellar thickness was found not to be significant to initial patellar fracture and/or loosening, patellar fracture alone, patellar loosening alone, radiolucency, the need for a lateral release, or to an increase or decrease in flexion. Lateral release and patellar thickness had no significant effect on patellar fracture and/or loosening.

Adult↗
PubMed1998

A solid water pelvic and prostate phantom for imaging, volume rendering, treatment planning, and dosimetry for an RTOG multi-institutional, 3-D dose escalation study. Radiation Therapy Oncology Group.

PURPOSE: With increased interest in 3-D conformal radiation therapy and dose escalation, it is necessary to provide advanced techniques to assure quality in treatment delivery. Multi-institutional trials for these newer treatment techniques require methods of verifying the consistency of treatments between the participating institutions. For this reason, a phantom was designed to address the quality and consistency of Radiation Therapy Oncology Group (RTOG) 3-D prostate treatment protocol. METHODS AND MATERIALS: A solid water pelvic and prostate phantom for imaging, volume rendering, treatment planning, and dosimetry applications for performing comprehensive quality assurance has been designed and fabricated. Its configuration was based upon CT slices obtained from a patient study. Individual slices were machined with corresponding contours of the prostate, bladder, rectum, and the left and right femurs. Most of the phantom is made of solid water (Gammex/RMI, Middleton, WI), while the femurs are made of bone-equivalent material. The CT numbers from patient images were used to adjust the solid water composition within the organ volumes, providing image contrast from the remainder of the phantom. Cylindrical insertion grooves are machined in the phantom to allow placement of ionization chambers and thermal luminal dosimeters (TLDs) for dosimetry applications. During imaging, the cavities are filled with rods fabricated from solid water material. RESULTS: The phantom is being used to evaluate the consistency of a range of processes in radiation therapy simulation, planning, and delivery of 3-D-based treatments for prostate cancer. CONCLUSION: The ultimate study objective is to use the phantom to evaluate the accuracy and consistency of treatments delivered by institutions participating in national collaborative clinical trials involving 3-D conformal dose escalation.

Humans↗
PubMed1998

Association between interleukin-4-producing T lymphocyte frequencies and reduced risk of graft-versus-host disease.

BACKGROUND: We have previously developed and used limiting dilution analysis to measure frequencies of alloreactive cytotoxic T cell precursors (CTLp) and interleukin (IL)-2-producing T helper cells (IL-2/HTLp) to assess the risk of graft-versus-host disease in bone marrow transplantation (BMT). However, no test has been available to measure precursor frequencies of the important IL-4-secreting subset. METHODS: We have now established a limiting dilution analysis to measure the frequency of IL-4-producing T helper cells (IL-4/HTLp) using the IL-4-responsive indicator cell line CT.h4S and have applied this assay to measure alloreactive IL-4/HTLp frequencies in BMT donor-recipient pairs. These frequencies were then analyzed in the context of clinical data to assess the relationship between the number of donor anti-recipient IL-4-secreting T cells and disease outcome. RESULTS: Frequencies of IL-4/HTLp have been studied in HLA-identical siblings, HLA-"matched" unrelated, and HLA-mismatched combinations and found to range from approximately 1/500,000 in HLA-identical sibling pairs to -1/2,000 in HLA-DR-mismatched pairs. These frequencies were independent of those for IL-2/HTLp and showed a negative correlation with those for CTLp. Clinical follow-up of 30 patients showed that high IL-4/HTLp frequencies are associated with a reduced risk of severe graft-versus-host disease. High IL-4/HTLp frequencies may also indicate an increased risk of leukemia relapse. CONCLUSIONS: Our data suggest that measurement of IL-4/HTLp frequencies provides information distinct from that obtained with CTLp and IL-2/HTLp. This new assay provides a valuable additional method for optimizing donor selection in unrelated BMT.

Animals↗
PubMed1998

The gp200-MR6 molecule which is functionally associated with the IL-4 receptor modulates B cell phenotype and is a novel member of the human macrophage mannose receptor family.

The human gp200-MR6 molecule has previously been shown to have either an antagonistic or agonistic effect on IL-4 function, demonstrated by inhibition of IL-4-induced proliferation of T cells or mimicking of IL-4-induced maturation of epithelium, respectively. We now show that gp200-MR6 ligation can also mimic IL-4 and have an anti-proliferative pro-maturational influence within the immune system, causing up-regulation of co-stimulatory molecules on B lymphocytes. Biochemical analysis and cDNA cloning reveal that gp200-MR6 belongs to the human macrophage mannose receptor family of multidomain molecules. It comprises 1722 amino acids in toto (mature protein, 1695 amino acids; signal sequence, 27 amino acids) organized into 12 external domains (an N-terminal cysteine-rich domain, a fibronectin type II domain and 10 C-type carbohydrate recognition domains), a transmembrane region and a small cytoplasmic C terminus (31 amino acids) containing a single tyrosine residue (Y1679), but no obvious kinase domain. Strong amino acid sequence identity (77%) suggests that gp200-MR6 is the human homologue of the murine DEC-205, indicating that this molecule has much wider functional activity than its classical endocytic role. We also show that the gp200-MR6 molecule is closely associated with tyrosine kinase activity; the link between gp200-MR6 and the IL-4 receptor may therefore be via intracellular signaling pathways, with multifunctionality residing in its extracellular multidomain structure.

Amino Acid Sequence↗
PubMed1998

Pharmacokinetics of intravenous and oral losartan in patients with heart failure.

The pharmacokinetics of a selective AT1-subtype, nonpeptide, orally active, angiotensin II receptor antagonist, losartan, were characterized in 11 patients with heart failure (New York Heart Association class II, n = 6; class III, n = 4; class IV, n = 1) after oral and intravenous administration. In these patients, average plasma clearance of losartan was 566 mL/min, volume of distribution at steady-state was 34 L, and terminal plasma half-life was 1.5 hours. Average bioavailability was 36%. No clinically significant accumulation of losartan or its active metabolite, EXP3174, occurred after multiple-dose oral administration for 7 to 8 days. Terminal plasma half-life of EXP3174 after oral administration of losartan was 7.6 hours. The pharmacokinetics of losartan in patients in this study appear to be similar to those in healthy subjects studied previously.

Administration, Oral↗
PubMed1998

Interferon-alpha therapy in HCV hepatitis: HLA phenotype and cirrhosis are independent predictors of clinical outcome.

Interferon-alpha therapy is effective in only approximately 20% of individuals with chronic HCV infection. A knowledge of the genetic and/or environmental factors that underlie this heterogeneity of response should provide useful predictors of clinical outcome. HCV infected patients and healthy subjects were selected from the expatriate Egyptian population living in Qatar, where chronic HCV infection poses a serious health problem. HCV infection was confirmed by ELISA and RT-PCR. Fifty five patients received interferon-alpha therapy for 6 months and their response was assessed by liver enzyme activity and histology of liver biopsies; the patient responses were followed during treatment and for 1 year afterwards. Twenty five patients were characterised as responders, and the remaining 30 as non-responders. All individuals in the study were typed for HLA class II alleles. Data were analysed by univariate and multivariate statistical methods. Expression of the HLA DR2 Major Histocompatibility class II allele is significantly associated with a beneficial response to interferon-alpha therapy in Egyptian patients (p < 0.005). This association is independent of cirrhosis, the absence of which also showed a significant association with response to therapy (p < 0.005). Our results therefore provide evidence that HLA DR2 is an important additional factor for predicting a long term response to interferon-alpha therapy in chronic HCV hepatitis.

Adult↗
PubMed1998

Life expectancy after total hip arthroplasty.

A total of 3,807 patients undergoing total hip arthroplasty (THA) between the years 1970 to 1995 were evaluated for mortality. Patient age groups were designated in 10-year intervals as follows: age <40; 41-50; 51-60; 61-70; 71-80; age >80. The life expectancy estimate of the patients with THA was calculated by the Kaplan-Meier method, and that of the normal population was obtained from standard life-tables. Statistical significance was evaluated using 95% confidence limits. A significant difference in life expectancy was found in patient age groups >60 (61-70, 71-80, >80) demonstrating significantly higher survival rates among THA patients when compared with the normal population.

Adult↗
PubMed1998

Predictors of transfusion risk in elective knee surgery.

Two hundred seventy-nine patients undergoing primary unilateral total knee replacement and 280 patients undergoing primary bilateral total knee replacements were reviewed retrospectively. Patients' height, weight, hemoglobin level before donation, hemoglobin level before surgery, autologous donation, number and type of transfusions whether autologous or allogeneic, and hemoglobin at discharge were collected from hospital and clinic records. The average drop in hemoglobin was 3.85 g/dL in the group of patients undergoing unilateral total knee replacement and 5.42 g/dL in the group of patients undergoing bilateral total knee replacements. The preoperative hemoglobin and blood volume seemed to be very strong, statistically significant predictors of transfusion risk in single and bilateral knee replacements. In unilateral total knee replacement, patients with a hemoglobin of greater than 13 g/dL had only an 8% chance of transfusion and if they donated autologous blood, 66% of the blood was wasted. Preoperative anemia was a strong predictor of transfusion risk in patients undergoing unilateral and bilateral total knee replacements and carried a very high allogeneic transfusion exposure risk, even in patients who had donated blood preoperatively. A nomogram was developed using blood volume and predonation hemoglobin to predict transfusion risk and need to predeposit autologous blood in patients undergoing unilateral and bilateral total knee replacements.

Aged↗