Biomedical subjects

S V Medendorp

Publications and source records attributed to S V Medendorp.

At least 37 records · Page 2Linked to original sources

PubMed1993

Therapeutic effects of a synthetic peptide of C-reactive protein in pre-clinical tumor models.

Previous studies have shown that multilamellar vesicles (MLV) or other carriers containing purified human C-reactive protein (CRP) have therapeutic activity in preclinical tumor models. Here we evaluated the therapeutic effects of MLV containing novel synthetic peptides, derived from the structure of CRP, on the extent of (a) established lung metastases of fibrosarcoma T241 in C57Bl/6 mice, (b) survival of C57Bl/6 mice bearing established liver metastases of colon carcinoma MCA-38, and (c) primary tumor growth of Renca renal carcinoma in Balb/c mice. In all cases, a single synthetic CRP peptide, RS-83277, demonstrated significant antitumor effects comparable to that seen with intact CRP. Two other synthetic CRP peptides, RS-83287 and RS-83147, showed no therapeutic activity and were comparable to control MLV containing only buffer. None of the peptides contained sequences homologous with that of the phagocyte stimulant, tuftsin. Activity of MLV-encapsulated RS-83277 was dose-dependent, and a comparable dose of the soluble peptide, given either alone or following injection of buffer-MLV, was ineffective. These results demonstrate immunotherapeutic potential for a novel synthetic peptide derived from CRP, and endogenous acute-phase protein.

Adenocarcinoma↗

PubMed1993

Prognostic significance of flow cytometry in non-small-cell lung cancer.

To clarify the value of deoxyribonucleic acid (DNA) ploidy analysis, we prospectively studied single-parameter flow cytometric findings of fresh tissue from 272 patients with primary non-small-cell lung cancer from whom adequate tissue from the lung cancer was available. The mean age of the patients was 65.5 years; 65.8% were men. Histologic types were as follows: adenocarcinoma, 107 (39.3%); squamous cell, 100 (36.8%); large cell, 56 (20.6%); adenosquamous, 8 (2.9%); and giant cell, 1 (0.4%). Histologic grades were as follows: I (well differentiated), 15 (5.5%); II, 100 (36.8%); and III, 157 (57.7%). American Joint Committee on Cancer stages were as follows: I, 151 (55.5%); II, 38 (14%); III, 74 (27.2%); and IV, 9 (3.3%). Survivals at 1 year and 3 years were 74.2% +/- 2.8% and 52.4% +/- 4.8%, respectively. For non-squamous cell lung cancer, multivariate analyses with the Cox proportional hazards regression model for survival showed (1) that increasing American Joint Committee on Cancer stage (p < 0.001), male gender (p = 0.02), and histologic grades II and III (p = 0.04) were of independent (negative) prognostic significance and (2) that the presence and absence of DNA aneuploidy (p = 0.91), the classification of DNA histogram (p = 0.81), the DNA index (p = 0.46), and the results of cell cycle analysis in tumors with no aneuploidy (S phase, p = 0.23; S + G2M, p = 0.62) were of no prognostic significance. For squamous cell lung cancer, multivariate analyses showed that increasing American Joint Committee on Cancer stage (p = 0.003) and increasing DNA index (p = 0.009) were of independent (negative) prognostic significance.

Adult↗

PubMed1993

Partial mastectomy without radiation is adequate treatment for patients with stages 0 and I carcinoma of the breast.

The treatment of potentially curable carcinoma of the breast has changed from one operation, radical mastectomy, to a flexible approach. At the Cleveland Clinic, we use four types of treatment for primary potentially curable carcinoma of the breast (Stages 0, I and II)--modified radical mastectomy, simple mastectomy, partial mastectomy with postoperative adjuvant radiation therapy and partial mastectomy without radiation therapy. The latter treatment (partial mastectomy without adjuvant radiation) is controversial. We recommend this procedure for patients with T(is) and T1 carcinomas that appear to be localized, without lymph node metastases, Stages 0 and I disease. The overall and disease-free survival rates are similar to those of patients having modified radical or partial mastectomy with radiation. Local recurrence is slightly higher at five years (11.0 percent) as compared with the other procedures, but at ten years, is only 16.1 percent, a figure comparable with patients having partial mastectomy with radiation (14.4 percent). For patients with Stages 0 and I carcinoma of the breast, the addition of postoperative radiation therapy after partial mastectomy seems to be unnecessary.

Breast Neoplasms↗

PubMed1992

Magnetic resonance imaging lesion enlargement in multiple sclerosis. Disease-related activity, chance occurrence, or measurement artifact?

Magnetic resonance imaging (MRI) may demonstrate disease activity in a number of ways in patients with multiple sclerosis. Newly appearing MRI lesions, gadolinium-enhancing lesions, and enlargement of preexisting lesions are frequently taken as evidence of disease activity. Furthermore, serial MRI studies have been stated to be more sensitive than repeated neurologic examinations in detecting disease activity. We assessed the validity of using lesion enlargement as a measure of disease activity by repeatedly measuring the area of all MRI lesions in four patients with multiple sclerosis. The size-frequency distribution in all patients was similar, with 80% of the lesions measuring less than 0.67 cm2. The median coefficient of variation for three successive lesion measurements was inversely related to lesion area, ranging from 22.6% for the more common smaller lesions (less than 0.67 cm2) to 12.1% for larger lesions. Based on these coefficients of variation, a change in a particular lesion exceeding 45.2% for a baseline lesion smaller than 0.67 cm2 and 24.2% for a baseline lesion greater than or equal to 0.67 cm2 should be required to exclude a change due to measurement variability. It remains necessary to determine the number of lesions that must change when multiple lesions are present in the baseline MRI to reliably exclude chance occurrence when establishing MRI-evident disease activity. Guidelines for determining these criteria are presented, as are the limitations inherent in the statistical model employed to make these determinations.

Humans↗

PubMed1992

Significance of perioperative blood transfusions in patients undergoing resection of stage I and II non-small-cell lung cancers.

Perioperative blood transfusions (BT) have been reported to reduce survival in patients undergoing curative resection of lung cancers. It is postulated that a state of BT-mediated immunosuppression favors the proliferation of tumor cells not resected during surgery. To evaluate this hypothesis and to determine factors influencing the administration of BT, we retrospectively studied the charts of 127 patients who underwent surgery for stage I and II non-small-cell carcinoma. Thirty (23.6 percent) patients received BT and 97 (76.4 percent) did not. Sex, age, race, smoking history, size and stage of the tumor, histology, extent of resection and preoperative hemoglobin values were analyzed. Only age (p = 0.01) and preoperative hemoglobin values (p less than 0.01) were related to transfusion status. Neither survival nor event-free survival differed significantly between the two groups (p = 0.29 and 0.26 respectively). Our results do not support the hypothesis that perioperative BTs have a significant detrimental effect on survival. A prospective study could clarify this controversial issue; however, such a study would be complex considering the multiple variables that affect survival in patients with non-small-cell lung cancers.

Age Factors↗

PubMed1991

Alternating sequential intracarotid BCNU and cisplatin in recurrent malignant glioma.

The authors entered 43 patients with recurrent malignant glioma in a trial of alternating sequential intracarotid BCNU and cisplatin. Protocol design was alternating courses of BCNU (2 doses, 300 to 400 mg each) and cisplatin (2 doses, 150 to 200 mg each) each at 4-week to 6-week intervals. Eight of 40 patients (20%) evaluable after the first course of BCNU showed partial or minor response. Only 18 patients were evaluable after the first course of cisplatin, and 5 were evaluable after the second course of BCNU. Median survival was 9 months (range, 2 weeks to 6 years). Cerebral or ocular toxicity unique to this method of chemotherapy administration and failure to show clinical improvement were the most common reasons for removal from study. Because of the high attrition rate, the authors were unable to determine a meaningful response to alternating sequential BCNU and cisplatin or to test the clinical degree of cross-resistance to these agents in human malignant glioma.

Adult↗

PubMed1991

Phase I trial of natural human interferon beta in metastatic malignancy.

A phase I trial of natural human beta-interferon (nHuIFN-beta) was initiated to evaluate its biological activity, maximum tolerated dose, and toxicity in patients with refractory malignancies. nHuIFN-beta was administered to successive groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks. Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 x 10(6) units/m2. Thirty-five patients were entered, and 34 patients were evaluable for toxicity, immunomodulatory, and antitumor effects. Toxicity was mild to moderate and included fever and chills, fatigue, arthralgias, nausea, transient renal and hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and no responses were seen. Significant immunological changes included the following: an increase in natural killer activity on day 5 when compared to pretreatment values (P less than 0.01) and an increase in activated T-cells (CD3+/HLA-DR+) with increasing doses of nHuIFN-beta (P less than 0.01). Pharmacokinetic data demonstrated a short alpha half-life of 12.1 +/- 2.5 (SE) min and a beta half-life of 129.7 +/- 14.7 min. Neutralizing serum antibodies were detected in 2 of 27 patients receiving nHuIFN-beta. In conclusion, toxicity of nHuIFN-beta given twice weekly was moderate, and further dose escalation is possible. The immunological changes and pharmacokinetic behavior of nHuIFN-beta resemble those reported with rHuIFN-beta ser.

Adult↗

PubMed1991

The dependence of proton longitudinal and transverse relaxation times on cell-cycle phase: mouse MCA-transformed 10T1/2 TCL-15 cells.

Attempts to determine proton NMR longitudinal relaxation times (T1) as a function of cell-cycle stage using cells synchronized by chemical methods have yielded conflicting results (P. T. Beall, C. F. Hazlewood, and P. N. Rao, Science 192, 904 (1976); R. N. Muller et al., FEBS Lett. 114, 231 (1980); D. N. Wheatley, et al., J. Cell Sci. 88, 13 (1987]. This has raised the question whether a true dependence of T1 on cell-cycle phase exists. In the present study, the centrifugal elutriation technique was used to obtain relatively pure, synchronized cell populations of TCL-15 cells (a methylcholanthrene-transformed line of mouse 10T1/2 cells) for measurement of proton NMR relaxation rates. This technique provides a means to procure synchronized cell populations without the use of chemical agents as in the above-cited investigations and therefore avoid possible effects caused by the chemical agents of the NMR relaxation processes. Both T1 and the transverse relaxation time, T2, of water protons in synchronized-cell pellets obtained in this study, exhibited a dependence on cell-cycle phase at least for the first half of the cell cycle (G1 to S). Cells in G1 phase exhibited quantitatively higher T1 and T2 relaxation times compared to those measured for cells in mid S phase. Such changes were found to correlate with changes in water content. The distribution of cell-cycle phases of each cell population was determined by the DNA histogram using flow cytometric methods. Possible relaxation mechanisms which may contribute to the cell-cycle-specific phenomena of the intracellular T1 and T2 times are discussed.

Animals↗

PubMed1991

The response of the KHT sarcoma to radiotherapy as measured by water proton NMR relaxation times: relationships with tumor volume and water content.

The potential application of magnetic resonance imaging (MRI) to predict tumor response to radiotherapy is investigated. The water proton spin-lattice and spin-spin relaxation times (T2 and T2, respectively) of murine sarcomas (designated KHT) were measured shortly after excision. This study has demonstrated significantly different responses in T1 and T2 between the control and the irradiated tumors at various times following single doses of X rays. Quite generally, the changes in relaxation times correlated with the changes in tumor water content, indicating that the MR relaxation-time probes are fairly sensitive to radiation-induced edema and dehydration. The possible relationships between the T1 and T2 responses and radiobiological effects such as those on tumor blood flow, vascular permeability, physiological state of cells, and cell death are discussed. It is conceivable that the findings obtained from this investigation could be extended to in situ studies for potential applications in clinical radiotherapy.

Animals↗

PubMed1991

Tympanic membrane temperatures compared to rectal and oral temperatures.

One hundred thirty-seven children at the Cleveland Clinic Foundation were enrolled in a study comparing the accuracy and acceptability of tympanic membrane temperatures taken with Thermoscan to rectal or oral temperatures taken by IVAC electronic thermometers. The mean age of the rectal/ear group was 1.2 +/- 0.86 years (range 0.08-5.0 years) with 22 females and 21 males. The mean age of the oral and ear group was 9.0 +/- 4.24 years (range 3-18 years) with 44 females and 50 males. Significantly large (p less than 0.01) correlation coefficients were present between temperatures in the left ear and right ear (0.92), rectal and mean ear (0.77) and oral and mean ear (0.68). The temperature difference between mean ear and rectal measurements was -1.1 degree +/- 0.51 degree C and the temperature difference between the mean ear and oral measurements was -0.20 degrees +/- 0.59 degrees C. A relative lack of correlation between ear and oral temperatures was noted with flat tympanograms, otoscopically diagnosed middle ear effusion, and with red-white or red tympanic membranes. However, small subgroup sizes (6-16) may have contributed to this lack of correlation. Parents and physicians were impressed by the 2.5 second speed of the new technique. However, younger children were nearly as likely to resist and cry with ear as with rectal temperatures. Parents were comfortable with the ease, cleanliness and safety of ear temperatures. While these data indicate a strong correspondence of ear temperatures with oral and rectal temperatures, parents were not as confident of ear temperatures' accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Renal cell carcinoma with inferior vena cava tumor thrombi.

Renal cell carcinoma is a unique neoplasm because of its common propensity to propagate into the renal vein and inferior vena cava (IVC) as tumor thrombus. Historically, the surgical difficulties encountered in removal of these cancers limited the ability of a single institution to obtain experience with large numbers of instances. Between January 1956 and July 1987, 68 patients with renal cell carcinoma extending into the IVC or right atrium underwent radical nephrectomy with vena cava thrombus extraction at the Cleveland Clinic. Twenty-five patients had partial resection of the IVC with reconstruction. Fifteen patients had partial resection and reconstruction of the IVC; however, because of narrowing of the infrarenal IVC, persisting bland thrombus in the proximal IVC or iliac veins or concern regarding postoperative pulmonary emboli, the infrarenal IVC was either ligated or clipped. Seven patients underwent cavectomy with division of the IVC. A right atriotomy was performed upon 14 patients and cardiopulmonary bypass was used in 20 patients, with 17 also having deep hypothermic circulatory arrest. The tumor thrombus was removed intact in 64 per cent of the patients and in multiple small fragments ("piecemeal") in 36 per cent of the patients. The mortality rate was 7 per cent. Survival was examined relative to extent of vena caval thrombus. Patients with extension into the atrium had a significantly worse prognosis than those with other levels of vena caval involvement. Other factors, such as lymph node status, perinephric fat involvement, resection of IVC and intact or "piecemeal" extraction, did not influence the survival rate. Patients with pre-existing metastases preoperatively had an extremely poor survival rate. The techniques now available for surgical resection of all levels of tumor thrombus of the IVC make resection feasible in most patients. In our opinion, the addition of deep hypothermic circulatory arrest has been a significant advance.

Carcinoma, Renal Cell↗

PubMed1990

Nonsquamous cell malignancies of the paranasal sinuses.

Nonsquamous cell malignancies represent half of paranasal sinus cancers. Since 1975, 103 patients have been treated at The Cleveland Clinic Foundation for sinus malignancies. Forty-nine patients had nonsquamous cell malignancies: 12 (25%) sarcoma, 10 (20%) adenoid cystic carcinoma, 9 (18%) adenocarcinoma, 9 (18%) lymphoma, and 9 (18%) miscellaneous tumors. Ten patients presented with T1 or T2 disease at the primary site, 16 with T3, and 23 with T4. Ten patients had primary ethmoid malignancies; the remainder of the tumors originated in the maxillary sinus. Five patients had evidence of regional or distant metastases at presentation. Twelve patients were free of disease after initial management. Three patients with recurrent disease were salvaged with additional therapy. Two patients died of complications in the immediate postoperative period. Patients with less extensive primary lesions have an improved prognosis. Survival was similar for the different histologic diagnoses.

Adenocarcinoma↗

PubMed1990

Supplementary motor seizures mimicking pseudoseizures: some clinical differences.

Supplementary motor seizures (SMS) are among the group of frontal lobe seizures that may often be misdiagnosed as pseudoseizures (PS). We designed this study to determine the value of clinical phenomena in distinguishing between the two. In a series of patients with SMS, we identified those with symptoms mimicking PS and compared the clinical phenomena with those of clinically similar PS. We found that SMS are short in duration, stereotypic, tend to occur in sleep, and often present with a tonic contraction of the upper extremities in abduction. This sign was specific for SMS, particularly when occurring at the onset. Conversely, PS are long in duration, nonstereotypic, and occur in the awake state. We conclude that clinical phenomena may be useful in distinguishing PS from SMS, although the final diagnosis must be documented by neurophysiologic means.

Diagnosis, Differential↗

PubMed1990

Phase I trial of continuous infusion recombinant interleukin-2 and intermittent recombinant interferon-alpha 2a: clinical effects.

A phase I trial of high-dose continuous infusion rIL-2 over 5 days and i.m. recombinant human interferon-alpha (rHuIFN-alpha 2a) three times weekly in 23 patients with advanced malignancy has been completed. Cohorts of patients were treated at three different dose levels: rIL-2 3.0 x 10(6) u/m2 plus rHuIFN-alpha 2a either 5.0 or 10.0 x 10(6) u/m2, and rIL-2 4.5 x 10(6) u/m2 plus rHuIFN-alpha 2a 5.0 x 10(6) u/m2 over 4 weeks. Dose-limiting toxicity consisted of pulmonary and neurologic side effects, and the maximal tolerated dose was 3.0 x 10(6) u/m2 on days 1-5 or rIL-2, and 10.0 x 10(6) u/m2 three times weekly of rHuIFN-alpha 2a. Four partial responses (renal carcinoma, three; endometrial carcinoma, one) were seen. In conclusion, toxicity of this schedule of rIL-2 and rHuIFN-alpha 2a was significant, but manageable. Further investigation is needed to define the antitumor activity of this combination.

Adult↗

PubMed1990

Risk factors for early readmission among veterans.

This study was undertaken to identify demographic, clinical, and social risk factors for early readmission in the veteran population. Readmissions within 30 days of discharge were considered "early." A randomly selected 50 percent sample of 6,317 veterans discharged consecutively from one Department of Veterans Affairs medical center (VAMC) was used to build a logistic regression model for early readmission. Of these patients, 22 percent had early readmissions. The adjusted odds ratios (OR) of greater magnitude for early readmission (p less than .05) were associated with discharge from a geriatrics/intermediate care bed (OR = 2.75 relative to medical ward), discharge diagnosis of a chronic disease (OR = 2.03-2.67 relative to acute or self-limiting disorders), and two or more surgical procedures performed during the index admission (OR = 1.87 relative to no surgery). Increasing distance from the VA hospital and increasing age also added readmission risk (OR = 1.18 and 1.10, respectively). Length of stay and the social risk factors of marital status and place of disposition were not sufficiently predictive to enter the model. The model was validated successfully on the second 50 percent sample of patients. We conclude that clinical and demographic factors are more predictive of early readmission than are social factors. Early readmission models could be used to improve VA discharge planning and to focus quality assurance and utilization review efforts on providers whose early readmission rates exceed those predicted by the models.

Adult↗

PubMed1989

Phase I clinical trial of interleukin 2 and alpha-interferon: toxicity and immunologic effects.

Because recombinant interleukin 2 (rIL-2) and recombinant alpha-interferon (rIFN-alpha) exhibit synergistic antitumor activity in C3HMT1820 T-cell lymphoma and B16 melanoma tumor systems, we have performed a Phase I study of this combination in 55 patients with advanced malignancies for whom no standard therapy exists. Successive groups of greater than or equal to 4 patients have been entered into 12 dose levels (1A-3D), with dose levels 1-3 referring to doses of rIL-2 of 0.1, 0.5, and 2.0 x 10(6) units/m2, respectively, and dose levels A-D referring to doses of recombinant human alpha 2a-interferon (rHuIFN-alpha 2a) of 0, 0.1, 1.0, and 10.0 x 10(6) units/m2. Both agents were given on Mondays, Wednesdays, and Fridays, with rIL-2 being given as i.v. bolus injections and rHuIFN-alpha 2a being given intramuscularly. Myelosuppression was dose-limiting and was related primarily to the dose of rHuIFN-alpha 2a. The maximum-tolerated dose level was reached at a dose of rIL-2 of 2.0 x 10(6) units/m2 and of rHuIFN-alpha 2a of 10.0 x 10(6) units/m2 (dose level 3D). At this dose level, 3/6 patients developed grade 3 neutropenia (absolute granulocyte count less than 1 x 10(9)/liter). Myelosuppression was transient, with no documented infections being associated with neutropenia. Hypotension was mild; a single patient was treated with a vasopressor, but all other cases of hypotension responded to fluid administration. No significant pulmonary toxicity was produced. Fever, chills, and malaise were universal but not dose-limiting. Three partial responses and one minor response were observed in patients with malignant melanoma, renal cell carcinoma, and breast cancer. Immunological studies suggested that natural killer activity was related to both the dose of rIL-2 and the dose of rHuIFN-alpha 2a, with natural killer activity being positively related to the dose of rIL-2 and maximal at the lowest dose of rHuIFN-alpha 2a of 0.1 x 10(6) units/m2.

Adult↗

PubMed1989

Infant sleep and bedtime cereal.

We studied whether feeding infants rice cereal before bedtime promotes their sleeping through the night. One hundred six infants were randomly assigned to begin bedtime cereal feeding (1 tablespoon per ounce in a bottle) at 5 weeks or at 4 months of age. Caretakers recorded the infant's sleep from age 4 to 21 weeks for one 24-hour period per week. Sleeping through the night was defined as sleeping at least 8 consecutive hours, with the majority of time being between the hours of midnight and 6 AM. The results were also reviewed changing the requirement from 8 hours to 6 hours. There was no statistically significant trend or a consistent tendency of one group to have a higher proportion of sleepers than the other. Therefore, feeding infants rice cereal in the bottle before bedtime does not appear to make much difference in their sleeping through the night.

Clinical Trials as Topic↗

PubMed1989

Neoadjuvant intra-arterial chemotherapy in the treatment of advanced transitional cell carcinoma of the bladder: results and followup.

The long-term results of regional chemotherapy plus intra-arterial cisplatin with or without doxorubicin as an adjuvant before cystectomy and urinary diversion in patients with invasive transitional cell carcinoma of the bladder were evaluated. A total of 27 patients with T3aNxMo (8), T3bNxMo (14) and T4NxMo (5) disease participated in a phase II trial completed in 1985. Of the patients 19 received cisplatin and doxorubicin intra-arterially, and cyclophosphamide intravenously, and the remaining 8 received 70 to 100 mg. per m.2 cisplatin intra-arterially. A total of 19 patients underwent cystectomy after chemotherapy. Patients in this group had a pathological complete response (no evidence of disease after surgical restaging) or the presence of residual disease at operation that could (surgical complete response) or could not (pathological partial response) be completely resected. Of the 19 patients undergoing cystectomy surgical complete response was observed in 47.4%, pathological complete response in 26.3% and pathological partial response in 26.3%. At a median followup of 27 months for the group 66% of the patients with a surgical complete response, 100% with a pathological complete response and 40% with a pathological partial response were alive with no evidence of disease. The over-all survival for patients with a pathological or surgical complete response is 76.9%. In the patients not operated upon because of persistent or advanced disease after chemotherapy survival was brief (less than 4 months). Prolonged survival in patients achieving a pathological or surgical complete response with neoadjuvant chemotherapy occurs, and this modality may have a role in patients with invasive tumors.

Aged↗