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Biomedical subjects

D Salk

Publications and source records attributed to D Salk.

At least 19 recordsLinked to original sources
PubMed1996

Radioimmunoscintigraphy in patients with early stage cutaneous malignant melanoma.

UNLABELLED: CT and MRI examinations remain relatively insensitive for the detection of metastatic melanoma lesions, especially those of regional lymph nodes. Imaging cutaneous malignant melanoma patients with the Fab fragment of monoclonal antibody (MAb) NR-ML-05 labeled with 99mTc has been reported to increase the accuracy of staging. Our purpose in this study was to assess the sensitivity of 99mTc-labeled NR-ML-05 in detecting the spread of melanoma. METHODS: Twenty-six adult cutaneous malignant melanoma patients were enrolled in this study and were followed for 6 to 60 mo after radioimmunoscintigraphy. At the time of imaging, 20 patients had their primary lesions resected, whereas the remaining 6 patients had their primary lesions intact. RESULTS: Radioimmunoscintigraphy correctly detected 8 of 18 suspicious lesions as malignant, as well as 4 additional malignant lesions which had not been suspected previously. Radioimmunoscintigraphy also correctly identified 8 of the 18 suspicious lesions as benign. Two of the 18 suspicious lesions were found to be false negatives. The overall lesion sensitivity of radioimmunoscintigraphy was 86%. CONCLUSION: Twenty-four of the 26 patients were correctly staged by radioimmunoscintigraphy. The accuracy of staging of cutaneous malignant melanoma patients by clinical and or radiologic examinations (73%) was greatly improved with the use of radioimmunoscintigraphy (93%). These results suggest that radioimmunoscintigraphy may be a clinically useful adjunct to the current armamentarium for guidance of medical, and particularly surgical, therapy of cutaneous malignant melanoma patients.

Adult↗
PubMed1994

Human anti-mouse antibody suppression with cyclosporin A.

BACKGROUND: Cyclosporin was used in an attempt to suppress the formation of human antimouse antibody (HAMA) after administration of murine monoclonal antibodies. METHODS: Thirteen patients were given oral cyclosporin (8.6-15 mg/kg/day) starting 2 days before administration of technetium-99m (99mTc) labeled F(ab')2 (3 patients) or Fab (10 patients) murine antibody fragment. Six to nine days later, patients received either rhenium-186 (186Re)-labeled F(ab')2 or an intact antibody. Cyclosporin was continued for 14 days after the second antibody administration. RESULTS: Five patients (38%) did not develop elevated HAMA titers for up to 8 weeks after antibody administration. These five patients had a median cyclosporin concentration of 726 ng/ml, while the eight patients who developed HAMA had a median cyclosporin level of 364 ng/ml. In contrast, when not given cyclosporin, 86% (24/28) of patients developed HAMA after receiving two doses of F(ab')2, and 100% (15/15) developed HAMA after receiving Fab followed by intact antibody. Toxicity from cyclosporin included elevation concentrations of bilirubin and creatinine, and increased blood pressure, which rapidly resolved after the cyclosporin was discontinued. CONCLUSIONS: This study demonstrates that cyclosporin given from 2 days before until 2 weeks after administration of either a F(ab')2 or intact murine antibody can suppress HAMA formation. This strategy may permit administration of repeated doses of murine-antibody-based radioimmunotherapy.

Animals↗
PubMed1993

Rhenium-186-labeled chimeric antibody NR-LU-13: pharmacokinetics, biodistribution and immunogenicity relative to murine analog NR-LU-10.

A mouse-human chimeric monoclonal antibody (NR-LU-13), with the same pancarcinoma antigen recognition site as a previously studied murine monoclonal antibody (NR-LU-10), was radiolabeled with 186Re using a bifunctional chelate. Nine patients (ages 31-81 yr) with metastatic adenocarcinoma received 186Re NR-LU-13. A single intravenous dose of 42 mg NR-LU-13 labeled with 25 mCi/m2 (two patients) or 60 mCi/m2 (seven patients) was administered. Mean serum disappearance half-time values for the chimeric 186Re NR-LU-10). Fifty percent of the radiolabel was excreted in the urine by 6 days. Tumor localization was demonstrated by gamma camera imaging in seven of nine patients. The percent injected dose per gram in a single tumor biopsy specimen was 0.003% at 72 hr postinjection. Absorbed dose to bone marrow was 1.5 +/- 0.7 rads/mCi and resulted in reversible myelosuppression in five of six evaluable patients who received 60 mCi/m2: median WBC nadir = 2500/microliters; median platelet nadir = 85,500/microliters. Low grade fever, nausea, slight elevations of liver function tests and mild allergic reactions were seen in some patients. The chimeric antibody elicited low levels of anti-NR-LU-13 antibody in six of eight evaluable patients (75%), in contrast to NR-LU-10 which elicited higher levels of human anti-mouse antibody in all patients. This pilot study demonstrates the ability of the chimeric antibody to target tumors with reduced (but not absent) immunogenicity and delayed clearance relative to the murine antibody.

Adenocarcinoma↗
PubMed1992

Detection and staging of small cell lung carcinoma with a technetium-labeled monoclonal antibody. A comparison with standard staging methods.

Tumor-associated radiolabeled monoclonal antibodies (MoAb) can detect neoplasms in a variety of settings. The authors conducted a study comparing the ability to detect and stage small cell lung carcinoma by using a Tc-99m labeled monoclonal antibody (NR-LU-10 Fab) (NeoRx Corp, Seattle, WA) with standard staging methods. Standard staging included a physical examination, chest x-ray, a battery of radionuclide scans and/or computerized tomographic studies (head, abdomen, and bone), and bone marrow examination. A total of 22 comparisons were performed in 17 patients (five patients had reevaluations after therapy). Fifty-four (74%) of the 73 lesions defined by standard staging were detected by the radiolabeled MoAb. Seven of eight patients (88%) classified by standard staging as having "limited stage" disease on presentation were concordantly "limited stage" by radioimmunoimaging. One patient deemed "limited stage" by standard staging was correctly upstaged (bone marrow involvement) as a result of the radiolabeled MoAb. Two patients found to have extensive disease at diagnosis were characterized as "limited stage" by the MoAb, for an overall staging accuracy of 0.88. Thirteen of 19 missed lesions were smaller than 2 cm (10 were smaller than 1 cm; 3 measured 1 to 2 cm). This comparative study shows that radioimmunoimaging by Tc-99m labeled NR-LU-10 Fab antibody is capable of complementing standard staging methods used in the evaluation of small cell lung carcinoma.

Carcinoma, Small Cell↗
PubMed1991

A technetium-labeled monoclonal antibody for imaging metastatic melanoma.

Twenty patients with histologically proven metastatic melanoma were scanned with a 99mtechnetium (99mTc)-labeled melanoma antibody to determine the detection rate of known malignant lesions and to evaluate the antibody's ability to discover occult metastases. Isotope localization in different organs was as follows: liver 100%, bone 100%, subcutaneous lesions 80%, lymph nodes 54%, and lung 33%. Four unsuspected bone lesions and 16 occult subcutaneous lesions were found. False positive lesions were noted in two instances--one benign thyroid adenoma, and one arthritic bone lesion. One patient developed an atypical serum sickness reaction with a rash and arthralgias that responded rapidly to treatment. The 99mTc antimelanoma antibody is a safe and effective method to detect metastatic melanoma. It has potential use for screening newly diagnosed melanomas that carry an increased risk of recurrence.

Aged↗
PubMed1991

Radionuclide imaging of bone marrow metastases with a Tc-99m labeled monoclonal antibody to small cell lung carcinoma.

The detection of metastatic disease confined to the bone marrow compartment has in the past been technically limited. We have identified excellent imaging of bone marrow metastases during the evaluation of a Tc-99m labeled monoclonal antibody (NR-LU-10 Fab) (NeoRx Corp., Seattle, WA). This occurred during a study to assess the monoclonal antibody's ability to detect sites of small cell cancer (primary and metastatic). The study by design compares areas seen by the monoclonal antibody scan with those found by standard staging methods in patients with small cell lung cancer. Standard staging included chest x-rays, bone scans, CT studies of the abdomen, and histologic examination of the bone marrow. Fifteen patients have been evaluated, four on two occasions, for a total of 19 monoclonal imaging studies. Metastasis to the marrow compartment was identified by the monoclonal imaging in all patients whose bone marrow biopsies were positive for small cell carcinoma, and it was primarily responsible for the eventual detection of extensive disease (marrow involvement) in one patient. Thus it appears that compartmental bone marrow imaging for metastatic disease is possible with immunoscintigraphy.

Bone Marrow↗
PubMed1990

Staging non-small cell carcinoma of the lung using technetium-99m-labeled monoclonal antibodies.

A technetium-labeled monoclonal antibody was administered to 52 patients with non-small cell lung carcinoma, either to stage the mediastinum preoperatively or to detect distant metastases. Results from planar and tomographic imaging are compared to CT and histologic confirmation. Differences in detection rates and predictive values between imaging modalities are discussed. The authors conclude that imaging with a technetium-labeled monoclonal antibody is safe and accurate and may be useful for staging patients with either operable or inoperable non-small cell lung cancer.

Adult↗
PubMed1989

Immunologic memory induced at birth by immunization with inactivated polio vaccine in a reduced schedule.

One hundred forty-one healthy newborns were immunized 24 hours after birth with one dose of inactivated polio vaccine (IPV) of enhanced potency. Following the administration of a second vaccine dose six months later, a considerable proportion of babies responded with neutralizing antibody (NA) to the three poliovirus types. The very rapid occurrence and high antibody titer were indicative of an anamnestic response. Twenty-one infants who still had NA less than 1:4 to one-more poliovirus types after the second vaccine dose responded with very high NA values 7-10 days after a supplementary dose of IPV. It appears that IPV of enhanced potency administered at birth is apt to induce immunologic memory, which should provide the basis for protection against paralytic poliomyelitis in case of exposure to wild poliovirus later in life.

Humans↗
PubMed1989

Technetium-99m labeled monoclonal antibodies in the detection of metastatic melanoma.

Twenty-six stage II/III malignant melanoma patients with 321 measurable metastatic lesions were imaged using Fab fragments of an IgG murine monoclonal antibody labeled specifically with 10-30 mCi Tc-99m with a bi-functional chelating method (NeoRx, Seattle, WA). There were no side effects or adverse reactions. Immunoscintigraphy demonstrated 66.6% of lesions larger than 1 cm and 92.5% of lesions larger than 3 cm. Most frequently detected metastases were in lymph nodes, subcutaneous areas, and bone. Of lesions less than 1 cm, 23.6% were detected if superficial cutaneous lesions were excluded. The smallest detectable lesion was 4 mm. Twenty-one additional clinically unsuspected sites were visualized in 12 of the 26 patients studied. Of these, 56% were confirmed as metastasis by other tests. There were apparent nonspecific localizations owing to other causes, including fracture, varicosities, skin abscess and pneumonitis. Increased experience in image analysis facilitates correct interpretation of these localizations. This study demonstrates that imaging with Tc-99m labeled antibody fragments detects melanoma lesions in organs routinely surveyed and in other areas not routinely assessed by other imaging techniques. The procedure is readily performed and safe. The principal advantage of the test is its ability to survey the entire body and all organs with a single test. Its principal limitation, in common with other diagnostic imaging procedures, is its poor sensitivity for detecting lesions less than 1 cm.

Adult↗
PubMed1988

Nonfluorescent dicentric Y in males with hypospadias.

We report three boys with severe hypospadias and bilaterally palpable testes with abnormalities of the Y chromosome detected by Q-banding. Severe hypospadias with palpable testes is an unusual presentation for Y chromosome abnormalities. Based on our experience, we recommend that boys with this phenotype undergo complete cytogenetic evaluation, because Y chromosome abnormalities prompt additional management concerns.

Humans↗
PubMed1988

Mosaicism for ring 19: a case report.

A male with mosaicism for ring 19 presented with a complex cardiac malformation, microcephaly and minor dysmorphic features. Intellectual development has been within normal limits. This chromosome aberration has been reported only twice before and no clear phenotype-karyotype correlations are recognized.

Abnormalities, Multiple↗
PubMed1988

Polio immunization policy in the United States: a new challenge for a new generation.

The primary reason that live poliovirus vaccine is recommended in the United States today is because it may immunize contacts who have not otherwise chosen to be vaccinated. This policy places contacts at risk of paralysis from an untested, unlicensed "spread virus" vaccine and places infants at risk for an unproven, theoretical benefit to others, not themselves. The licensed killed poliovirus vaccine provides equivalent protection to those vaccinated, with no risk to recipients or contacts. The preceding analysis by Hinman, et al, is an interesting exercise in modeling, but many of their assumptions are open to question. Their sweeping conclusions are not justified by the type of analysis performed, which should yield an overall assessment of a decision environment not a single optimal choice. No measure of perceived social consequence or patient attitude is included, although this is of central importance today. Their report lends an aura of credibility to one conclusion, but this credibility is illusory at best. The major social issue today is not which vaccine to use, but how should polio immunization policy be evaluated.

Child↗
PubMed1987

Trisomy Xq in a male: the isochromosome X Klinefelter syndrome.

We report on a male with trisomy Xq resulting from an isochromosome Xq which is preferentially inactivated: 47,XY,+i(Xq). Six previous cases have been reported. These patients are similar to patients with classical Klinefelter syndrome (47,XXY) in that they have infertility, decreased masculinization, gynecomastia, and elevated luteinizing hormone (LH) and follide stimulating hormone (FSH) levels. They may differ in having average intelligence and normal to short stature. These findings indicate that extra copies of the long arm of X have phenotypic expression, even though activated only in early development.

Adolescent↗
PubMed1987

Duplication 7p in a family with t(7;11): association with anomalies of the anterior cranial base.

Duplication 7p has been observed in association with several balanced translocations. Of eight previously recorded cases, only one exhibited duplication of the entire short arm of chromosome 7. We report on a newborn infant with multiple congenital anomalies and an abnormal chromosome constitution: 46,XX,-11,+der(11),t(7;11) (p11.1;p15.5)mat. The proposita appeared to possess an isolated duplication of the entire short arm of 7. The patient died at age 4 days because of respiratory complications of meconium aspiration. Clinical and postmortem findings included craniocerebral asymmetry, craniosynostosis of a lambdoid suture, arhinencephaly, hypertelorism, anomalies of the ethmoidal portion of the cranial base, large anterior fontanelle, low set ears, ventricular septal defect (VSD), dysplastic tricuspid and pulmonic valves, hypoplastic genitalia, bilateral dislocated hips, and other minor limb malformations.

Abnormalities, Multiple↗
PubMed1987

Interphase cell flow cytometry as a means of monitoring genomic size in normal and neoplastoid cell cultures.

The DNA specific fluorescence of mass cultures and clones derived from human skin and bladder tumor tissue was assayed by flow cytometry. In order to detect and quantitate small fluorescence intensity changes, cytogenetically defined triploid or diploid human fibroblast strains were cocultivated, harvested, and stained with the cell strain of unknown karyotype. The triploid standard (derived from human abortus tissue) proved chromosomally unstable at high passage level. Fifteen male, female, and 45,X strains displayed target-to-standard cell fluorescence ratios commensurate with their respective chromosome constitutions. Interstrain variation was highest among the 45,X strains, although mosaicism could not be detected by conventional cytogenetics. Interclonal fluorescence variation was two- to ten-fold higher among the tumor-derived clones tested. Chromosome counts and subcloning experiments indicate that this increased fluorescence variation is due to genome size variation. The clonal evolution of genome size differences was observed in subclones of chromosomally divergent parental clones. These observations suggest that well controlled flow cytometry can adequately resolve subtle degrees of genome size variation in cultivated human cells. The technique is especially suited for monitoring genome size changes in cultivated tumor cells.

Cell Separation↗
PubMed1985

Induction of DNA polymerase alpha in senescent cultures of normal and Werner's syndrome cultured skin fibroblasts.

DNA polymerase alpha activity was determined following serum stimulation of early and late passages of human diploid fibroblast-like (HDFL) cultures derived from apparently normal donors (two strains) and from a patient with Werner's syndrome (one strain). Induction of this enzyme was observed in both low passage, actively proliferating cultures and in postmitotic "senescent" cultures from all three strains. The maximal polymerase activity of early and late passage cells of each strain were nearly identical when normalized to the number of cells present. However, the activity of the enzyme was observed to be significantly lower in late passage cultures when normalized to total protein content apparently because of enlargement of the senescent cells. The behavior of Werner derived cells was similar to that of the normal cells. The induction of DNA polymerase alpha in senescent cultures indicates that they retain the capacity to carry out some complex metabolic responses to mitogen stimulation. In addition, these results suggest the possibility that dilution of DNA polymerase alpha and/or other DNA replication factors may play a role in the onset or maintenance of the postmitotic state in the enlarged senescent HDFL cells.

Aphidicolin↗