Search PubMed⌕ Search

Biomedical subjects

D Karp

Publications and source records attributed to D Karp.

At least 19 recordsLinked to original sources
PubMed1994

Progression of basal cell carcinoma through loss of chromosome 9q and inactivation of a single p53 allele.

Basal cell carcinoma (BCC) of the skin represents a unique group of tumors strongly associated with exposure to UV light. Unlike squamous carcinoma of the skin, BCC is generally indolent, noninvasive, and rarely metastatic. To study the involvement of tumor suppressor genes in these neoplasms, we analyzed 36 BCCs for p53 mutations and a subset of these tumors for loss of chromosomes 17p and 9q. Sixty-nine % of sporadic BCCs had lost a 9q allele, with the common area of loss surrounding the putative gene for nevoid BCC or Gorlin's syndrome. Forty-four % (16 of 36) of BCCs had a mutated p53 allele, usually opposite pyrimidine tracts, which is consistent with UV-induced mutations. Surprisingly, only one tumor had lost a 17p allele, and in all BCCs only one p53 allele was inactivated. This is in direct contrast to other epithelial tumors, which usually progress by the inactivation of both p53 alleles.

Adult↗
PubMed1994

Photochemotherapy beyond psoriasis.

Photochemotherapy involves the therapeutic use of nonionizing radiation in combination with a photosensitizing chemical to trigger a photochemical reaction that mediates a beneficial effect. The successful introduction and widespread use of psoralen photochemotherapy (PUVA) in the management of psoriasis was the chief stimulus for recent interest in the therapeutic use of nonionizing radiation in various other dermatoses. This article discusses the expanding spectrum of diseases responding to PUVA therapy. More than 30 conditions such as atopic dermatitis, mycosis fungoides, vitiligo, the photodermatoses, chronic graft-versus-host disease, and granuloma annulare have been successfully treated with oral psoralen photochemotherapy. Various mechanisms of response to treatment are discussed including photoimmunologic effects, selective cytotoxicity, alterations of cell function, and stimulation of melanocytes. Finally, the limitations to the use of PUVA therapy are identified and its future use in other cutaneous and systemic diseases are discussed.

Humans↗
PubMed1994

Wegener's granulomatosis presenting as lower back pain with prostatitis and ureteral obstruction.

A 65-year-old man presented with progressive, severe lower back pain, obstructive uropathy, and weight loss. Examination revealed a large, firm prostate, and laboratory studies included an elevated creatinine, erythrocyte sedimentation rate, and prostate specific antigen level. A chest radiograph displayed multiple nodules and a renal ultrasound demonstrated unilateral hydronephrosis. Biopsies of both the prostate and the lung showed necrotizing granulomas consistent with Wegener's granulomatosis, and the patient had positive cytoplasmic antineutrophil cytoplasmic antibodies. He was treated with cyclophosphamide with resolution of all signs and symptoms, and clearing of his radiograph. Our case represents the rare occurrence of Wegener's granulomatosis presenting as prostatitis and ureteral obstruction.

Aged↗
PubMed1993

Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small-cell lung cancer: The Eastern Cooperative Oncology Group Results.

BACKGROUND: Patients with metastatic (stage IV) non-small-cell lung cancer usually have a poor prognosis and disease refractory to chemotherapy. Three new agents--taxol, merbarone, and piroxantrone--have shown promising antitumor treatment in vitro and in animals. Taxol is an antimicrotubular agent that interferes with mitosis during cell division. Merbarone, a conjugate of thiobarbituric acid and aniline, is a topoisomerase II inhibitor, which thus inhibits DNA synthesis and tumor growth. Piroxantrone, an anthracenedione derivative, is a DNA intercalating agent that has shown potent antitumor activity in animal studies. PURPOSE: Our randomized phase II study was designed to evaluate the efficacy and toxicity of these agents in the treatment of stage IV metastatic non-small-cell lung cancer. METHODS: Eligible patients (119) were randomly assigned to receive one of the three treatments given every 3 weeks: 250 mg/m2 taxol by a 24-hour intravenous infusion, 1000 mg/m2 merbarone by continuous intravenous infusion through a central catheter daily for 5 days, or 150 mg/m2 piroxantrone by intravenous infusion over 1 hour. Patients had received no chemotherapy. Response and toxicity were evaluated every 3 weeks. RESULTS: Twenty-five patients were randomly assigned to receive taxol, 47 to receive merbarone, and 47 to receive piroxantrone. One of 44 assessable patients (2.3%) treated with piroxantrone had a complete response. Rates for partial response were 20.8% (five of 24 patients) and 5.7% (two of 35) for assessable patients treated with taxol or merbarone, respectively. One-year survival rates were 41.7%, 21.6%, and 22.6%, and median survival times were 24.1, 19.9, and 29.3 weeks for taxol, merbarone, and piroxantrone, respectively. These differences were not statistically significant, but this study was not designed to compare survival. In general, toxicity was manageable. With premedication, no anaphylaxis was observed with taxol. The most common toxic effects were leukopenia with taxol or piroxantrone treatment and thromboembolic complications with merbarone. Death directly related to treatment occurred in 4% (one patient), 11.4% (four), and 5% (two) of the assessable patients receiving taxol, merbarone, and piroxantrone, respectively. Cardiotoxicity and neurotoxicity occurred only occasionally in all three arms. CONCLUSION: On the basis of the response rate (20.8% partial response) and 1-year survival rate (41.7%), taxol is an active agent for the treatment of metastatic non-small-cell lung cancer. Merbarone and piroxantrone are relatively inactive. IMPLICATIONS: Further study of taxol is warranted. In future studies, taxol should be combined with other agents, and granulocyte colony-stimulating factor should be used to ameliorate myelosuppression.

Adult↗
PubMed1992

Sequences in both class II major histocompatibility complex alpha and beta chains contribute to the binding of the superantigen toxic shock syndrome toxin 1.

Class II major histocompatibility complex (MHC) molecules present peptides derived from processed antigen to antigen-specific CD4-positive T cells. In addition, class II molecules bind with high affinity another class of antigens, termed superantigens. T cell stimulation by superantigens depends almost exclusively on the V beta segment expressed by the T cell receptor (TCR). Mapping of the superantigen binding site on class II molecules should provide valuable information on how MHC and TCR molecules interact. Recombinant mouse I-A class II molecules expressed on transfected L cells were analyzed for their ability to bind the toxic shock syndrome toxin 1. Polymorphic residues in the alpha helices of both the alpha and beta chains of I-A contributed to quantitative toxin binding, suggesting that the toxin binds to either a combinatorial or a conformational site on class II MHC molecules.

Animals↗
PubMed1991

A phase II study of piritrexim in combination with methotrexate in recurrent and metastatic head and neck cancer.

Thirty patients with recurrent and/or metastatic head and neck cancer were treated with sequentially administered methotrexate (MTX) and piritrexim (PTX). The treatment schedule consisted of intravenous (IV) MTX (50 mg/m2) administered on day 1 and oral PTX (75 mg/m2) administered twice daily on days 8 to 12. Courses were repeated every 21 days with dose escalation in subsequent courses aimed at achieving Grade 1 toxicity. Two patients were not evaluable for response, 5 (17%; 95% confidence interval, 4% to 30%) had a partial response (PR), 10 had stable disease, and 13 had progressive disease. All five responses were seen in patients with regional lymph nodes as measurable disease. The median time to progression for all patients was 1.4 months, and the median survival was 6.7 months. Generally, this regimen was well tolerated with only mild toxicity seen during cycle 1 in the majority of patients. Dose escalation in subsequent cycles was possible in a high percentage of patients. Although the overall response rate and survival figures in this Phase II trial were disappointing, the doses and schedule used in this trial may have been suboptimal as reflected by the low incidence of moderate to severe toxicity. Additional evaluation of this combination of drugs in a more aggressive schedule may be warranted.

Aged↗
PubMed1990

An outpatient anticoagulation protocol managed by a vascular nurse-clinician.

Lifetime anticoagulation has become a therapeutic option for surgical patients with hypercoagulable states or prosthetic arterial bypass grafts. However, physicians may not achieve optimal anticoagulation or may attempt to limit the length of the therapy period because of the perceived morbidity from hemorrhagic complications of Coumadin therapy. A protocol for anticoagulant therapy monitored and regulated by a vascular nurse-clinician was reviewed. Coumadin was prescribed for 1,891 patient-months to 93 patients to maintain their prothrombin time 1.5 to 2 times control (range: 18 to 24 seconds). The mean (+/- SD) prothrombin time for the study population was 19.8 +/- 1.8 seconds. During follow-up, 472 (14%) of 3,479 prothrombin times measured were below the therapeutic range (n = 232) or prolonged (n = 240), prompting an adjustment in the Coumadin dose in 82 (88%) patients. Four patients developed recurrent vascular graft thrombosis while receiving anticoagulation. There were 6 major and 11 minor hemorrhagic complications. Patients with a chronic risk for arterial or venous thrombosis can have out-patient anticoagulant therapy administered at optimal intensity and regulated safely with a low incidence of hemorrhagic and thrombotic events.

Adolescent↗
PubMed1990

Behavioral changes correlated with brain-stem auditory evoked responses in term infants with moderate hyperbilirubinemia.

The purpose of this study was to test the hypotheses that newborn infants with moderate serum bilirubin concentrations have depressed Brazelton scores and increased brain-stem conduction time and that serum bilirubin levels correlate with Brazelton behavior scores and brain-stem auditory evoked response changes. Fifty term infants who were enrolled into either a low serum bilirubin group (less than 8 mg/dl) or a moderate serum bilirubin group (10 to 20 mg/dl) were tested with the Brazelton Neonatal Behavioral Assessment Scale and a brain-stem auditory evoked response test. Partial correlation analysis controlling for phototherapy revealed that increased bilirubin concentration correlated negatively with the Brazelton orientation and with state range clusters and individual Brazelton test items that involve auditory processing. Increased bilirubin concentration correlated with an increased latency of brain-stem auditory evoked response wave 4, 5. An increased interpeak 1-5 (brain-stem conduction time) correlated with the decreased animate visual and auditory item. We conclude that moderate hyperbilirubinemia in term infants affects both infant behavior, as measured by specific components of the Brazelton test, and brain-stem conduction time, as measured by the brain-stem auditory evoked response test.

Arousal↗
PubMed1983

Differentiation patterns in the blastic phase of chronic myeloid leukemia.

The surface antigen phenotype of 30 patients with the blast phase of chronic myeloid leukemia (CML) was determined using a panel of monoclonal antibodies recognizing differentiation antigens of normal myeloid, erythroid, megakaryocyte, and lymphoid cells. Ten patients' cells expressed a phenotype corresponding to an immature myeloid cell and were felt to have "myeloid" blast crisis. None of these myeloid leukemias were TdT+ or responded to vincristine (V) and prednisone (P). Eleven patients expressed a phenotype similar to acute lymphoblastic leukemia cells and probably reflect maturation to an early B lymphocyte. All of these "lymphoid" leukemias were TdT+, and 67% of evaluable patients had a complete response to V and P. One leukemia had the phenotype of an erythroleukemia, one patient's cells expressed the phenotype of megakaryoblastic leukemia, and one leukemia had populations of both myeloid and lymphoid blasts. Six leukemias did not express surface markers characteristic of any lineage and were termed "undifferentiated." This group was heterogeneous with respect to TdT expression, but no patient had a complete response to V and P. Determination of surface antigen phenotype in CML blast crisis thus provides clinically useful information for the structuring of treatment protocols.

Adolescent↗
PubMed1981

Mycobacterium thermoresistibile: a new pathogen for humans.

The first evidence of the potential pathogenicity of Mycobacterium thermoresistibile is presented. This mycobacterium, initially identified as Mycobacterium gordonae, was isolated repeatedly from sputum, a bronchoscopy specimen. and later, an open lung biopsy. The distinctive characteristics are described, including the unique ability of the organism to grow at 52 degrees C.

Bronchi↗
PubMed1981

Reduction of plasma urate levels in the cockerel with polyethylene glycol-uricase.

Uricase from C. utilis and uricase to which polyethylene glycol had been attached were injected into leghorn cockerels in an attempt to lower plasma urate levels. Twenty units of either enzyme reduced urate levels to near zero for 24 hr on initial injection, whereas 10 U were effective for less than 6 hr. After injection with four-weekly doses of enzyme, unmodified uricase was ineffective in lowering plasma urate levels. Polyethylene glycol-uricase, however, was as effective as on the first injection. Both enzyme preparations appear in the lymph shortly after injection into the rat, although polyethylene glycol-uricase appears slightly sooner and maintains a more constant level than uricase.

Animals↗