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Biomedical subjects

D J Perry

Publications and source records attributed to D J Perry.

At least 37 records · Page 2Linked to original sources
PubMed1989

CpG dinucleotides are "hotspots" for mutation in the antithrombin III gene. Twelve variants identified using the polymerase chain reaction.

CpG dinucleotides have been implicated as mutational hotspots in genes that are subject to control mechanisms involving methylation. We have used the polymerase chain reaction to amplify exons 2 and 6 of the human antithrombin III gene and direct sequencing to identify the base replacement in 12 genetic variants. These occurred in individuals with a history of thromboembolic disease due to functional abnormalities of circulating antithrombin: ten had decreased heparin binding and activation, two had decreased inhibitory activity. The amino acid abnormality in ten out of 12 cases had arisen at a CpG dinucleotide; this confirms the CpG sequence as a "hotspot" in the antithrombin gene and explains the observed frequency of occurrence of the same variant antithrombins in diverse populations.

Antithrombin III↗
PubMed1988

Cisplatin and mitoguazone. An induction chemotherapy regimen in advanced head and neck cancer.

The combination of cisplatin 100 mg/m2 every 3 weeks and mitoguazone 500 mg/m2 every week with dose escalation was administered as a 9-week induction regimen to 27 patients with previously untreated Stage III or IV squamous cell carcinoma of the head and neck. This was followed by full-course radiation therapy for unresectable patients or surgery and postoperative radiation therapy for those with resectable disease. Sixteen patients had bulky unresectable disease, and ten were candidates for curative resection at study entry. Of 26 patients evaluable for response to chemotherapy, there were seven complete responses (CR) (five of six pathologically confirmed) and ten partial responses (PR) (65% CR + PR). Toxicity was generally mild with Grade 3 or 4 nausea and vomiting occurring in 15% and diarrhea in 12%. Nineteen percent of the patients developed transient nephrotoxicity (serum creatinine greater than 2), 62% anemia (hemoglobin decrease greater than 2 g/dl), 23% leukopenia (leukocyte count less than 3500 cells/microliters) and 8% thrombocytopenia (platelets less than 50,000 cells/microliters). Anorexia, fatigue, and weight loss occurred in nearly all patients. The median survival time of all patients was 17.5 months; complete responders, 43 months; partial responders, 16 months; and nonresponders, 9 months (P = 0.0025). In a multivariate analysis of stage, primary site, resectability status, response to chemotherapy, and local treatment (surgery plus radiation versus radiation), complete response was the only statistically significant covariate for survival. In Phase II single agent trials, mitoguazone has been shown to have a 15% response rate in head and neck cancer and cisplatin, a 30% to 40% response rate (less than 10% CR). Thus, our results, both complete and overall response rates, were higher than would be expected from either drug alone. A possible mechanism for this high response rate may be mitoguazone-induced cell synchronization. In vitro studies demonstrate the accumulation of tumor cells exposed to mitoguazone in S- and G2-phases of the cell cycle. These results would support further evaluation of mitoguazone in combination to explore the theoretical potentiation of antitumor effects by sequencing with cycle-specific agents.

Adult↗
PubMed1988

Eosinophilia associated with adult T-cell leukemia/lymphoma.

Eosinophilia is associated with a number of disorders including malignancies. A patient is described who had eosinophilia associated with adult T-cell leukemia/lymphoma (ATL) induced by human T-lymphotropic virus type I (HTLV-I). Both tissue and peripheral blood eosinophilia and high titers of HTLV-I antibody were present. The eosinophilia was most likely caused by the malignant cells producing one or more lymphokines. The patient has achieved a durable complete remission from combination chemotherapy. Because durable remissions in ATL are rare with any known therapy and eosinophilia has not previously been associated with ATL, it is possible that the tumor in this patient was derived from a T-cell subset not usually transformed by HTLV-I. ATL is another malignancy now known to cause eosinophilia.

Adult↗
PubMed1988

Clinical predictors of response in metastatic germ cell tumors.

Twenty-two patients with bulky, metastatic germ cell tumors were treated with cyclophosphamide, vinblastine, dactinomycin, bleomycin, and cisplatin (VAB) alternating with VP-16 and vincristine (VV). The overall complete response rate after chemotherapy with or without surgical excision of residual tissue was 63% (14 of 22 patients) with a median survival of 46 months. Five patients are dead of disease progression and three are alive beyond 3 years with only residual radiographic abnormalities. A retrospective analysis of prognostic variables (numbers of sites of disease, tumor marker levels) using two previously published prognosis formulas demonstrated a good correlation between prognostic variables (numbers of sites of disease, tumor marker levels) and the clinical assessment of prognosis based on tumor bulk and tumor marker level. Nevertheless, individual patients with other, unknown prognostic features may be incorrectly evaluated using either established formulas or clinical assessment of tumor bulk.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

PDQ--a database of clinical trials and cancer treatment information.

The National Cancer Institute has developed an online clinical information system known as PDQ (Physician Data Query) to provide physicians with up-to-date information on cancer treatment and to facilitate participation in cancer clinical trials. PDQ is a major component in the National Cancer Institute's goal of reducing cancer mortality 50% by the year 2000.

Clinical Trials as Topic↗
PubMed1988

Keeping up with the cancer literature--PDQ ACCESS.

Physician Data Query (PDQ) (National Cancer Institute [NCI], Bethesda, MD) and CANCERLIT (NCI, Bethesda, MD) are two online cancer information databases. PDQ summarizes current cancer therapy literature into specific treatment recommendations. CANCERLIT is a bibliographic system similar to MEDLINE (National Library of Medicine [NLM], Bethesda, MD) that provides a comprehensive source of literature citations for the field of cancer. In this report, we discuss linking PDQ and CANCERLIT with PDQ ACCESS (NCI, Bethesda, MD)--a custom software package that makes searching the cancer literature easy for the practicing physician unfamiliar with database searching.

Humans↗
PubMed1988

On the penetration of fast charged particles.

We pursue Yang's multiple scattering analysis and develop a wave description of electron penetration which permits the calculation of spatial distributions under realistic conditions. We give special emphasis to the longitudinal part of the problem and illustrate with sample calculations of particular interest to medical physicists.

Electrons↗
PubMed1987

Bone marrow transplantation in a patient with myelodysplasia associated with diffuse eosinophilic fasciitis.

A 34-year-old man with diffuse eosinophilic fasciitis and a hypocellular myelodysplastic syndrome underwent marrow transplantation from an HLA-identical brother. Prompt hematopoietic reconstitution was observed, strongly suggesting that the marrow hypocellularity was caused by neither a serum inhibitory factor nor a microenvironmental disorder. The patient died of disseminated cytomegalovirus infection too early to evaluate the impact of hematopoietic reconstitution on the eosinophilic fasciitis. Nevertheless, marrow transplantation may offer a therapeutic option for those patients with this disorder who develop severe hematopoietic dysfunction and who have a suitable marrow donor.

Adult↗
PubMed1987

Empirical treatment of febrile, neutropenic patients with tobramycin and latamoxef.

One hundred and two febrile episodes in neutropenic patients were treated with intravenous tobramycin and latamoxef. After 48 h latamoxef at 6 g day-1, patients were randomized to continue this regimen or latamoxef at 3 g day-1. Infections responded to these regimens in 67% and 71% of patients, respectively. Two-thirds of the infections which failed to respond were due to coagulase-negative staphylococci in Hickman catheters, a trend which may necessitate the inclusion of additional antibiotics in future empirical regimens. Prolonged prothrombin times due to antibiotic therapy were seen in nine patients but there was only one episode of bleeding and this responded quickly to treatment with vitamin K and fresh frozen plasma. In 35 patients, coagulopathy was present before antibiotics were started, and these cases also responded to vitamin K. The study shows that the response to tobramycin and latamoxef is comparable to other broad-spectrum antibiotic regimens and that a reduction in the dose of latamoxef after 48 h treatment may safely permit cost savings.

Agranulocytosis↗
PubMed1986

Right heart obstruction due to intracavitary prolymphocytic leukemia.

A 52-year-old woman with prolymphocytic leukemia in whom right heart failure developed from leukemic infiltration of the heart with right ventricular outflow tract obstruction is described. Two-dimensional echocardiography helped guide successful treatment of this complication with radiation and chemotherapy.

Echocardiography↗
PubMed1986

A phase II trial of cisplatin and methylglyoxal bis-guanylhydrazone (MGBG) in recurrent squamous cell carcinoma of the head and neck.

Thirty-one patients with unresectable squamous cell carcinoma of the head and neck, 28 with local or distant recurrences following primary surgery and/or radiation and three with distant metastases at diagnosis, were treated with cisplatin and methylglyoxal bis-guanylhydrazone (MGBG). Cisplatin was given at 60 mg/m2 i.v. every 21 days X 3, followed by 80 mg/m2 every 28 days in responding patients. MGBG 500 mg/m2 i.v. was given weekly X 5, then every 14 days. Each dose of MGBG was to be escalated in the absence of toxicity, but in the majority of patients doses greater than 500 mg/m2 resulted in unacceptable toxicity. Gastrointestinal symptoms were the major side effects of this combined treatment. In 28 evaluable patients there were two complete remissions and nine partial remissions. This 39% response rate is not different from that reported with either drug alone. Combined cisplatin and MGBG as administered in this study had no apparent advantage compared to either agent alone in this group of patients.

Adult↗
PubMed1986

A comparison of randomized concurrent control groups with matched historical control groups: are historical controls valid?

The use of a historical control group is predicated on the assumption that survival and relapse-free survival in the historical control group closely approximate the survival and relapse-free survival in a randomized concurrent control group. This assumption has never been tested. This study compares survival and relapse-free survival in randomized control groups with historical control groups matched for disease, stage, and follow-up. Of the 43 matched control groups, 42% varied by more than 10 percentage points, 21% varied by more than 20 percentage points, and 5% varied by more than 30 percentage points. Of the 18 that varied by greater than 10 percentage points, 17 had superior survival or relapse-free survival in the randomized concurrent control group. This study indicates that the assumption that historical control groups may replace randomized concurrent control groups is not valid.

Humans↗
PubMed1985

Multimodality therapy for unresectable squamous cell carcinoma of the head and neck.

Eighteen patients with unresectable Stage III or IV squamous cell carcinoma of the head and neck were treated with induction therapy consisting of sequential methotrexate and 5-fluorouracil. This was followed by full course radiation therapy and radical neck dissection for those with residual neck disease. Those with local control were then treated with vinblastine, bleomycin, and cisplatin (VBP). Although 79% of patients achieved a partial or complete response to chemotherapy, only 50% of patients achieved local control. Marked mucositis limited the dose and schedule of radiation therapy. The methotrexate and 5-fluorouracil combination appears to be too toxic for multimodality therapy of advanced head and neck cancer.

Adult↗