PubMed Health⌕ Search

Biomedical subjects

D Cavanagh

Publications and source records attributed to D Cavanagh.

At least 37 records · Page 2Linked to original sources
PubMed1996

A single institution experience with weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease.

The purpose of this study is to report our experience with weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. Treatment was begun at a dose of 40 mg/m2 and escalated weekly by 5-10 mg/m2, depending upon response and tolerance, to a maximum dose of 60 mg/m2. Remission was induced with weekly intramuscular methotrexate alone in 12 (60%) of 20 patients in 2-12 (median 8) weeks. The remaining 7 patients had a complete response to alternate chemotherapy. There were no major toxicities. Although the results of the present study are less favorable in terms of response, the overall published results using weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease indicate that it is comparable in efficacy to other first-line treatments while having the advantages of convenience, low cost, and low toxicity.

Adolescent↗
PubMed1996

Chemotherapy plus sequential hormonal therapy for advanced and recurrent endometrial carcinoma: a phase II study.

We evaluated the therapeutic value of sequential cyclical hormonal therapy (megestrol acetate, and tamoxifen citrate) plus single-agent chemotherapy (carboplatin) in the outpatient management of advanced or recurrent endometrial cancer. Carboplatin (300 mg/m2) was administered every 4 weeks for six courses or until disease progression. In addition, patients alternated megestrol acetate (80 mg orally twice daily) with tamoxifen citrate (20 mg orally twice daily) every 3 weeks. Thirteen of 18 (72.2%) patients were considered evaluable. Four patients (30.8%) had a complete response, six (46.2%) had a partial response, one (7.7%) had stable disease, and two patients (15.4%) progressed. Six of seven patients with vaginal disease responded. The median progression-free interval was 14 months for complete responders. Two patients (15.4%) are alive with no evidence of disease at 41 and 59 months. Seven of 13 patients experienced a hematologic toxicity (six grade 2, one grade 3); all resolved within 2 weeks. Dose reduction of carboplatin to 200 mg/m2 was required in one patient. No other toxicities were encountered. The median survival for all patients is 11 months, and is 33 months for complete responders. We conclude that a regimen of carboplatin plus sequential hormonal therapy shows promise in this pilot study for the treatment of advanced or recurrent endometrial cancer.

Adult↗
PubMed1996

Radical hysterectomy for stage IB1 vs IB2 carcinoma of the cervix: does the new staging system predict morbidity and survival?

Two hundred twenty-nine patients with Stage IB cervical cancer treated with radical hysterectomy were assigned to the new FIGO substages IB1 (n = 181) and IB2 (n = 48) based on clinical tumor diameter. Our purpose was to determine the impact of the new staging system for IB1 and IB2 cervical cancer on nodal status and survival. Additionally, we analyzed the morbidity of radical hysterectomy in light of the new staging system. The complications were similar between the two groups. Para-aortic lymphadenectomy was the only independent predictor of complications (P = 0.00026). Stage IB2 patients did have a significantly worse 5-year survival (72.8%) when compared with IB1 (90.0%) (P = 0.0265). Multivariate stepwise logistical regression analysis indicated that the new staging system did not have an independent impact on survival. Stage acts through nodal status in its impact on survival. Positive lymph nodes, tumor diameter, and Ponderal Index are all independent predictors of survival (P = 0.0001). Patients with Stage IB2 carcinoma of the cervix undergoing radical hysterectomy showed no significant increase in morbidity when compared with patients with Stage IB1 disease treated with the same procedure.

Analysis of Variance↗
PubMed1996

Massive pelvic hemorrhage during gynecologic cancer surgery: "pack and go back".

Over a 13-year period, intraabdominal packing has been used to control massive hemorrhage during surgery for gynecologic malignancy in six patients. Five patients had undergone total pelvic exenteration and one total abdominal hysterectomy with bilateral salpingo-oophorectomy for endometrial cancer. Massive hemorrhage was defined as infusion of more than 10 units of blood and replacement of more than one total blood volume. Tamponade was performed using continuous Kerlex rolls (Kendall Co., Boston, MA) in a bowel bag with directed pressure over the hemorrhaging site with abdominal closure. The packs were removed in 48 to 72 hr in the operating room, transabdominally in five patients and transvaginally in one. One postoperative death occurred within 8 hr of surgery. The packing was ultimately successful in the five remaining patients. In five of six patients, tumors were removed before the packing, whereas in one, the tumor was removed concurrently with the pack. In one patient, immediate repacking was required after pack removal, with ultimate hemostasis. Morbidity included "empty pelvis syndrome" in four patients, neuropathy in three (obturator in 1, sciatic in 2), and small bowel obstruction in one. In patients with severe intraoperative hemorrhage, intraabdominal packing has been successful as a mode of treatment.

Adult↗
PubMed1996

Sequence of the nucleocapsid protein gene of subgroup A and B avian pneumoviruses.

The nucleocapsid protein (N) gene of two subgroup A and one subgroup B strains of avian pneumovirus has been cloned and sequenced. The gene of all three isolates comprised 1197 nucleotides (nt), which formed a single major open reading frame, potentially encoding a protein of 391 amino acid residues. The N gene of the two subgroup A isolates differed by only 1 nt but differed by 282 (24%) nt and 35 (11%) amino acids from the B isolate. The predicted protein was identical in length to that of human, bovine and ovine respiratory syncytial viruses, the amino acid identity being approximately 41% overall but with some regions of identity > 90%.

Amino Acid Sequence↗
PubMed1996

Radical hysterectomy for stage IB cervical cancer: recurrence interval as a predictor of survival.

Two hundred patients with stage IB carcinoma of the cervix were treated with radical hysterectomy. We evaluated the impact of recurrence interval on survival and determined its relationship to other prognostic factors. Thirty-one patients (15.5%) had recurrence, with a median follow-up of 2.8 years (range, 1 to 5 years). Multivariate analysis, using the Cox proportional hazard regression model, showed the impact of recurrence interval on survival and its relationship to other prognostic factors. Patients were 19 times more likely to die during follow-up if recurrence occurred shortly after the operation. However, the risk of death from recurrence decreased exponentially as recurrence interval increased, by a multiple of 0.93 m where m is recurrence interval in months. We conclude that in patients with stage IB carcinoma of the cervix treated initially with radical hysterectomy, the shorter the recurrence period after operation, the greater the likelihood the patient would die during 5-year follow-up. This information may help clinicians determine a patient's prognosis after confirmed recurrence.

Aged↗
PubMed1996

The clinical significance of calculated versus measured creatinine clearance in patients with gynecologic malignancy.

Measurement of creatinine clearance remains in convenient because of the need for 24-hour urine collection. Our study compared creatinine clearance calculated from serum creatinine (CC alpha) to measured creatinine clearance (MC alpha) using an unsupervised 8-hour urine collection at home. Forty-two women admitted to our gynecologic oncology service participated in this study. Twenty-six of these patients had cancer originating from the ovaries, 8 from the uterus, 7 from the cervix, and 1 from the fallopian tube. There were adequate data for 61 collections. MC alpha using unsupervised 8-hour urine collection at home correlated well with CC alpha. This calculated value may be sufficient to be used as a guide in evaluating renal function in patients with gynecologic malignancy. However, if it becomes necessary to measure creatinine clearance, our data suggest that an 8-hour collection may be used.

Age Factors↗
PubMed1996

Nucleotide sequence of the gene encoding the viral polymerase of avian pneumovirus.

We report here the nucleotide sequence of the L gene of avian pneumovirus (APV). This is the second pneumovirus L gene and the second avian paramyxovirus L gene, following that of Newcastle disease virus, to be sequenced. The APV L gene is 6099 nucleotides long and encodes a single large ORF of 2004 amino acids. This makes the APV L protein the smallest to be described for any nonsegmented, negative-strand RNA virus. The protein contains six linear non-contiguous domains, a putative ATP-binding site and four polymerase motifs previously described for the L proteins of negative-strand RNA viruses. Phylogenetic analysis of domain III of 14 different L proteins suggests the pneumoviruses to be as distant in evolutionary terms from the other members of the Paramyxoviridae as are the Filoviridae.

Amino Acid Sequence↗
PubMed1996

Expression of bacteriophage T7 RNA polymerase in avian and mammalian cells by a recombinant fowlpox virus.

The bacteriophage T7 RNA polymerase gene was integrated into the fowlpox virus genome under the control of the vaccinia virus early/late promoter, P7.5. The recombinant fowlpox virus, fpEFLT7pol, stably expressed T7 RNA polymerase in avian and mammalian cells, allowing transient expression of transfected genes under the control of the T7 promoter. The recombinant fowlpox virus expressing T7 RNA polymerase offers an alternative to the widely used vaccinia virus vTF7-3, or the recently developed modified vaccinia virus Ankara (MVA) T7 RNA polymerase recombinant, a highly attenuated strain with restricted host-range. Recombinant fowlpox viruses have the advantage that as no infectious virus are produced from mammalian cells they do not have to be used under stringent microbiological safety conditions.

Animals↗
PubMed1996

Replication and packaging of coronavirus infectious bronchitis virus defective RNAs lacking a long open reading frame.

The construction of a full-length clone of the avian coronavirus infectious bronchitis virus (IBV) defective RNA (D-RNA), CD-91 (9,080 nucleotides [Z. Penzes et al., Virology 203:286-293]), downstream of the bacteriophage T7 promoter is described. Electroporation of in vitro T7-transcribed CD-91 RNA into IBV helper virus-infected primary chick kidney cells resulted in the production of CD-91 RNA as a replicating D-RNA in subsequent passages. Three CD-91 deletion mutants were constructed--CD-44, CD-58, and CD-61--in which 4,639, 3,236, and 2,953 nucleotides, respectively, were removed from CD-91, resulting in the truncation of the CD-91 long open reading frame (ORF) from 6,465 to 1,311, 1,263, or 2,997 nucleotides in CD-44, CD-58, or CD-61, respectively. Electroporation of in vitro T7-transcribed RNA from the three constructs into IBV helper virus-infected cells resulted in the replication and packaging of CD-58 and CD-61 but not CD-44 RNA. The ORF of CD-61 was further truncated by the insertion of stop codons into the CD-61 sequence by PCR mutagenesis, resulting in constructs CD-61T11 (ORF: nucleotides 996 to 1,058, encoding 20 amino acids), CD-61T22 (ORF: nucleotides 996 to 2,294, encoding 432 amino acids), and CD-61T24 (ORF: nucleotides 996 to 2,450, encoding 484 amino acids), all of which were replicated and packaged to the same levels as observed for either CD-61 or CD-91. Analysis of the D-RNAs showed that the CD-91- or CD-61-specific long ORFs had not been restored. Our data indicate that IBV D-RNAs based on the natural D-RNA, CD-91, do not require a long ORF for efficient replication. In addition, a 1.4-kb sequence, corresponding to IBV sequence at the 5' end of the 1b gene, may be involved in the packaging of IBV D-RNAs or form part of a cis-acting replication element.

Animals↗
PubMed1996

Characterization in vitro of an autocatalytic processing activity associated with the predicted 3C-like proteinase domain of the coronavirus avian infectious bronchitis virus.

A region of the infectious bronchitis virus (IBV) genome between nucleotide positions 8693 and 10927 which encodes the predicted 3C-like proteinase (3CLP) domain and several potential cleavage sites has been clones into a T7 transcription vector. In vitro translation of synthetic transcripts generated from this plasmid was not accompanied by detectable processing activity of the nascent polypeptide unless the translation was carried out in the presence of microsomal membrane preparations. The processed products so obtained closely resembled in size those expected from cleavage at predicted glutamine-serine (Q/S) dipeptides and included a protein with a size of 35 kDa (p35) that corresponds to the predicted size of 3CLP. Efficient processing was dependent on the presence of membranes during translation; processing was found to occur when microsomes were added posttranslationally, but only after extended periods of incubation. C-terminal deletion analysis of the encoded polyprotein fragment revealed that cleavage activity was dependent on the presence of most but not all of the downstream and adjacent hydrophobic region MP2. Dysfunctional mutagenesis of the putative active-site cysteine residue of 3CLP to either serine or alanine resulted in polypeptides that were impaired for processing, while mutagenesis at the predicted Q/S release sites implicated them in the release of the p35 protein. Processed products of the wild-type protein were active in trans cleavage assays, which were used to demonstrate that the IBV 3CLP is sensitive to inhibition by both serine and cysteine protease class-specific inhibitors. These data reveal the identity of the IBV 3C-like proteinase, which exhibits characteristics in common with the 3C proteinases of picornaviruses.

Animals↗
PubMed1996

Urokinase plasminogen activator in ovarian cancer.

Invasion and metastasis require the destruction of the extracellular matrix and basement membranes to facilitate growth or migration of tumor cells into vascular and lymphatic spaces. These processes are mediated by proteolytic enzymes. Malignant cells produce urokinase which is a protease known to enhance the invasiveness of many tumor cells. The relationship between urokinase and various prognostic factors was investigated in 16 patients with epithelial ovarian cancer. Tissue concentrations of urokinase were measured in tumor cytosols using enzyme-linked immunoassays. Urokinase levels were lower in ovarian tumors of low malignant potential (median 9.5, range 3.5-18.3 pg/mg protein, n = 4) than invasive cancers (median 44.6, range 16.1-210.6 pg/mg protein, n = 12), p < 0.01. In the invasive carcinomas urokinase levels did not vary significantly with tumor stage or cell type. Grade 3 tumors had higher levels of urokinase (median 120.4, range 21.4-397.1 pg/mg protein, n = 6) than grade 1 and 2 tumors (median 29.2, range 16.1-51.8 pg/mg protein, n = 6), p < 0.05. Urokinase levels were higher in recurrent (median 120.4, range 51.8-210.6 pg/mg protein, n = 4) than in primary (median 29.2, range 16.1-97.1 pg/mg protein, n = 8) tumors, p < 0.05. These results support the hypothesis that urokinase plays a role in invasion and metastasis of ovarian epithelial cancers and suggest that tissue levels of urokinase may have prognostic value.

Epithelium↗
PubMed1995

Experimental evidence of recombination in coronavirus infectious bronchitis virus.

Embryonated eggs were coinfected with two strains of the coronavirus avian infectious bronchitis virus (IBV), IBV-Beaudette and IBV-M41, to investigate whether recombination between the two strains would occur. Virions were isolated from the allantoic fluid of the coinfected eggs and putative hybrid RNAs were detected by polymerase chain reaction (PCR), using strain-specific oligonucleotides. PCR products, of the expected sizes, were obtained as predicted from potential recombination events between the nucleoprotein (N) gene and the 3'-untranslated region of the two IBV genomes. Sequencing confirmed that they corresponded to hybrid RNAs. Virus produced as a result of the mixed infection was treated with an M41-specific neutralizing monoclonal antibody and passaged in Vero cells, in which IBV-Beaudette, but not IBV-M41, replicated. Hybrid RNA was still detectable after three serial passages. Since no IBV-M41 was detectable this confirmed that infectious recombinant genomes had been produced in the embryonated eggs. These findings not only support the circumstantial evidence, from sequencing studies of IBV field strains, that recombination occurs during replication of IBV and contributes to the diversity of IBV, but also show that coronavirus RNA recombination is not limited to mouse hepatitis virus.

Animals↗
PubMed1995

A management scheme for postoperative groin lymphocysts.

During 1993, four persistent groin lymphocysts were diagnosed following inguinal lymphadenectomy for the management of gynecologic cancer. All four were successfully managed by a scheme involving active drainage combined with compression. Patient details and specifics of the suggested management scheme are outlined in the text.

Aged↗
PubMed1995

Interleukin-12-mediated tumoricidal activity of patient lymphocytes in an autologous in vitro ovarian cancer assay system.

This study was designed to examine if interleukin-12 (IL-12) can induce cytolytic function of lymphocytes from ovarian cancer patients against either an ovarian cancer cell line or their own autologous tumor cells. Lymphocytes were obtained from the peripheral blood or ascites of ovarian cancer patients and activated with IL-12 alone or concomitantly with interleukin 2 (IL-2) for 2 to 3 days. Activation of lymphocytes and assessment of tumoricidal function by a chromium release assay were performed directly in a standard control medium (RPMI 1640 containing 2 mM glutamine, 100 micrograms/ml streptomycin, 100 units penicillin, 5% heat-inactivated human AB serum, and 5 mM 4-(2-hydroxyethyl)-1-piperazinesulfonic acid) and in 50% ascitic fluid (50% by volume filter-sterilized ascites with 50% of the above-mentioned control medium). Target cells were added directly into the medium in which the lymphocytes were activated in order to more closely mimic in vivo conditions. Lymphocytes, activated by IL-12 in 50% ascitic fluid, were able to lyse autologous tumor cells in 3 of 6 assays and were able to lyse SKOV3 cells (an ovarian cancer cell line) in 5 of 7 assays. The results were not significantly different in the control medium. When both IL-2 and IL-12 were used to activate lymphocytes in 50% ascitic fluid, significant cytotoxicity was generated in 6 of 6 autologous assays and in all 7 patient assays using SKOV3 as a target (P < 0.05). Synergy between the two cytokines was seen in all 13 patient assays in ascitic medium compared to only 5 of 13 assays in control medium. Additionally, when lymphocytes were stimulated with both IL-2 and IL-12, significantly greater cytotoxicity was seen in the ascitic fluid medium compared to the control medium in 13 of 14 assays (P < 0.05). No significant tumoricidal activity was seen by lymphocytes maintained in either medium without the addition of IL-2 or IL-12. Ascitic fluid consistently potentiates the synergy between IL-2 and IL-12 in generating cytotoxicity against ovarian cancer cells but does not increase cytotoxicity induced by IL-12 alone. IL-12 by itself activates tumoricidal activity of lymphocytes in ascitic fluid; however, the addition of IL-2 increases the degree and consistency of this effect. These data support the possibility that IL-12 may warrant further investigation as a potential therapeutic agent in the treatment of advanced ovarian cancer.

Ascitic Fluid↗