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Biomedical subjects

D Cavanagh

Publications and source records attributed to D Cavanagh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Avian encephalomyelitis virus is a picornavirus and is most closely related to hepatitis A virus.

The complete RNA genome of avian encephalomyelitis virus (AEV) has been molecularly cloned and sequenced. This revealed AEV to be a member of the Picornaviridae and consequently it is the first avian picornavirus for which the genome has been sequenced. Excluding the poly(A) tail the genome comprises 7032 nucleotides, which is shorter than that of any mammalian picornavirus sequenced to date. An open reading frame commencing at nucleotide 495 and terminating at position 6896 (6402 nucleotides) potentially encodes a polyprotein of 2134 amino acids. The polyprotein sequence has 39% overall amino acid identity with hepatitis A virus (HAV; genus Hepatovirus), compared to 19 to 21% for viruses from the other five picornavirus genera. Eleven cleavage products were predicted. The highest identity (49%) with HAV was in the P1 region, encoding the capsid proteins. The 5' and 3' untranslated regions (UTRs) comprise 494 and 136 nucleotides, respectively. The 5' UTR is the shortest of any picornavirus sequenced to date and, unlike HAV, it does not contain a long polypyrimidine tract.

Amino Acid Sequence↗
PubMed1999

Adenocarcinoma of the Endometrium: An Institutional Review.

BACKGROUND: Many oncologists regard endometrial cancer as a relatively benign and easily treatable gynecologic tumor. Inadequate care can result in poor outcomes. METHODS: The authors review the epidemiology and pathology of the disease, and they compare disease characteristics and outcomes of FIGO staging with their own 11-year experience at a tertiary referral center. RESULTS: Patients referred to tertiary referral centers tend to present with more advanced stages of disease than those reported by FIGO, although the profile of histologic types is similar. CONCLUSIONS: Prevention and early detection of endometrial cancer can minimize the impact of this disease. Complete staging and tumor removal including extrafascial hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and selective paraaortic lymphadenectomy are the cornerstones of surgical therapy.

Journal Article↗
PubMed1998

Body mass predicts the survival of patients with new International Federation of Gynecology and Obstetrics Stage IB1 and IB2 cervical carcinoma treated with radical hysterectomy.

BACKGROUND: The authors evaluated the impact of body mass on survival and morbidity of patients with new International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 and IB2 cervical carcinoma managed with radical hysterectomy. METHODS: Two hundred twenty-nine patients with Stage IB1 or IB2 cervical carcinoma treated with radical hysterectomy were studied in a multivariate logistic regression analysis. The body mass index (BMI) and the ponderal index (PI) were used as measures of body mass and were analyzed as predictors of recurrence, survival, and complications in light of the new staging system. RESULTS: Twenty-seven of 229 patients died of recurrent disease. A low BMI or a high PI were predictive of poor survival. Tumor greatest dimension, lymph node involvement, BMI, and PI were all independent predictors of survival (P=0.0006). The only independent predictor of complications was para-aortic lymph node dissection (P=0.0026). CONCLUSIONS: Cervical carcinoma patients with a low body mass, as indicated by a low BMI or a high PI, were found to have poor survival after undergoing radical hysterectomy. Additional predictors of poor survival included lymph node metastases and increased tumor size. BMI and PI are more important predictors of survival than the new FIGO Stages IB1 and IB2. Body mass is not predictive of complications.

Adolescent↗
PubMed1998

Sequence elements involved in the rescue of IBV defective RNA CD-91.

Deletion mutagenesis has been used to identify essential regions for rescue of coronavirus defective RNAs (D-RNAs). Using this technique on a cloned IBV D-RNA CD-91, we have identified a region potentially important in its rescue. Comparing the sequence of D-RNAs rescued with those not rescued we have deduced that a 72 base region corresponding to base number 13,824 to 13,896 in the viral genome is required for rescue. This may be an IBV D-RNA packaging signal or a cis-acting element involved in replication. Further experiments and modification of our techniques will be required to differentiate between the two processes.

Animals↗
PubMed1998

Rescue of IBV D-RNA by heterologous helper virus strains.

Coronavirus defective RNA (D-RNA) vectors could be developed to deliver selected genes for the production of recombinant coronavirus vaccines. An IBV D-RNA, CD-61, derived from a naturally occurring IBV Beaudette D-RNA, CD-91, is being developed as a D-RNA vector for IBV. In order to use CD-61 as a vector it will require rescue by heterologous strains in addition to Beaudette. Rescue will be determined by recognition of replication and packaging signals within the D-RNA by the helper virus. The 5' and 3' UTRs are believed to contain sequences involved in replication and transcription. The 5' and 3' UTRs of six strains of IBV have been sequenced and experiments performed using six strains of helper virus for rescue of CD-61 to determine whether rescue correlates with sequence conservation within the 5' and 3' UTRs. Results indicate that all strains of helper virus rescued the D-RNA to varying degrees. Sequence comparisons show a high degree of sequence identity in the UTRs, but enough strain differences exist to be used as markers. The 5' and 3' UTRs of the D-RNAs rescued by the heterologous strains were also sequenced and leader switching between the helper virus and the Beaudette leader on the D-RNAs was observed.

3' Untranslated Regions↗
PubMed1998

Utilising a defective IBV RNA for heterologous gene expression with potential prophylactic application.

Based on the natural ability of coronaviruses to undergo homologous RNA recombination, we are working to produce infectious bronchitis virus (IBV) recombinants using RNA generated from recombinant fowlpox viruses (FPV). The aim is to replace the spike (S) gene of an existing IBV vaccine strain with the S gene of a heterologous strain. CD-61 is an IBV defective RNA (D-RNA) derived from a naturally occurring IBV D-RNA (CD-91). CD-61 D-RNA is being investigated as an RNA vector for the expression of heterologous genes. T7-derived RNA transcripts of CD-61 can be replicated and passaged in the presence of helper virus, following electroporation into IBV-infected cells. CD-61 cDNA was modified by the addition of the hepatitis delta virus ribozyme plus T7 terminator downstream of the 3'UTR. This allowed the synthesis of discreet RNA transcripts. The complete cassette was cloned into an FPV transfer vector (pEFL10) for generating recombinant fowlpox viruses. FPV/CD-61 recombinants will be assessed for D-RNA production in IBV-infected cells. The luciferase reporter gene sequence has been inserted into the modified CD-61, under the control of the IBV transcription associated sequence (TAS) from gene 5. Luciferase has been successfully expressed from CD-61 in helper virus-infected cells.

Animals↗
PubMed1998

Does IBV change slowly despite the capacity of the spike protein to vary greatly?

We have sequenced that part of the spike protein (S) gene which encodes the aminoterminal and most variable quarter (hypervariable region, HVR) of the S1 subunit of 28 isolates of the 793/B (also known as CR88 and 4/91) serotype of infectious bronchitis virus (IBV) and the whole of S1 for nine of them. The isolates were from France and Britain between the years 1985 (first isolation) and 1996. The maximum nucleotide and amino acid differences between the first isolate and the others were 4.1% and 7.6%, respectively, for the whole of S1 and 7.1% and 14.6%, respectively, in the HVR. Analysis within clearly recognisable subgroups suggested that even in the HVR the nucleotide mutation rate was only 0.3 to 0.6% per year. However, there was no evidence that mutations had become fixed in a progressive manner; this serotype did not appear to be evolving. Strains isolated several years apart could be more similar than those isolated in a given year. It is likely that the amino acid changes are largely at positions where amino acid differences are tolerated rather than as a consequence of immune pressure. Reasons for this conclusion are discussed.

Animals↗
PubMed1998

Endotoxin-induced atrial natriuretic factor release: in vivo and in vitro studies.

OBJECTIVE: We evaluated the effects of coliform endotoxin on the circulating levels of atrial natriuretic factor and renal function. To understand the direct effects of endotoxin in the release of atrial natriuretic factor by cardiac tissue, studies in isolated rat atria were performed. STUDY DESIGN: In vivo studies were used. Anesthetized dogs were studied, with one group receiving isotonic saline solution (n = 6) and the other group receiving 50 microg/kg of coliform endotoxin (n = 7) as a continuous infusion over a 4-hour period. Cardiovascular parameters, renal function, and circulating levels of atrial natriuretic factor were measured at specified time intervals. In another set of experiments with in vitro studies left atria from Sprague-Dawley rats were isolated and perfused. In the control group (n = 9) the standard Krebs perfusate was used. In the endotoxin group (n = 9) coliform endotoxin was added at a concentration of 250 microg/mL to the standard perfusate. Atrial pressure was used as an index of stretch, and atrial natriuretic factor was measured from the perfusate. RESULTS: Administration of endotoxin resulted in decreased blood pressure (P < .05) with a concomitant increase in heart rate. Renal artery flow, however, showed an increase (P < .05) initially followed by a return to its baseline value, with a sustained increase occurring in the saline solution control group. A significant (P < .05) and sustained increase in the circulating levels of atrial natriuretic factor after endotoxin infusion did not prevent the decrease in fractional sodium excretion (P < .05) and creatinine clearance despite an increase in the urinary output. Serum sodium, serum potassium, and osmolalities, however, remained relatively stable. The study pertaining to isolated atria showed that in the presence of low atrial pressures, addition of endotoxin had no significant effect on the release of atrial natriuretic factor. With the increase in atrial pressure atrial natriuretic factor release was significantly higher in the group directly exposed to endotoxin compared with the control group. CONCLUSIONS: These studies demonstrate that the slow infusion of coliform endotoxin results in increased circulating levels of atrial natriuretic factor. This increase is in part due to the direct effect of endotoxin on the heart as indicated by studies in isolated atria. Our data suggest that atrial natriuretic factor in endotoxemia acts in an integrative manner with other hormones on a variety of target organs to modulate cardiovascular function and fluid balance.

Animals↗
PubMed1998

The ectodomains but not the transmembrane domains of the fusion proteins of subtypes A and B avian pneumovirus are conserved to a similar extent as those of human respiratory syncytial virus.

The fusion glycoprotein (F(B)) gene of five strains of the B subtype of avian pneumovirus (APV; turkey rhinotracheitis virus) has been sequenced. The length of the F(B) protein was 538 amino acids, identical to that of the F protein of subtype A virus, with which it had 74% and 83% overall nucleotide and deduced amino acid identities, respectively. The F(B) and F(A) ectodomains had 90% amino acid identity, very similar to the 91% identity between the ectodomains of the F proteins of subtype A and B human respiratory syncytial virus (HRSV). As with HRSV, the F2 polypeptide was less conserved (83% identity) than F1 (94%). In contrast to the ectodomain, the transmembrane and cytoplasmic domains of the two APV subtypes were much less conserved (30% and 48% identity, respectively) than those of HRSV (92% and 87%, respectively). Comparisons within all the genera of the Paramyxoviridae (Pneumovirus, Morbillivirus, Paramyxovirus and Rubullavirus) show that low amino acid identity between F protein transmembrane domains is a feature of different species of virus rather than of strain differences. This may indicate that the two subtypes of APV have evolved in different geographical regions and/or different avian species. This is the first report of an F gene sequence from a subtype B APV.

Amino Acid Sequence↗
PubMed1998

Infections and reinfections with avian pneumovirus subtype A and B on Belgian turkey farms and relation to respiratory problems.

A longitudinal study was performed on six turkey farms in order to determine whether infections with avian pneumovirus (APV) occur and if they are related to outbreaks of respiratory problems in Belgium. Blood was taken at 1-3 week intervals of 20 identified animals during the fattening period. On five farms, the turkeys seroconverted against APV shortly after the appearance of respiratory problems. On two farms, where the animals had not been vaccinated against APV, attempts were made to isolate APV during the outbreaks. Two isolates were obtained: one of subtype A, the other of subtype B. These results indicate that the respiratory problems on five farms were related to an infection with APV. A second increase in APV antibody titres detected on four farms at the end of the fattening period, indicates that reinfections frequently occur. This is, to our knowledge, the first report on the isolation of an APV subtype A on the continent.

Animals↗
PubMed1997

Management of gynecologic oncology patients with a preoperative deep vein thrombosis.

Our experience with gynecologic oncology patients presenting preoperatively with a deep vein femoral thrombosis is reported. Over a 3-year period data were collected on all patients at the University of South Florida (USF) requiring surgery for a known or suspected gynecologic cancer and having a concomitant active femoral venous thrombosis. Twelve such patients were managed. Management was divided among three options: heparinization, preoperative inferior vena cava (IVC) filter, and intraoperative IVC ligation. For two patients a filter could not be placed preoperatively due to tumor compression of the IVC. Both underwent IVC ligation intraoperatively. One of the two died intraoperatively, possibly related to pulmonary embolism. One of eight with a preoperative IVC filter had obvious clot propagation postoperatively, managed with heparin. One of two managed with heparin only had severe bleeding and heparin-associated thrombocytopenia (HAT) preoperatively. Based on our experience and a review of the literature, we recommend therapeutic heparinization and a preoperatively placed IVC filter for most preoperative gynecologic oncology patients with femoral deep venous thrombosis.

Adult↗
PubMed1997

A pilot study utilizing intraoperative lymphoscintigraphy for identification of the sentinel lymph nodes in vulvar cancer.

OBJECTIVE: To identify sentinel lymph nodes using intraoperative lymphoscintigraphy. METHODS: Technetium-99-labeled sulfur colloid was injected at the site of primary vulvar carcinoma. An intraoperative gamma counter was used to identify one or more sentinel lymph nodes. RESULTS: Ten patients underwent bilateral inguinal and femoral lymphadenectomy. The clinical stages are as follows: T1 in 6, T2 in 2, and T3 in 2. A total of four groins (3 patients) were positive for metastases. In one patient only the sentinel node was positive for disease. In a second patient, two unilateral nodes were positive for disease and both were identified with the gamma counter as sentinel nodes. In the third patient, a single sentinel node was positive for malignancy in each groin. Multiple nonsentinel lymph nodes were positive in each groin in this patient. In no case was the sentinel node negative when other nonsentinel nodes were positive. CONCLUSION: Intraoperative lymphoscintigraphy quantitatively identifies one or more sentinel lymph nodes. Since sentinel lymph nodes can be localized transcutaneously, this technique may be useful for selective lymphadenectomy. Larger patient accrual is necessary to verify this technique.

Female↗
PubMed1997

Towards the routine application of nucleic acid technology for avian disease diagnosis.

The use of nucleic acid technology (polymerase chain reaction, probing, restriction fragment analysis and nucleotide sequencing) in the study of avian diseases has largely been confined to fundamental analysis and retrospective studies. More recently these approaches have been applied to diagnosis and what one might call real-time epidemiological studies on chickens and turkeys. At the heart of these approaches is the identification and characterisation of pathogens based on their genetic material, RNA or DNA. Among the objectives has been the detection of pathogens quickly combined with the simultaneous identification of serotype, subtype or genotype. Nucleic acid sequencing also gives a degree of characterisation unmatched by other approaches. In this paper we describe the use of nucleic acid technology for the diagnosis and epidemiology of infectious bronchitis virus, turkey rhinotracheitis virus (avian pneumovirus) and Newcastle disease virus.

Animals↗
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↗