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Biomedical subjects

D Cavanagh

Publications and source records attributed to D Cavanagh.

At least 181 records · Page 10Linked to original sources

Carcinoma in situ of the vulva: 24 years' experience in southwest Florida.

We retrospectively studied 125 patients treated for carcinoma in situ of the vulva from 1961 through 1984, with follow-up ranging from one to 24 years. Patients' ages ranged from 24 to 90 years, with a mean age of 53 years. Multifocal disease was more common in women under age 40. Pruritus was the most common complaint, but 60% of the patients were asymptomatic. Twenty-five patients (20%) had other associated malignancies: carcinoma in situ of the cervix in ten patients, invasive carcinoma of the cervix in six, multifocal carcinoma in situ involving vulva, vagina, and cervix in five, vaginal carcinoma in situ in two, and endometrial carcinoma in two. Sixty-five patients were treated primarily with wide excision, 45 with total vulvectomy, seven with "subtotal" vulvectomy, three with skinning vulvectomy, and three with vulvectomy and bilateral groin node dissection; two patients refused treatment. Fifteen patients had a recurrence--recurrent carcinoma in situ in ten, and invasive carcinoma of the vulva in five. Whether the patient had had total vulvectomy or a lesser procedure appeared to make no difference in the recurrence rate. Thus a well planned excision of vulvar carcinoma in situ appears to be the treatment of choice. All recurrences were in patients over age 40, so although the lesion is histopathologically identical in the younger patients, its biologic behavior seems to be more benign. Since it is possible, however, that invasive disease will ultimately develop in some of the younger patients, careful follow-up is still required.

Adult↗

Evolution of avian coronavirus IBV: sequence of the matrix glycoprotein gene and intergenic region of several serotypes.

We have sequenced 200 to 240 bases of the matrix (M) glycoprotein gene of 23 strains of infectious bronchitis virus (IBV) representing the A (D207), B (D3896), C (D3128), D (D212), Massachusetts (Mass), UK11 and UK12 serotypes. The bases examined code for the external, hydrophilic region and the first membrane-embedded hydrophobic region of M, both regions comprising approximately 20 amino acids. As predicted from protein Mr studies the A/D and B/C serotypes had two and one potential glycosylation sites respectively. This variation appeared to derive from a combination of base substitutions and deletions/insertions. The glycosylation sequence Asn-Cys-Thr was highly conserved. Overall, the exposed part of M exhibited a fourfold greater extent of amino acid variation than did the membrane-embedded sequence. The transcription-associated homology region sequence (CUUAACAA) in the 5' intergenic region was identical in all strains but there was considerable variation as to its location. The M gene of UK12 appeared to have evolved from a group A-like M gene by a two stage process involving a base substitution in the intergenic region which generated a new AUG translation start codon followed by deletion of the original AUG. Isolate UK11 closely resembled Mass strains in the intergenic region but was dissimilar from all strains in the protein coding region. The M sequences of serotypes B and C were identical and those of the A and D serotypes very similar. These results are discussed in relation to recent sequencing of part of the spike glycoprotein gene of some of these strains and the discovery of in vitro recombination of murine hepatitis coronavirus.

Amino Acid Sequence↗

Neurologic complications of pelvic intraarterial chemoembolization performed with collagen material and cisplatin.

In three patients neurologic complications developed after chemoembolization procedures were performed with cisplatin and a new collagen material. Three patients with dominant unilateral stage III cervical carcinoma were entered into an investigative protocol attempting to control regional disease and pain with chemoembolization. All three patients had previously undergone surgery, radiation therapy, and intraarterial chemoembolization or chemoinfusion. Each case was complicated by neurologic deficits. A collagen material was administered that acts at a precapillary level and reduces the likelihood of collateral flow. The size of the material enables it to embolize the small feeding vessels of the spinal cord and peripheral nerves. The patients in this study also had predisposing factors to neurologic sequelae including the previous therapy and the contributing neurotoxicity of cisplatin. The neurologic complications in these patients are not easily explained by knowledge of the neurovascular anatomy. Even with meticulous technique, intraarterial chemoembolization of the pelvis with cisplatin and collagen can be complicated by serious neurologic deficits.

Adult↗

Diagnosis and management of vulvar carcinoma.

With the steady increase in life expectancy, invasive cancer of the vulva is now becoming more prominent among gynecologic malignancies. Early, careful examinations and informed patients can aid in early diagnosis. Carcinoma in situ, verified by biopsy, is best treated with wide local excision. Invasive vulvar carcinoma should be treated with radical vulvectomy and bilateral groin node dissection. The major source of morbidity is wound breakdown. The use of modified incision techniques and sartorius muscle transplantation have significantly decreased these postoperative complications. The clinical staging system for vulvar carcinoma is approved by the International Federation of Gynecology and Obstetrics (FIGO). The disease usually spreads systematically from the vulva to superficial groin nodes, to deep groin nodes, and then to pelvic nodes. Survival rates of 84% for stage I disease can be achieved. Evidence of positive groin nodes indicates a poor prognosis. However, even patients with advanced disease can be surgically cured by radical surgery. Five of ten patients (50%) with stage IV disease were alive and free of disease at five years with exenterative surgery. Any patient who is a reasonable medical risk, with a vulvar lesion that is resectable, should be treated surgically. Otherwise, the patients not only die, but they die in abject misery.

Female↗

Dose-dependent effects of prostaglandin D2 on hemodynamics, renal function, and blood gas analyses.

Dose-response effects of prostaglandin D2 (0.125, 0.25, 0.5, and 0.75 micrograms/kg/min) infused intravenously in pentobarbital-anesthetized dogs were studied with particular reference to renal, pulmonary, and systemic effects. Another group receiving the vehicle alone served as controls. Prostaglandin D2 administration resulted in a significant dose-dependent increase in renal artery flow, urine output, creatinine clearance, plasma renin activity, sodium excretion, potassium excretion, and pulmonary artery pressure. A significant decrease occurred in renal resistance and arterial PO2. There were no appreciable changes in mean arterial pressure, heart rate, hematocrit, platelet count, arterial pH, and PCO2. In the vehicle control group, all other parameters remained relatively stable, except for some increase in the mean arterial pressure, plasma renin activity, and potassium excretion. The results of this study suggest that prostaglandin D2 administered intravenously at levels lower than those required to produce adverse pulmonary and systemic effects will improve the renal blood flow and function.

Animals↗

Value of computerized axial tomography in cervical cancer.

Results of preoperative abdominopelvic computerized axial tomography were compared with operative findings in 58 patients undergoing laparotomy for cervical cancer. Patients with stages IA, IB, IIA, IIB, IIIB, and recurrent carcinoma of the cervix were included. The abdominopelvic contents were divided into retroperitoneal, intraperitoneal-abdomen and intraperitoneal-pelvic compartments for purposes of evaluation. The overall sensitivity was 47.6% and the overall specificity was 96.4%. The highest sensitivity was associated with intraperitoneal-pelvic findings while the lowest sensitivity was associated with pelvic lymphadenopathy. The highest false positive results were associated with parametrial involvement. Computerized axial tomography is probably not cost effective in stage IB or IIA disease. It may be cost effective in stage IIB or greater as well as in recurrent cervical cancer. In the event a positive finding can be confirmed by needle aspiration and cytology, a staging procedure or exenteration attempt can be avoided.

Female↗

Role of needle biopsy in the investigation of gynecologic malignancy.

Three methods were used to investigate and evaluate patients with primary and persistent/recurrent pelvic malignancy in the gynecologic oncology services at two medical centers. The 22-gauge Chiba needle was utilized with fluoroscopic guidance to perform fine needle aspiration (FNA) of pelvic and paraaortic lymph nodes that appeared abnormal on lymphangiography (LAG). The Tru-cut needle was used to obtain tissue samples from beneath the surface epithelium of the cervix, vaginal vault and parametrium. A disposable, hand-held syringe and 20-gauge needle were used to aspirate supraclavicular and inguinal lymph nodes and cul-de-sac nodules. One hundred thirty-eight patients were evaluated, with positive results in 66 (47.8%). Surgical exploration was used to further investigate 16 negative results that did not correlate with LAG and/or clinical presentation. The sensitivity and predictive value of a negative result for the three methods was Chiba needle FNA/LAG, 62.1% and 65.6%; Tru-cut needle biopsy, 94.4% and 93.5%; and hand-held syringe and needle, 87.5% and 66.7%, respectively. All three techniques proved to be safe, uncomplicated and rapid methods of assessing gynecologic tumor spread. Positive results from these techniques can often replace surgical exploration, with a considerable savings in patient morbidity and hospitalization, and permit additional treatment to proceed without delay. Negative results still require surgical validation.

Biopsy, Needle↗

Major morbidity after pelvic exenteration: a seven-year experience.

Thirty-eight patients underwent pelvic exenteration at the University of South Florida during the last seven years. The majority of the operations were performed for recurrent carcinoma of the cervix, and the operative mortality was 5.3%. Twenty-one patients developed major morbidity in the postoperative period, and 11 with complications involving the gastrointestinal or urinary tract required reoperation. Multivariate logistic regression analysis demonstrated a correlation between the amount of pelvic radiation, type of pelvic floor, type of pelvic drain, amount of blood loss, race, and the occurrence of serious postoperative morbidity. Strategies to avoid serious postoperative morbidity are discussed.

Adult↗

Peritoneal cytology and invasive carcinoma of the cervix.

One hundred thirty-nine patients with invasive carcinoma of the cervix underwent laparotomy at the University of South Florida between February 1980 and November 1983. One hundred nineteen had laparotomy prior to treatment and 20 after treatment for recurrence or some other reason. One hundred twenty patients had negative peritoneal cytology, 8 had equivocal cytology and 11 had positive cytology. Positive peritoneal cytology was more common in higher-stage disease and was statistically significantly more common in patients with positive retroperitoneal lymph nodes (P less than 0.05). The rate of peritoneal cytologic positivity in patients with squamous carcinoma was the same as that for adenocarcinoma and adenosquamous carcinoma. Positive peritoneal cytology was associated with a very poor prognosis but was associated with other poor prognostic factors in all but 1 patient. Equivocal cytology did not seem to be of any particular significance. No patient in this series had an alteration in treatment planning based on peritoneal cytology. The utility and future of peritoneal cytology in invasive carcinoma of the cervix are discussed.

Actuarial Analysis↗

Coronavirus IBV: partial amino terminal sequencing of spike polypeptide S2 identifies the sequence Arg-Arg-Phe-Arg-Arg at the cleavage site of the spike precursor propolypeptide of IBV strains Beaudette and M41.

The spike protein of avian infectious bronchitis coronavirus comprises two glycopolypeptides S1 and S2 derived by cleavage of a proglycopolypeptide So, the nucleotide sequence of which has recently been determined for the Beaudette strain (Binns, M.M. et al., 1985, J. Gen. Virol. 66, 719-726). The order of the two glycopolypeptides within So is aminoterminus(N)-S1-S2-carboxyterminus(C). To locate the N-terminus of S2 we have performed partial amino acid sequencing on S2 from IBV-Beaudette labelled with [3H]serine and from the related strain labelled with [3H]valine, leucine and isoleucine. The residues identified and their positions relative to the N-terminus of S2 were: serine, 13; valine, 6, 12; leucine, none in the first 20 residues; isoleucine, 2, 19. These results identified the N-terminus of S2 of IBV-Beaudette as serine, 520 residues from the N-terminus of S1, excluding the signal sequence. Immediately to the N-terminal side of residue 520 So has the sequence Arg-Arg-Phe-Arg-Arg; similar basic connecting peptides are a feature of several other virus spike glycoproteins. It was deduced that for IBV-Beaudette S1 comprises 519 residues (Mr 57.0K) or 514 residues (56.2K) if the connecting peptide was to be removed by carboxypeptidase-like activity in vivo while S2 has 625 residues (69.2K). Nucleotide sequencing of the cleavage region of the So gene of IBV-M41 revealed the same connecting peptide as IBV-Beaudette and that the first 20 N-terminal residues of S2 of IBV-M41 were identical to those of the Beaudette strain. IBV-Beaudette grown in Vero cells had some uncleaved So; this was cleavable by 10 micrograms/ml of trypsin and of chymotrypsin. Partial N-terminal analysis of S1 from IBV-M41 identified leucine and valine residues at positions 2 and 9 respectively from the N-terminus. This confirms the identification, made by Binns et al. (1985), of the N-terminus of S1 and the end of the signal sequence of the IBV-Beaudette spike propolypeptide. N-terminal sequencing of [3H]leucine-labelled IBV-Beaudette membrane (M) polypeptide showed leucine residues at positions 8, 16 and 22 from the N-terminus; these results confirm the open reading frame identified by M.E.G. Boursnell et al. (1984, Virus Res. 1, 303-313) in the nucleotide sequence of M. The N-terminus of the nucleocapsid (N) polypeptide appeared to be blocked.

Amino Acid Sequence↗

Coronavirus IBV glycopolypeptides: locational studies using proteases and saponin, a membrane permeabilizer.

[35S]methionine-labelled avian infectious bronchitis virus (IBV) (strain 41) and its purified protein components and virions of IBV-Beaudette were incubated with 10 proteases. Several proteases hydrolysed all or some of the membrane glycopolypeptide (M; Mr 30K) and removed about 1.3K of peptide from the amino-(N-)-terminus plus both glycans, as determined by SDS-polyacrylamide gel electrophoresis. N-terminal analysis of [3H]isoleucine-labelled M after hydrolysis by bromelain revealed that the first nine residues had been removed. After the virions had been permeabilised with saponin, a further 2.5K decrease in molecular weight was produced and this was shown to be from the carboxy-(C-)terminus. When considered with the hydropathicity plot analysis of the amino acid sequence of M (Boursnell, M.E.G. et al., 1984, Virus Res. 1, 303-313) these results suggest that as few as 9-20 N-terminal amino acid residues may protrude at the outer membrane surface and that there is a highly protease sensitive sequence of an estimated 20-25 residues at the C-terminus of M exposed in the lumen of the virion. S2 but not S1 was cleaved to a major glycopolypeptide of approximately 71K by several proteases, and to 76K by trypsin. N-terminal sequencing of the 71K glycopolypeptide revealed that it had the same N-terminus as intact S2. After hydrolysis in the presence and absence of saponin it was concluded that S2 is very sensitive to hydrolysis near its carboxy terminus at residues close to the outer membrane surface.

Amino Acid Sequence↗

Coronavirus IBV: virus retaining spike glycopolypeptide S2 but not S1 is unable to induce virus-neutralizing or haemagglutination-inhibiting antibody, or induce chicken tracheal protection.

Avian infectious bronchitis coronavirus (IBV) inactivated by beta-propiolactone induced partial protection of the trachea in up to 40% of chickens following one intramuscular inoculation 4 to 6 weeks prior to challenge. Retention of an intact tracheal ciliated epithelium 4 days after challenge was the criterion of protection. There was no correlation between protection and serum titres of virus-neutralizing (VN) and haemagglutination-inhibiting (HI) antibody, which were maximal at about 4 weeks after inoculation. Virus from which the S1 but not the S2 (spike-anchoring) spike glycopolypeptide had been removed by urea did not induce protection or VN or HI antibody. Four intramuscular inoculations of monomeric S1 induced VN and HI antibody in two and four chickens respectively. These results indicate that VN and HI antibodies are induced primarily by S1, that intact spikes are a major requirement for the induction of protective immunity and that this property is probably associated with S1.

Animals↗

Coronavirus IBV: removal of spike glycopolypeptide S1 by urea abolishes infectivity and haemagglutination but not attachment to cells.

Urea has been used to remove the S1 spike glycopolypeptide from avian infectious bronchitis virus (IBV) strains M41 and Beaudette, without removing the S2 spike-anchoring glycopolypeptide. Reduction of the pH to 2.9 did not cause release of S1 although some S1 was released spontaneously from IBV Beaudette at pH 7.4. Virus that lacked S1 was no longer infectious or able to cause haemagglutination (HA). However, radiolabelled IBV that lacked S1 attached to erythrocytes and chick kidney cells to the same or similar extent as did intact virus. Treatment of IBV with a phospholipase C preparation, required to make IBV cause HA, did not increase binding of IBV to erythrocytes. The results indicate that while the attachment to cells of virus that lacks S1 is qualitatively different from that of intact virus, the decline in infectivity is the consequence of the loss of some other spike function.

Animals↗

Changing trends in the surgical treatment of invasive carcinoma of the vulva.

Twenty-nine years experience with 346 patients with invasive carcinoma of the vulva is presented. More than 90 per cent had squamous carcinoma. The primary mode of treatment was surgical. Two hundred and ninety-six patients were treated primarily with surgical treatment, 120 underwent radical vulvectomy and bilateral groin and pelvic lymphadenectomy, 133 had radical vulvectomy with bilateral groin dissection and 390 receiving nonradical procedures. Thirteen patients had radical operations plus pelvic exenteration for advanced disease. There were no intraoperative deaths, but 16 (5.4 per cent) died within 28 days of the operation. The uncorrected over-all five year survival rate was 66 per cent. In the presence of negative nodes, it was 83 per cent and with positive nodes, it was 38 per cent. Fifty per cent of those treated with exenteration are alive and disease-free at five years or more. Since one-third of the patients presented with advanced disease (Stages III and IV), earlier diagnosis and prompt referral must be encouraged to improve surgical results.

Adult↗

Factors affecting the incidence of infectious morbidity after radical hysterectomy.

A double-blind, placebo-controlled trial was performed to assess the value of cefoxitin for prophylaxis against postoperative infection following radical hysterectomy. Infectious morbidity was observed in 35% of 43 patients in the control group and 23% of 31 in the cefoxitin group. In seven control patients (16%) and one patient (3%) in the cefoxitin group the infections were related to the surgical site (p = 0.07). These differences did not achieve statistical significance. Examination of the data revealed a number of other factors, including operating time, patient weight, blood loss, and blood replacement, that were significantly related to the incidence of infectious morbidity. Comparison of the results of the present study with those in the literature indicates that a careful examination of the circumstances prevailing in any particular institution is necessary before a decision is made on strategies to combat infectious morbidity after radical hysterectomy.

Adult↗

Pregnancy-induced hypertension: development of a model in the pregnant primate (Papio anubis).

Experiments were performed on two groups of pregnant baboons. In the experimental group, the subrenal aortic blood flow was reduced by 58% of its original value at 100 days of gestational age. In the control group, the blood flow was measured but not restricted. In the experimental group fetal death occurred in three of 12 animals following the use of a single left-flank incision to approach both the renal artery and the abdominal aorta. In the control group, pregnancies in eight of nine animals went successfully to 165 days. In the experimental group the development of hypertension, a decrease in plasma renin activity, an increase in renal resistance, an increase in serum uric acid, and the development of glomerular changes consistent with those seen in human pregnancy-induced hypertension were noted. These studies demonstrate that pregnancy-induced hypertension can be produced experimentally in a pregnant baboon, and this model should prove useful in expediting studies on the pathophysiologic features and treatment of this condition.

Animals↗