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Biomedical subjects

W Barnes

Publications and source records attributed to W Barnes.

At least 19 recordsLinked to original sources

Radiotherapy of malignant subdiaphragmatic implants in advanced ovarian carcinoma: a new technique.

We report the development of a new technique using remote afterloading intraoperative radiation therapy to deliver a tumoricidal dose to diaphragmatic tumor implants. A multi-positional lucite applicator was designed based on anatomic studies of the diaphragmatic surface to accommodate a high dose rate iridium source in a series of needles placed 1.5 cm apart. The applicator curvature can vary from planar to full accommodation of the diaphragmatic surface with a constant source to surface distance of 0.5 cm. The applicator has been piloted in three patients with ovarian carcinoma with residual subdiaphragmatic disease found at second look laparotomy, to deliver a dose of 1,500 to 2,000 cGy at 0.5 cm. Tolerance of the diaphragm and hepatic surface has been excellent. There were no postoperative complications and no deterioration in liver function studies. The additional postoperative external beam irradiation directed with the aid of surgically placed clips and gated to respiratory movements permits achievement of a tumoricidal dose while limiting the treated volume and related toxicities.

Brachytherapy

Manometric characterization of rectal dysfunction following radical hysterectomy.

Bladder dysfunction thought to be due to partial denervation has been described following radical hysterectomy. Some patients experience acute and chronic rectal dysfunction characterized by difficulty with defecation and loss of defecatory urge. To define this abnormality, anorectal pressure profiles were examined in 15 patients with Stage I carcinoma of the cervix before and after radical hysterectomy. Profiles were done using standard anorectal manometry with a water-infused system. In all patients preoperative manometric profiles were normal; postoperative studies were abnormal in all patients. Features seen include altered relaxation of the internal sphincter, increased distension needed to trigger relaxation, and decreased rectal sensation; external sphincters and resting internal sphincters were unchanged. Postoperatively, 12 patients reported problems with rectal function. A physiologic defect is definable in patients undergoing radical hysterectomy; this suggests disruption of the spinal reflex arcs controlling rectal emptying. These physiologic abnormalities correlate with the clinical symptomatology experienced by some patients. Continuing definition and evaluation of management options in this situation should be useful in developing effective therapy for rectal dysfunction following radical hysterectomy.

Defecation

Reverse hysterocolposigmoidectomy (RHCS) for resection of panpelvic tumors.

Lateral retroperitoneal approaches to abdominopelvic masses are commonly employed; the reverse hysterocolposigmoidectomy (RCHS) in addition utilizes transabdominal entry of the vaginal and rectovaginal spaces to provide medial access to the uterosacral and cardinal ligaments as well expose a tumor-free segment of the rectosigmoid for en bloc resection of panpelvic tumors. Thirty-one patients underwent reverse hysterocolpectomy for extensive, symptomatic pelvic malignancies. All patients had complete resection of pelvic tumor, and there were no perioperative deaths. Sigmoid resection was required in 25 patients with 22 primary reanastomosis and 3 end colostomies performed. In 6 patients, vaginal entry facilitated tumor resection while sparing the rectosigmoid. Average operative blood loss was 2677 cc. Early postoperative morbidity (1-30 days) occurred in 13 patients; febrile morbidity (6 patients) was the common complication. Late morbidity (1-6 months) was seen in 10 patients, including 1 fatal pulmonary embolism at 5 months. Subsequent therapy was tolerated well. Mean survival/follow-up is 15.7 months (range, 1 to 49 months). Seventeen patients are alive, seven patients without evidence of disease (average 13.4 months), and ten patients are alive with disease (average follow-up, 28.3 months). Thirteen patients are dead of disease or complication (average survival, 13.7 months). We conclude that RHCS facilitates resection of extensive pelvic tumors with acceptable morbidity.

Adult

Oral contraceptive use, human papillomavirus infection, and risk of early cytological abnormalities of the cervix.

Oral contraceptive (OC) use was examined as a risk factor for cytological abnormalities of the cervix among 1964 women receiving Papanicolaou smears at three hospitals in the Washington, D.C., area. A single pathologist classified cytological results from all women as normal (n = 1423), atypia (n = 314), low grade squamous intraepithelial lesion (SIL; n = 208), or high grade SIL (n = 19). Women in each of the three abnormal groups were compared to women with normal cytological diagnoses. A subset of 579 patients, including most of the women with low or high grade SIL and a matched group of controls, was tested for human papillomavirus (HPV) by type-specific Southern blot hybridization to examine the effects of OC use while taking into account the effects of HPV infection. OC use was found to be unrelated to risk of atypia or low grade SIL but was associated with an elevated risk of high grade SIL that increased with longer duration of use (relative risk = 4.6, 95% confidence interval = 1.1-18.1 for greater than or equal to 5 years of use). HPV infection was associated, as expected, with risk of low and high grade SIL but not with atypia. Taking the HPV results into consideration did not alter the OC findings. There was no evidence that OC use synergistically increased the risk of cervical neoplasia among HPV-infected women, although small numbers prevented a reliable evaluation for high grade SIL. OC use did appear to increase the detection of HPV types 16/18, but the etiological importance of this finding is unclear.

Adult

Human cervical and foreskin epithelial cells immortalized by human papillomavirus DNAs exhibit dysplastic differentiation in vivo.

Human papillomavirus (HPV) DNAs are detected in approximately 90% of anogenital carcinomas. To assess directly the effect of HPV on squamous differentiation, normal human cervical and foreskin epithelial cells and cells immortalized by recombinant HPV DNAs were transplanted beneath a skin-muscle flap in athymic mice. Xenografts containing normal cells formed well-differentiated stratified squamous epithelia 2 to 3 weeks after transplantation, but cell lines immortalized by four HPV types (HPV16, HPV18, HPV31, and HPV33) detected in anogenital cancer exhibited dysplastic morphology and molecular alterations in gene expression characteristic of intraepithelial neoplasia. Morphological alterations were accompanied by delayed commitment to terminal differentiation, alterations in the pattern of involucrin expression, and reductions in levels of involucrin and keratin 1 RNAs. HPV18-immortalized cells developed dysplastic changes more rapidly than cells immortalized by HPV16 DNA. These results show that human genital epithelial cells immortalized by HPV DNAs detected in genital cancers undergo dysplastic differentiation in vivo.

Animals

Expression of the pregnancy-specific beta 1-glycoprotein genes in human testis.

Northern blot analysis with placental pregnancy-specific beta 1-glycoprotein (SP1) cDNA probe showed the presence of SP1 mRNAs in human testis. Presence of translational products of the mRNAs was demonstrated by Western blot analysis with anti-human SP1 antibodies albeit difference in mobilities between the testis and placental proteins was apparent. Screening of human testis cDNA library with placental SP1 probe yielded 4 groups of positive clones. Two groups were identical to human placental SP1 cDNAs previously reported. The other 2 groups consisted of cDNA of incompletely processed mRNAs. These 2 groups were present in high abundance. Sequence analysis suggested that the cDNAs were products of different genes.

Amino Acid Sequence

Rapid dysplastic transformation of human genital cells by human papillomavirus type 18.

This study delineates differences in biologic activity between human papillomavirus (HPV) types 16 and 18. Human cervical and foreskin epithelial cells were cultured and transfected with recombinant HPV-16 and -18 DNA, resulting in immortalized cell lines. Normal epithelial cells as well as HPV-16 and -18 immortalized cells of both early passages (less than 40 population doublings) and late passages (greater than 180 population doublings) were transplanted in athymic mice. Normal squamous cells formed well-stratified epithelium, while HPV immortalized cells developed either normal-appearing epithelium or typical dysplastic changes. Dysplastic changes were seen in none of the 13 grafts with early-passage HPV-16 cell lines, while 9 of 14 grafts with early-passage HPV-18 cell lines developed dysplasias (P less than 0.0004). These results support previous clinical observations suggesting that HPV-18 may be associated with a more aggressive and rapidly progressive form of cervical neoplasia.

Cell Transformation, Viral

Clindamycin effect on glycocalyx production in experimental viridans streptococcal endocarditis.

Abundant glycocalyx production by viridans streptococci in the rabbit model of endocarditis has been associated with delayed antimicrobial sterilization. Enzymatic digestion of the glycocalyx with dextranase enhances antibiotic activity. The effect of clindamycin (30 mg/kg, subcutaneous, three times daily) was studied in rabbits with experimental aortic valve endocarditis caused by high glycocalyx-producing viridans streptococci. Animals receiving clindamycin had smaller vegetations that were sterilized more quickly than did controls or animals receiving penicillin or dextranase alone (P less than .001). Penicillin plus dextranase treatment allowed greater bacterial killing than penicillin alone and did not differ significantly from clindamycin treatment. Electron micrographs revealed markedly less cell-adherent glycocalyx on organisms grown in vitro treated with clindamycin versus penicillin and controls. It is hypothesized that clindamycin inhibits glycocalyx production in vivo, allowing better antimicrobial penetration in the infected cardiac vegetation.

Animals

Phase II study of vinblastine in previously treated squamous carcinoma of the cervix. A Gynecologic Oncology Group study.

Thirty-six patients with advanced squamous carcinoma of the uterine cervix recurrent after radiotherapy or surgery or first-line chemotherapy were eligible for a phase II study employing vinblastine in a dose of 9 mg/m2 intravenously every 3 weeks until disease progression or toxicity supervened. Two patients were never treated, leaving 34 patients evaluable for toxicity. One patient was inevaluable for response, leaving 33 evaluable for this parameter. Thirty-two patients had prior radiotherapy and 30 had prior chemotherapy. All patients had Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2. Median age was 46 years. Twenty patients had disease in the pelvis and 13 had extrapelvic metastases. Fourteen patients had grade 3 lesions. A median of three courses (range: 1-12 courses) was administered. Ten patients (29.4%) experienced GOG grade 3 or 4 leukocytopenia and 10 had grade 3 or 4 granulocytopenia. Other toxicity included grade 4 gastrointestinal toxicity and anemia in one patient each and two patients with grade 3 neurotoxicity. Twenty patients (60.6%) had stable disease with therapy and 13 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in previously treated patients with squamous carcinoma of the cervix.

Adult

Effect of pulsed ultrasound versus placebo on muscle soreness perception and muscular performance.

The purpose of this study was to compare the analgesic effect of pulsating ultrasound treatment and placebo on delayed onset of muscle soreness produced by an eccentric exercise bout. In addition, the effect of pulsed ultrasound on muscular performance following an eccentric exercise bout was studied. Eighteen untrained subjects were randomly assigned to: 1) ultrasound (A) [N = 6] over the areas of concentrated muscle soreness, i.e. proximal vastus lateralis and distal vastus medialis; 2) placebo ultrasound (B) [N = 6]; and 3) no therapeutic intervention (C) [N = 6]. Baseline data were recorded for maximum isometric knee extension contraction (MVC), maximum knee extension torque (MT), knee extension work (W), and soreness perception (SP). All values were subsequently reassessed 24 and 48 hours after intense muscular activity. Immediately following the 24 hour reassessment the A group received ultrasound treatment, the B group received placebo ultrasound, while the C group received no treatment. Percent deviation from baseline of SP, MVC, MT and W were significantly less for A than B and C (p less than 0.05) at 48 hours post muscle soreness bout. These data indicate that pulsed ultrasound accelerates restoration of normal muscle performance, and thus is effective in decreasing delayed onset of muscle soreness. The mechanism for decreasing soreness perception in the muscle is unknown, but may be related to decreasing intramuscular pressure and/or decreasing the inflammatory response.

Adult

Characterization of normal human exocervical epithelial cells immortalized in vitro by papillomavirus types 16 and 18 DNA.

An in vitro system for studying the interaction between human papillomavirus (HPV) 16 and 18 recombinant DNA and normal human exocervical epithelial cells is described. Eight HPV-immortalized human exocervical epithelial cell lines were established; all the lines contained either integrated HPV16 or 18 sequences and expressed HPV mRNAs. Thus, integration and expression appear to be required for immortalization. Immortalized cells (greater than 200 population doublings to date) divided rapidly (doubling time of 30 to 46 h) and morphologically resembled primary cultures of normal human exocervical epithelial cells. They expressed a keratin pattern consistent with their origin from exocervical epithelium. When cultured at high density or in the presence of serum they terminally differentiated. Sublines resistant to terminal differentiation were selected by growth in serum-supplemented medium. Keratin pattern changes suggest they have some properties in common with cervical squamous carcinoma cells. However, HPV-immortalized cell lines were not tumorgenic in nude mice. Thus, HPV16/18 is not carcinogenic by itself. These cell lines represent an appropriate model for studying factors that regulate HPV gene expression in normal cervical epithelial cells and examining the influence of cocarcinogens on neoplastic progression.

Animals

Possible prognostic significance of human papillomavirus type in cervical cancer.

While several different human papillomaviruses (HPV) have been associated with cancer of the cervix, it is yet to be determined if specific HPV types have clinical or prognostic significance. To address this question, 30 cases of invasive carcinoma (squamous carcinoma, adenosquamous carcinoma, and adenocarcinoma) with HPV DNA sequences detectable in the tissue were analyzed. HPV type was determined by Southern blot DNA hybridization. Clinical information was obtained by chart review, and all biopsy and surgical specimens were reviewed microscopically without knowledge of HPV type. HPV 16 was detected in 14 cases, HPV 18 in 6, and HPV 31 in 2. In eight samples there were distinctly different, but as yet uncharacterized, HPV DNAs. Of the factors evaluated, tumor grade was found to have a statistically significant relationship to HPV type. Eighty-three percent of HPV 18-associated tumors were grade 3 tumors (5 of 6) as compared to only 7% of HPV 16-associated tumors (1 of 14) (P = 0.002). Age at diagnosis and nodal status in relation to HPV type exhibited a trend but were not statistically significant. The mean age of the HPV 18 group was 37 years, compared to 49 years for the HPV 16 group. Similarly, among Stage IB cancers, nodal involvement was associated with 60% of HPV 18 cases (3 of 5) as compared with 36% of HPV 16 cases (4 of 11). These observations suggest that HPV 18 may be associated with a more aggressive form of cervical cancer than other HPV types.

Adenocarcinoma

Diagnostic accuracy of fever as a measure of postoperative pulmonary complications.

Various prevalence rates have been estimated for pulmonary complications after abdominal surgery, and fever has been thought to be a diagnostic indicator. This study quantifies the diagnostic accuracy of fever as a measure of postoperative pulmonary complications and includes the sensitivity, specificity, and positive and negative predictive values. Assessments using fever and chest x-ray film were determined for 270 patients after elective intra-abdominal surgery in three hospitals with six practicing surgeons in a Southern Ontario city. With use of reliable chest x-ray reports indicating lung pathologic findings as positive for pulmonary complication, the prevalence of a positive finding was 57%. The prevalence of a fever (temperature greater than or equal to 38 degrees C) was 40%. The sensitivity and negative predictive value of fever were slightly below 50%, and the specificity and positive predictive value of fever was 68% and 66% respectively. Fever was an accurate indicator of x-ray evidence of atelectasis in only 56% of the subjects. Therefore, neither the presence nor the absence of fever can assure clinicians of the presence or absence of a postoperative pathologic pulmonary complication such as atelectasis.

Abdomen

The significance of paraaortic node status in carcinoma of the cervix and endometrium.

Survival in 115 women with cervical carcinoma and 55 patients with carcinoma of the endometrium was correlated with the status of paraaortic lymph nodes and the clinical stage of disease. The survival probability at 48 months for patients with cervical cancer who had negative paraaortic lymph nodes was 86% for stage IB in comparison to 67% for those with advanced disease (clinical stages II, III, and IV). The difference of 19% between these two groups was not statistically significant nor was there a statistical difference in survival between early and advanced disease groups when paraaortic nodes contained tumor (37 vs 20%). For all stages of cervical cancer, survival was 80% with negative nodes and 20% with positive nodes at 48 months. In patients with endometrial carcinoma and negative paraaortic lymph nodes, projected survival at 48 months was 72% for stage I and 77% for stages II and III. When paraaortic lymph nodes demonstrated metastatic disease, survival uniformly decreased to 27% of patients with stage I cancer and 25% of those with stage II and III disease. For all stages of endometrial cancer, survival was 76% with negative nodes and 26% with positive nodes at 48 months. The presence or absence of metastatic disease in the paraaortic lymph nodes is an important prognostic factor that appears to be more useful in predicting survival than clinical stage of disease in patients with cervical and endometrial cancer.

Adenocarcinoma

Signal sequence of alkaline phosphatase of Escherichia coli.

The amino acid sequence of the signal sequence of phoA was determined by DNA sequencing by using the dideoxy chain termination technique (Sanger et al., Proc. Natl. Acad. Sci. U.S.A. 74:5463-5467, 1977). The template used was single-stranded DNA obtained from M13 on f1 phage derivatives carrying phoA, constructed by in vitro recombination. The results confirm the sequence of the first five amino acids determined by Sarthy et al. (J. Bacteriol. 139:932-939, 1979) and extend the sequence in the same reading frame into the amino terminal region of the mature alkaline phosphatase (Bradshaw et al., Proc. Natl. Acad. Sci. U.S.A., 78:3473-3477, 1981). As was predicted (Inouye and Beckwith, Proc. Natl. Acad. Sci. U.S.A. 74:1440-1444, 1977), the signal sequence was highly hydrophobic. The alteration of DNA sequence was identified for a promoter mutation that results in the expression of phoA independent of the positive control gene phoB and in insensitivity to high phosphate.

Alkaline Phosphatase