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Biomedical subjects

A J Jacobs

Publications and source records attributed to A J Jacobs.

At least 37 records · Page 2Linked to original sources

Mullerian adenosarcoma of the cervix with heterologous elements: diagnostic and therapeutic approach.

Mullerian adenosarcoma of the cervix with heterologous elements is an extremely rare tumor first described by Roth and colleagues (L. M. Roth, G. L. Pride, and H. M. Sharma, Cancer 37, 1725-1736) in 1976. Since that time there have been only three subsequent reports of these cervical Mullerian adenosarcomas, which seem to occur most often in the postmenarchal age group. Due to the paucity of cases and the unknown biological potential of the tumor, therapy has ranged from simple excision to radical pelvic surgery and vaginectomy combined with both radiotherapy and chemotherapy. We report another case of Mullerian adenosarcoma of the cervix occurring in a teenage woman and make recommendations about diagnostic and therapeutic measures available to the physician.

Adolescent↗

Inhibition of proliferation of lines derived from human cervical carcinomas by cytotoxic drugs and by recombinant interferons.

The authors studied the effects of recombinant interferons (IFN), doxorubicin, and cisplatin against three cell lines derived from human epidermoid cervical carcinomas. These lines were SW 756, containing the genome of human papillomavirus (HPV) type 18, and CaSki and SiHa, containing HPV type 16. IFN-gamma suppressed the growth of all three lines, with a plateau in inhibitory effect beyond a concentration of 1000 units/ml. IFN-alpha was effective in this regard only against SW 756. In this line, the two IFNs together inhibited cell replication to a greater extent than the maximal effect of either IFN alone. Doxorubicin exerted a dose-dependent cytotoxic effect against all the lines, while cisplatin exhibited cytotoxicity only against SW 756. Doxorubicin and IFN-gamma, when used together, acted synergistically against CaSki and SiHa, and in an additive manner against SW 756.

Carcinoma, Squamous Cell↗

A rapid DNA probe test for detecting human papilloma virus types 6/11 and 16 in biopsy specimens.

A simple, rapid and sensitive non-radioactive in situ hybridization assay for human papillomavirus (HPV) has been developed and used to detect HPV 6/11 and HPV16 DNA in ano-genital biopsy specimens. A comparative study to determine the sensitivity and the specificity of this assay relative to Southern blot hybridization assays was performed using one hundred biopsy specimens. The sensitivity of the in situ hybridization assay was 88% for HPV type 6/11 and 89% for HPV type 16. The specificity of the test was 99% for both virus types. In addition to its high sensitivity and specificity, this in situ hybridization assay for HPV uses a non-radioactive detection system. The assay is faster and easier to perform than the Southern blot method. Also, in situ hybridization assays permit the simultaneous evaluation of the histology, as well as the DNA content of biopsy tissues because they do not result in the destruction of tissue or cell morphology. This prototype HPV DNA assay was developed using DNA probes for HPV 6/11 and HPV 16 DNA in anogenital biopsy specimens. However, the protocol developed in these studies can easily be extended to include the use of probes for detecting other HPV types in a variety of tissues.

Anal Canal↗

Viral agents in two-stage cervical carcinogenesis: an experimental study in mice.

The role of chemical and viral agents in the development of cervical cancer in mice was studied by repeated carcinogen applications, repeated intravaginal instillations of HSV type II virus, and single carcinogen application as initiating agent followed by repeated instillations of virus as promoter. In all the animals studied, repeated applications of 9,10-dimethylbenzanthracene (DMBA) induced dysplastic conditions of the cervix and vagina, mild, moderate, and severe, as well as a large number of invasive squamous cell carcinomas. DMBA alone as initiating agent did not induce tumors or marked dysplasia; when followed by repeated applications of HSV2 virus only mild dysplastic lesions occurred. Repeated applications of HSV2 alone produced inflammatory changes of the cervix and vagina. It is concluded that repeated intravaginal instillation of HSV2 virus as done in this study does not induce cervical cancer or its precursors, and in a two-stage system is only weakly a promoter of carcinogen-induced latent tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗

Phase I/II study of definitive radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) for advanced or recurrent gynecologic malignancies. Preliminary report.

Twenty-three patients with advanced gynecologic malignancy were treated with definitive irradiation and synchronous sensitizing chemotherapy (CT) consisting of cisplatin (CDDP), 50 mg/m2 i.v. rapid infusion, and a 5-day continuous infusion of 5-fluorouracil (5-FU), 750 mg/m2/day. A total of three cycles were administered every 3-4 weeks. Fifteen patients had primary cervical epidermoid carcinoma (three bulky stage IIB, one stage IIIA, ten stage IIIB, one stage IV), four had pelvic recurrences of carcinoma of the cervix, two had endometrial adenocarcinomas (stage IV), and two had vulvar epidermoid carcinoma (one stage III and one stage IV). Radiotherapy (RT) for implantable tumors consisted of 2,000 cGy whole pelvis, 3,000-4,000 cGy split field, and two intracavitary or interstitial insertions, resulting in a total dose of 7,500-8,000 cGy to point A. Three courses of CT were delivered simultaneously with irradiation of the central bulk of tumor: during the first week of whole pelvis RT and with each of the two brachytherapy procedures. Nonimplantable tumors were treated with protracted external beam RT (5,500 cGy tumor dose) and three courses of CT during weeks 1, 4, and 7 of RT. Twenty-one of 23 patients completed RT and 18 of 23 patients completed CT as planned, but half had delays in either RT or CT. Grade 2 or 3 late sequelae consisted of leg edema (one patient), proctosigmoiditis (one patient), bowel obstruction (one patient), vesicovaginal fistula (one patient), and pulmonary embolus (two--one fatal). The incidence of grade 2 and 3 sequelae were 18 and 22%, respectively. With 1-3 years of follow-up evaluation, 12 of 23 (52%) patients are free of disease, and 9 of 22 evaluable patients (41%) have had failure within the pelvis. We conclude that high-dose definitive RT can be delivered with synchronous CDDP and 5-FU at the doses given, with acceptable toxicity. Further study is required to evaluate the impact of radiosensitization on tumor control and late morbidity of therapy. Optimization of irradiation and drug doses as well as the best schedules that may enhance the interaction of these two modalities should be further investigated.

Adenocarcinoma↗

Mesenteric cysts in pregnancy. A case report.

Mesenteric cysts are rare. These large, often asymptomatic growths may be misinterpreted easily by the clinician as representing either benign or malignant ovarian tumors, renal masses, or hepatic tumors or cysts. We treated a women for a mesenteric cyst complicating her second pregnancy. Because of the increasing use of ultrasound in a wide variety of pregnancy complications, and because of the mesenteric cysts's unique sonographic appearance (resembling that of a benign ovarian tumor), such a cyst must be included in the differential diagnosis of large, cystic abdominal masses in pregnancy.

Adult↗

Serum copper in ovarian carcinoma.

The serum copper and CA 125 levels of 31 patients with epithelial ovarian carcinoma were determined. Serum copper was elevated in seven patients and CA 125 was elevated in 22 patients. A rise in serum CA 125 always was associated with disease progression. In comparison, serum copper fluctuation did not correlate with the natural history of the malignancy. We concluded that serum copper determination has no use in epithelial ovarian carcinoma management.

Antigens, Neoplasm↗

Therapy of ovarian carcinoma: the relationship of dose level and treatment intensity to survival.

Following primary maximal cytoreduction, 71 previously untreated patients with advanced epithelial ovarian carcinoma received at least six courses of combination chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide. The cumulative dose (CD) through three (CD3) and six (CD6) courses was calculated for each drug and for all drugs combined. The dose intensity (DI) through three (DI3) and six (DI6) courses was calculated for each drug by dividing CD3 and CD6 by the interval (in weeks) between surgery and the third and sixth course. The interval from surgery to the third or sixth course had no effect on survival. Similarly, there was no significant difference in survival between patients with high and low CD3 or CD6 for any drug or for all drugs combined. Patients with high DI6 for cisplatin, doxorubicin, and all drugs combined survived significantly longer than those with low DI6. The survival difference for patients with high and low DI6 for cyclophosphamide approached, but did not attain, statistical significance at the 0.05 level. The intensity with which combination chemotherapy is administered may have an impact upon survival in patients with ovarian carcinoma.

Actuarial Analysis↗

Mini-colpostats in the treatment of carcinoma of the uterine cervix.

Between 1976 and 1982, 293 patients were treated for carcinoma of the uterine cervix at Washington University by definitive radiotherapy consisting of external beam therapy and two standard Fletcher-Suit applications (tandem plus vaginal colpostats). In ninety-nine patients (34%) mini-colpostats (MC) were used for one or both of their intracavitary insertions while 194 (66%) patients were treated twice with regular Fletcher-Suit colpostats (RC). The frequency of MC use was related to the age and parity of the patients. The distribution by stage of MC and RC groups was not significantly different. Pelvic failure in the MC group was similar to that of the RC group (21% vs 24%). Five-year disease-free survival was also similar between the two groups: 86% vs 80% Stage IB, 57% vs 61% Stage IIA, 47% vs 52% Stage IIB, and 27% vs 45% Stage III for MC and RC groups, respectively. The rate of major complications (grade 3) was 15% in the MC group and 8% in the RC group (p = 0.08). Careful phantom dosimetric studies in both types of colpostats and correlations of dose distributions at various points in the pelvis with frequency of rectal and bladder complications were carried out. The bladder and rectum received a 5-10% higher mean radiation dose (Gy) in the MC group than in the RC group despite lower overall exposure (milligram-hours). Thermoluminescent dosimetry in a polystyrene phantom demonstrates that approximately 10% higher doses are delivered to the bladder, rectum, and point A with an MC system as compared to an RC system, for constant exposure in mgh. Phantom measurements of a newer MC with bladder and rectal shielding demonstrate no influence on the bladder and rectal point dose at a source separation of 3 cm; midline points of the bladder and rectum are not within the full shadow of the shields even if the colpostats are flush with the tandem. Implications for therapy are discussed.

Brachytherapy↗

Protection of mice against fission neutron irradiation by WR-2721 or WR-151327.

Two phosphorothioate compounds, WR-2721 and WR-151327, were examined for their radioprotective efficacies against the effects of fission neutron irradiation in male and female mice. Within sex groups no significant difference in lethality at 30 or 100 days postirradiation was found between WR-2721 or WR-151327 pretreatment. The dose modification factors (DMFs) for male mice treated with either compound were 1.29 (LD50/30) and 1.24 (LD50/100), and those for drug-treated female mice were 1.21 (LD50/30) and 1.19 (LD50/100). Both WR-2721 and WR-151327 were found to be equally radioprotective when compared using DMFs as the end point. WR-151327 (500 mg/kg, ip) was found to be significantly more toxic to both male and female B6D2F1 mice than equimolar amounts of WR-2721. Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice. In addition, sex differences were noted in drug toxicity. Toxic death in female mice given WR-151327 (500 mg/kg, ip) is 2.6 times more probable than in males.

Amifostine↗

Carcinoma of the fallopian tube. Management and sites of failure.

Thirty patients with adenocarcinoma of the fallopian tube, treated between 1950 and 1981, were studied. Median age was 55 years, and mean parity was 1.3. Bleeding or discharge occurred as a presenting complaint in 47% of patients, abdominal distention or mass in 50%, and pain in 30%. Lesions were staged using a system analogous to the International Federation of Gynecology and Obstetrics (FIGO) classification for ovarian carcinoma. Nine patients had Stage I disease; 11, Stage II; 7, Stage III; and 3, Stage IV. Histologic differentiation was Grade 1 in 39% of the patients, Grade 2 in 18%, and Grade 3 in 43%. Primary surgical treatment consisted of total abdominal hysterectomy and bilateral salpingectomy in 70% of the patients; 23% had more extensive surgery, whereas 13% had less extensive surgery. Three patients with Stage I tumors were treated with surgery alone, and the remainder received postoperative radiation, chemotherapy, or both. Survival was unrelated to grade, but highly dependent upon stage. Survival at 5 years was 56% for Stage I, 27% for Stage II, 14% for Stage III, and 0% for Stage IV. Four of five patients treated after surgery with a combination of cisplatin, doxorubicin, and cyclophosphamide (PAC) survived at least 3 years. Patterns of initial treatment failure showed 56% with a component of pelvic failure, 50% with a component of upper abdominal failure, and 44% with extraperitoneal metastases as a component of failure. These results suggest the need for aggressive postoperative adjuvant therapy targeted at upper abdominal and distant sites for metastasis in all lesions beyond Stage I.

Adult↗

Short-term persistence of carcinoma of the uterine cervix after radiation. An indicator of long-term prognosis.

Between 1959 and 1980, 590 evaluable patients received a full course of radiation therapy as primary treatment of invasive epidermoid carcinoma of the cervix. At follow-up visits conducted between 1 and 3 months after the completion of radiation, 72 patients had physical or biopsy findings indicative of persistent disease (PER), whereas an additional 36 had findings suggestive of tumor (SUS). The remaining 482 demonstrated a complete response (CR) by 1 month after the administration of treatment. The lower the stage, the more likely was a CR by 3 months (Stage I, 94.4%; Stage II, 86.2%; Stage III, 62.7%). A higher proportion of CR was obtained in patients with tumor of less than 5 cm in diameter than in those with tumors greater than 5 cm in diameter (82.4% versus 76.3%, respectively; 0.1 greater than P greater than 0.05). CR patients enjoyed a marked survival advantage over those with PER, whereas women with SUS demonstrated intermediate 5-year survival (76.0%, 41.5%, and 7.4%, respectively; P less than 0.0001). The same survival gradient of CR greater than SUS greater than PER was demonstrated when tumors of each stage were analyzed separately. There was no difference in survival between patients with PER or SUS at 1 month and those with PER or SUS at 3 months. The proportion of recurrent tumors diagnosed as exclusively distant metastases decreased from CR to SUS to PER. Analysis of dosimetry data suggests that the likelihood of CR was not a function of treatment variability. It was concluded that tumors that do not regress promptly are likely to recur, most with distant metastases. Such poor-prognosis patients should be targeted for early adjuvant or salvage therapy.

Actuarial Analysis↗

Effects of methylmercuric chloride, cycloheximide, and colchicine on the reaggregation of dissociated mouse cerebellar cells.

High fetal and neonatal brain levels of methyl mercury (MeHg) have been associated with the abnormal migration of neurons within the cerebellar and cerebral cortices. How MeHg interferes with cellular proliferation, migration, and differentiation is poorly understood. In this study, a cell recognition/cohesion assay based on the ability of dissociated neonatal mouse cerebellar cells to reaggregate was used to test whether MeHg exposure could disrupt cell surface recognition. Reaggregation of dissociated cells was monitored by measuring diameters from low-power photomicrographs. Exposure to 4 mg/kg body wt methylmercuric chloride (MeHgCl) 24 hr prior to the isolation of 3 days postnatal cerebellar cells altered the pattern of reaggregate growth. Between 25 and 51 hr in vitro (hiv), the exposed reaggregates grew at a faster rate than controls. Freshly isolated cells exposed in vitro to 0, 0.5, 1.0, and 4.0 microM MeHgCl initially exhibited a dose-related inhibition in reaggregate growth with an IC50 of 1.5 microM at 24 hiv. Following initial inhibition, exposed groups showed a dose-dependent acceleration in reaggregation similar to that found following in vivo exposure. In contrast, in vitro exposure to cycloheximide resulted in only a dose-related inhibition of reaggregation. No acceleration in growth rate was seen. Colchicine exposure produced no initial inhibition but appeared to mimic the long-term effects seen with both in vivo and in vitro MeHgCl exposure. These studies suggest that MeHgCl alters cerebellar cell recognition through a complex mechanism initially involving depressed synthesis of specific proteins followed by alterations in microtubules. Both effects may involve a disruption in the arrangement of specific cell surface recognition molecules.

Animals↗

Treatment of carcinoma of the fallopian tube using cisplatin, doxorubicin, and cyclophosphamide.

Nine patients with metastatic carcinoma of the fallopian tube were treated with a combination of cisplatin, doxorubicin, and cyclophosphamide. Three are in complete clinical remission following surgically documented complete response, at 18-56 months following the onset of chemotherapy. Two others died of intercurrent causes without evidence of disease. The remaining four died of tumor at 12, 23, 28, and 52 months following the initiation of treatment. Four second-look laparotomies were performed upon patients who were in complete clinical remission. No disease was found in any of these patients. It is concluded that this combination is an effective treatment for adenocarcinoma of the fallopian tube, and that second-look laparotomy may be useful in assessing response to chemotherapy in this disease.

Aged↗

Uterine neoplasms: MR imaging.

Magnetic resonance (MR) studies were performed on 20 healthy volunteers and 41 patients with proved cervical and uterine neoplasms. MR imaging demonstrated normal uterine landmarks in all patients. On T2-weighted images, the normal uterine wall could be differentiated into three distinct layers: a central high-intensity zone, a junctional low-intensity band, and a peripheral medium-intensity area. While most of the normal cervices had only two distinct zones (central high-intensity zone and peripheral low-intensity zone), a small percentage had three layers of signal intensity, similar to the uterine body. Primary cervical and uterine neoplasms could be identified on MR images. In 18 of 22 patients with proved carcinoma, a mass with a signal intensity higher than that of normal cervical lips was seen on T2-weighted images. Endometrial carcinoma was most often identified as expansion of the central high-intensity area; discrete tumor nodules were visible in nine of 15 patients. Mixed müllerian sarcoma appeared as a large pelvic mass with complete obliteration of normal uterine landmarks. MR imaging delineates primary cervical and endometrial carcinoma better than computed tomography does.

Adenocarcinoma↗