Different Bla-g T cell antigens dominate responses in asthma versus rhinitis subjects.

BACKGROUND AND OBJECTIVE: The allergenicity of several German cockroach (Bla-g) antigens at the level of IgE responses is well established. However, less is known about the specificity of CD4+ TH responses, and whether differences exist in associated magnitude or cytokine profiles as a function of disease severity. METHODS: Proteomic and transcriptomic techniques were used to identify novel antigens recognized by allergen-specific T cells. To characterize different TH functionalities of allergen-specific T cells, ELISPOT assays with sets of overlapping peptides covering the sequences of known allergens and novel antigens were employed to measure release of IL-5, IFNγ, IL-10, IL-17 and IL-21. RESULTS: Using these techniques, we characterized TH responses in a cohort of adult Bla-g-sensitized subjects, either with (n = 55) or without (n = 17) asthma, and nonsensitized controls (n = 20). T cell responses were detected for ten known Bla-g allergens and an additional ten novel Bla-g antigens, representing in total a 5-fold increase in the number of antigens demonstrated to be targeted by allergen-specific T cells. Responses of sensitized individuals regardless of asthma status were predominantly TH 2, but higher in patients with diagnosed asthma. In asthmatic subjects, Bla-g 5, 9 and 11 were immunodominant, while, in contrast, nonasthmatic-sensitized subjects responded mostly to Bla-g 5 and 4 and the novel antigen NBGA5. CONCLUSIONS: Asthmatic and nonasthmatic cockroach-sensitized individuals exhibit similar TH 2-polarized responses. Compared with nonasthmatics, however, asthmatic individuals have responses of higher magnitude and different allergen specificity.

Long-term follow-up of stage I cervical adenocarcinoma treated by radical surgery.

From 1972 to 1988 55 patients underwent radical abdominal hysterectomy, pelvic lymph node dissection for treatment of FIGO Stage I cervical adenocarcinoma. A minimum of 60 months follow-up was available on all surviving patients. A detailed retrospective analysis was conducted to determine the influence of radical surgery on survival and to identify prognostic factors for recurrence. A bilateral salpingo-oophorectomy was included as part of the primary surgery in 52 the patients. Histologic subtypes included endocervical adenocarcinoma (44), papillary carcinoma (5), clear cell carcinoma (3), and adenosquamous carcinoma (3). The 5- and 10-year disease-free survival was 85.5%. The median follow-up of the surviving patients was 78.5 months (range, 60 to 240 months). Eight patients recurred, all but 1 of whom died of disease. Median time to recurrence was 28 months (range, 6 to 47 months). Five patients recurred beyond 24 months. One patient recurred locally, 5 recurred regionally, and 2 developed distant recurrences. Lymph node metastases (P < 0.0001), histologic grade (P < 0.0001), depth of invasion (P = 0.0001), presence of paracervical disease (P = 0.0034), and size of the lesion (P = 0.0059) were shown to be significant determinants of recurrence. Two of the 3 patients with a single involved lymph node recurred. Age, parity, history of oral contraceptive use, histologic subtype, and lymph vascular space involvement were not statistically significant determinants of recurrence. Adjuvant whole pelvic radiotherapy did not influence regional recurrence or survival but may decrease local recurrence. Radical abdominal hysterectomy pelvic lymph node dissection is an appropriate treatment of patients with Stage I cervical adenocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

High-dose, short-duration cisplatin/doxorubicin combination chemotherapy for advanced ovarian epithelial cancer.

Sixty-one patients with epithelial ovarian cancer were treated with intensive high-dose, short-course chemotherapy that consisted of cisplatin (120 mg/m2) and doxorubicin (70 mg/m2) every 3 weeks for four cycles. Patients in complete clinical remission were offered second-look laparotomy (SLL). Patients with minimal or no residual disease at SLL were randomized to either cyclophosphamide (1000 mg/m2 every 21 days for six cycles) or whole-abdominal radiation therapy. All patients completed therapy with a median leukocyte nadir 1.3/microliter and platelet nadir of 90/microliters. Forty-five patients (74%) had a complete clinical response. Results of twenty-two of 36 second-look procedures (64%) showed no evidence of disease (NED). After SLL, 19 patients received six courses of cyclophosphamide and 16 patients received whole-abdominal radiation. Nine patient who refused SLL and one patient with negative SLL findings refused additional treatment. The median survival time for all patients was 51.3 months. High-dose intensive chemotherapy regimens have high response rates, but survival needs to be compared with traditional low-dose regimens. Although high-dose cisplatin and doxorubicin were myelosuppressive, the resulting complications were manageable. There was no significant difference between the mean survival times of patients receiving Cytoxan, abdominal radiation, or no treatment as second-line therapy.

Ultrasonic surgical aspiration in the treatment of vulvar disease.

Ultrasonic surgical aspiration is a useful technique for safe and accurate tissue removal. This study was conducted to evaluate its role in noninvasive vulvar disease. From December 1988 to March 1990, 27 patients underwent ultrasonic surgery; nine patients had vulvar intraepithelial neoplasia (VIN) and 18 had condylomata acuminata. All surgical procedures were done under general anesthesia, with two patients requiring hospitalization for perineal care and pain control after extensive vulvar surgery. Recurrent or persistent disease occurred in four patients with condylomata acuminata and in two with VIN, with a mean follow-up of 50 weeks. Reepithelialization was completed within 5 weeks and no patients developed vulvar scarring. Adequate samples for histopathologic review were obtained in 26 patients. Identical histologic grading occurred in all 13 patients who had preoperative vulvar biopsies and an adequate aspiration specimen. Ultrasonic surgery permits precise and rapid removal of epithelial lesions with rapid healing, minimal patient discomfort, excellent cosmetic results, and histopathologic documentation.

Peritoneal cytology in endometrial cancer: a review.

Utilization of literature review to evaluate peritoneal cytology as a test for the detection of malignant cells in the peritoneal cavity is limited by the size of the study populations, varied use of preoperative radiation, the lack of consistent methodology for specimen retrieval and processing, and the inherent subjectivity of cytologic interpretation. A standardized methodology for retrieval and processing of peritoneal cytologic specimens should be developed to allow meaningful comparisons of future studies. However, certain conclusions are permitted from published data: 1. The incidence of positive peritoneal cytology is 11.4 per cent among 3091 patients with FIGO stage I endometrial cancer. 2. The depth of the uterus does not influence the incidence of positive peritoneal cytology. 3. Positive peritoneal cytology is predictive of other known prognostic factors including advanced histologic grade, depth of myometrial invasion, and pelvic/periaortic lymph node metastases. 4. The presence of malignant cells in the peritoneal washings from some patients with no myometrial invasion and the high incidence of lymph node metastases in other patients with positive peritoneal cytology suggest that malignant cells gain access to the peritoneal cavity in a variety of ways. It is unclear whether each of these modes of access result in viable tumor cells with the potential for viable metastasis. The high incidence of lymph node metastasis in such patients suggests that lymphatic dissemination of malignant cells plays a significant role in the development of positive peritoneal cytology. In this setting positive peritoneal cytology clearly identifies that individual at high risk for recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of indium-111-labeled OC-125 monoclonal antibody in the detection of ovarian cancer.

This is a preliminary study to evaluate the utility of using the monoclonal antibody (CO-125) labeled with indium-111 to image recurrences of ovarian cancer. This technique has been investigated in 23 patients with ovarian cancer and the results have been compared with blood OC-125 levels, CT scans, and findings at second-look surgery. Following infusion of 1 mg of F(ab')2 fragments (1-2 mCi 111In), quantitative SPECT and planar imaging was obtained daily for 72 hr along with analysis of serum. The nuclear medicine scans of the tumor site recurrences were technically excellent. When compared to second-look laparotomy, there were 2 true negatives, 2 false positives, 14 true positives, and 2 false negatives by nuclear imaging. CT scans correlated less well with surgery, but serum OC-125 levels correlate more closely with nuclear scans and second-look surgery. Those with multiple small metastatic implants showed a pattern of diffuse uptake which increased with time, whereas those with nodal or larger recurrences showed a more focal uptake. The combination of favorable biodistribution and positive images, especially in patients with normal antigen levels and negative CT scans, suggests a role for OC-125 monoclonal antibody imaging in their clinical management. However, further investigation is needed to determine whether nuclear scans can replace second-look surgery. If it can show that enough 111In-labeled antibody accumulates in the tumor site to justify radioimmunotherapy, then 90Y (a pure beta emitter) could be exchanged for 111In. This is potentially a method of radioimmunotherapy for recurrent ovarian carcinoma.

Prophylactic topical cefamandole in radical hysterectomy.

From July 1, 1978 to June 30, 1984, 45 radical abdominal hysterectomies were performed by the authors at Tripler Army Medical Center. Management was uniform except for the use of prophylactic antibiotics. Three patterns of practice were identified: Group I, no antibiotics were used; Group II, intravenous (i.v.) antibiotics were given in the induction room and for less than 48 h post-surgery; Group III, prophylactic i.v. antibiotics were given and the surgical site was also irrigated with a cefamandole and saline solution. The three groups were found to be similar with regard to age, parity, weight-height index, pre- and postoperative hematocrit, pre-operative white blood cell count, operative and anesthesia times, estimated blood loss, and amount of blood transfused. Groups I and II had a higher surgical site infection rate (87.5% and 63.6%, respectively) than Group III (3.8%). The mean 10-day fever index in degree hours was 109 for Group I, 71 for Group II, and 30 for Group III (P less than 0.001). Irrigation of the surgical site with a cefamandole and saline solution in addition to i.v. antibiotics decreases the infectious morbidity of radical hysterectomy.

Peritoneal cytology in stage I endometrial cancer.

Peritoneal lavage fluid for cytologic study was obtained in 73 patients undergoing primary surgery for stage I endometrial adenocarcinoma. Preoperative irradiation was not used. Malignant cells consistent with endometrial adenocarcinoma were present in eight (11 percent) cases. There was no significant difference in the proportion of patients with "positive peritoneal cytology" when patients with grade 1 and 2 tumors, five of 45 (11 percent), were compared with those with grade 3 and adenosquamous tumors, three of 28 (10.7 percent), between deeply invasive tumors, two of 20 (10 percent), and those with superficial or no invasion, six of 52 (11.5 percent), between stage IA, six of 42 (14.5 percent) and stage IB disease, two of 31 (6.5 percent). The prevalence of positive peritoneal cytology in this series of 73 patients who received no preoperative irradiation is similar to that reported in other series where preoperative irradiation was used. No correlation between positive peritoneal cytology and other reported poor prognostic indicators in stage I endometrial adenocarcinoma was found.

A prospective randomized study of doxycycline as a prophylactic antibiotic in patients undergoing radical hysterectomy.

A prospective randomized study was undertaken to evaluate doxycycline as a prophylactic antibiotic in patients undergoing radical abdominal hysterectomy and pelvic lymphadenectomy. Although 69 patients were initially randomized, 64 patients (34 study, 30 control) are the basis of this report: 5 patients were omitted because large pelvic lymph nodes positive for tumor were found at laparotomy and radical hysterectomy was abandoned. The two study groups were similar in both preoperative and operative risk factors. There was a statistically significant reduction in the 7- and 14- day febrile index in the doxycycline group. The rate of cuff and/or pelvic cellulitis was 2.3 times higher in the control group. Thus, single-dose doxycycline as a prophylactic antibiotic reduced both febrile morbidity and the rate of serious infections in the radical hysterectomy patient.

Alternating multiagent chemotherapy for advanced ovarian cancer.

A chemotherapy regimen consisting of hexamethylmelamine (H) 150 mg/m2 orally days 1-14, cyclophosphamide (C) 500 mg/m2 IV day 1 of a 28-day cycle with Adriamycin (A) 40 mg/m2 IV day 1 alternating with cis-diamminechloroplatinum (C-P) 50 mg/m2 IV day 1 every other cycle was administered to 29 patients with advanced epithelial ovarian cancer. Toxicity to this regimen included alopecia, nausea, and vomiting in all patients. Mild paresthesias occurred in four patients. Hematologic toxicity required only minimal dose modification. There was no cardiac, renal, or auditory toxicity. The clinical response rate of 55% and median survival of 14 months compare favorably with that of other reported series. This chemotherapy regimen seems to be well tolerated without jeopardizing the patients' response.

Ip immunotherapy and chemotherapy in advanced epithelial ovarian cancer.

Nine patients with advanced epithelial ovarian cancer, classified as either stage III with macrometastatic residual disease or stage IV, received combination chemotherapy in conjunction with ip rabbit-derived human ovarian antitumor serum (HOATS). The HOATS regimen consisted of the ip instillation of 100 ml of ovarian antitumor serum on Days 1 and 3 of the first chemotherapy cycle. Side effects attributable to HOATS were low-grade fever in three patients and diffuse skin rash in two. The 1-year cumulative survival was 87%, with a clinical response rate of 80%. No significant toxic reactions to HOATS have been observed. Continuation of the present study seems justified.

Prevention of endomyometritis using antibiotic irrigation during cesarean section.

After double-blind controlled studies demonstrated cefamandole nafate irrigation of the uterus during cesarean section to be effective in reducing the rate of endomyometritis, antibiotic irrigation was adopted as a standard procedure at Tripler Army Medical Center. The present study analyzes the outcome in patients undergoing cesarean section before (comparison group) and after (treatment group) routine use of antibiotic irrigation began. The incidence of endomyometritis in 100 patients from the comparison group was 20% and in 298 patients from the treatment group 1.7% (P less than .0001). Serum analysis for cefamandole nafate demonstrated little systemic absorption of the antibiotic. Cefamandole nafate intrauterine irrigation at cesarean section effectively prevents endomyometritis.

Febrile morbidity following cefamandole nafate intrauterine irrigation during cesarean section.

The effectiveness of intrauterine irrigation during cesarean section with a solution of cefamandole nafate in reducing febrile morbidity was studied in a prospective double-blind fashion. Ninety patients who were undergoing cesarean section at Tripler Army Medical Center were randomized into three groups: (1) intrauterine irrigation with cefamandole nafate solution, (2) intrauterine irrigation with normal saline solution, and (3) no irrigation. Febrile morbidity was evaluated by means of a fever index. There was a statistically significant reduction in the fever index in the group that received intrauterine irrigation with cefamandole nafate. The incidences of clinically diagnosed endomyometritis in the three groups were 0%, 26.7%, and 23.3%, respectively. Prophylactic intrauterine irrigation with cefamandole nafate during cesarean section markedly reduces febrile morbidity, primarily by reducing the incidence of endomyometritis.

The diagnosis and management of cervical intraepithelial neoplasia in the patient under the age of twenty-one.

The diagnosis and management of 260 patients between the ages of 15 and 21 with cervical intraepithelial neoplasia is discussed. These patients represented 22% of all new patients seen in the Colposcopy Clinic of The Johns Hopkins Hospital between January 1975 and December 1979. Sixty-six percent of the patients were referred for evaluation of two Papanicolaou smears which were compatible with the diagnosis of CIN I while only 1.5% of the patients were referred with the cytologic diagnosis of CIN III. The colposcopic impression in the majority of patients was CIN I. There was excellent correlation between the colposcopic impression and histopathology. Thirteen percent of the patients evaluated had surgical procedures, 11% (29 patients) under-went conization and 2% (five patients) hysterectomy. The majority of patients under the age of 21 had minimal degree of cervical intraepithelial neoplasia. The importance of conservative management is discussed.

Intrauterine irrigation with cefamandole nafate solution at cesarean section: a preliminary report.

The effectiveness of intrauterine irrigation with an antibiotic solution of cefamandole nafate in reducing the incidence of endometritis after cesarean section was studied in a prospective, double-blind fashion. Ninety patients who underwent cesarean section at Tripler Army Medical Center were divided into three equal groups. Each group received one of the following treatments at the time of operation: (1) intrauterine irrigation with the antibiotic solution, (2) irrigation with normal saline solution, or (3) no irrigation. The resulting incidences of endometritis were 0%, 26.7%, and 23.3%, respectively. Intrauterine irrigation with cefamandole nafate solution at the time of cesarean section significantly reduced the incidence of endometritis.

Single-dose and multidose prophylaxis in vaginal hysterectomy: a comparison of sodium cephalothin and metronidazole.

A total of 79 patients underwent vaginal hysterectomy and were randomly assigned to three regimens of prophylactic antibiotics: multidose intravenous sodium cephalothin, single-dose intravenous sodium cephalothin, and single-dose oral metronidazole. Control groups were selected from two previous studies conducted at our institution. The incidence rates of infectious morbidity following all three regimens of antibiotics were substantially lower than in the control groups. There was no statistically significant difference in the incidence of standard febrile morbidity and serious pelvic infections among the three groups. The fever index was lowest in the single-dose sodium cephalothin group.