Short-term antibiotics treatment in patients with nasal polyps and enterotoxins producing Staphylococcus aureus strains.

Enterotoxins produced by Staphylococcus aureus (SA) can act as super-antigens and thus influence the course of chronic rhinosinusitis with nasal polyps (NP). The aim of this study was to determine if antibiotic treatment administered after endoscopic sinus surgery (ESS) for NP can positively influence the course of the disease compared to placebo. After ESS, 23 patients who tested positive, in a perioperative culture, for SA strains producing enterotoxins A-E and TSST-1, were randomized into two groups. Group A which in addition to standard treatment received oral anti-staphylococcal antibiotics for 3 weeks. Group B received a placebo. Both groups were compared preoperatively, and at 3 and 6 months after surgery using a symptom-specific score, an endoscopic score and the SNOT-22 quality of life questionnaire. Slightly better results were achieved in patients who received antibiotic therapy. However, the differences were not statistically significant. Regardless of post-operative treatment, approximately 30% of patients had a SA-negative culture 6 months after surgery.

The use of a pelvic displacement prosthesis to exclude the small intestine from the radiation field following radical hysterectomy.

OBJECTIVE: The goal of this study was to develop a device which will elevate the small intestine out of the pelvic cavity during radiation after radical surgery. METHODS: A prosthetic device of silicone plastic was designed which conforms to the pelvis. This device is filled with saline and renograffin for X-ray visualization. The capacity of the device is between 750 and 1500 cc. A small bowel contrast radiograph is performed prior to radiation to document exclusion from the radiation field. The device remains in place throughout radiation therapy and is then removed through a small incision after draining the contents of the prosthesis. RESULTS: Seven devices have been placed to date. The patients' age ranged from 35 to 65 years. All women had stage Ib1 carcinoma of the cervix and all underwent a type III radical hysterectomy with bilateral pelvic and common iliac lymphadenectomy. The indication for placement of the device was deep invasion of tumor in five patients, close margin in one patient, and positive pelvic lymph nodes in one patient. The amount of fluid instilled in the device ranged from 960 to 1200 cc. All patients had a return to normal bowel function within 3 days of surgery. All had radiologically documented exclusion of the small intestine from the radiation field prior to beginning radiation. In the postoperative period there was one major complication: a pulmonary embolism documented by pulmonary angiogram on postoperative day 2. All seven patients completed planned radiotherapy. The devices have been removed, with no adhesions to the prosthesis. CONCLUSIONS: The results of this study determine that the feasibility, safety, and efficacy of a prosthetic device in displacing the small bowel from the radiation field following radical surgery are sufficient to warrant a large-scale study. The device should be applicable to any and all tumors that require high dose pelvic radiation. It is expected that displacement of the small intestine from the radiation field will diminish overall complications and may allow delivery of radiation doses that approach colon and bladder tolerance.

Carboplatin as a radiation sensitizer in locally advanced cervical cancer: a pilot study.

Radiation therapy is the mainstay in treatment of locally advanced cervical carcinoma. Several chemotherapeutic agents have been used as radiation sensitizers in the treatment of cervical cancer in an effort to improve local response and survival. A prospective study was designed to evaluate carboplatin as a radiosensitizer in advanced cervical cancer. Standard radiotherapy techniques were used to treat patients with Stage IIA-IIIB cervical cancer. Intravenous carboplatin was administered twice weekly concurrent with external beam radiation. Of 22 evaluable patients, there were 19 complete responders of whom 15 remain alive: 11 patients were alive and disease free at last visit for a median duration of 15 months follow-up (range, 4-43 months) and 4 patients remain alive with disease for a median duration of 17 months (range, 3-55 months). Seven have died, one of whom was without evidence of disease. There were no treatment-related deaths and no grade 4 toxicity. The most significant adverse effect was hematologic resulting in four patients with grade 3 neutropenia or anemia. There were no fistulae or late gastrointestinal or genitourinary complications. This pilot study suggests that carboplatin administered with standard radiation is safe, well-tolerated, and thus may be useful as a radiation sensitizer in the treatment of locally advanced cervical cancer.

Residual disease in the uterus after preoperative radiotherapy and hysterectomy in stage IB cervical carcinoma.

Sixty-one patients with FIGO IB cervical cancer treated with planned preoperative radiotherapy (dose to point A: 52-93 Gy, mean 73 Gy) and hysterectomy from 1969 to 1993 were retrospectively reviewed. Patient characteristics and treatment parameters and their association with residual tumor in the hysterectomy specimen were analyzed. Glandular (adenocarcinoma and adenosquamous) tumors were smaller than squamous tumors: 6/11 (55%) were < 6 cm in diameter, versus 12/50 (24%) squamous tumors (p = 0.03). Glandular tumors had a higher incidence of residual disease: 10/11 (91%) versus 24/50 (48%) (p = 0.01). There was no association between presence of pathologic residual disease in the hysterectomy specimen and tumor size, morphology (endophytic vs. exophytic), patient age, dose to point A, time to deliver radiotherapy, or interval between radiotherapy and hysterectomy. Overall 34/61 (56%) patients had residual disease in their hysterectomy specimens after planned preoperative radiotherapy. There were significantly more glandular tumors than squamous tumors with residual disease, even though glandular tumors were a group of smaller tumors.

Inadequate adherence to radiotherapy in Latina immigrants with carcinoma of the cervix. Potential impact on disease free survival.

BACKGROUND: Radiation therapy plays an important role in the loco-regional control of carcinoma of the cervix. Strict adherence to the radiation protocol, without the introduction of time breaks, has been shown to favorably affect loco-regional control and survival, making adherence a crucial variable for optimal outcome. Because carcinoma of the cervix is a common disease among Latinas, with survival rates worse than those of other ethnic groups in this country, the pattern of adherence to the prescribed radiation treatment among Latina patients seen at Los Angeles County Hospital were studied. METHODS: The records of 69 consecutive Latina patients with cervical cancer who received radiation therapy at Los Angeles County Hospital were reviewed. Semi-structured interviews in a successive group of 30 similar patients were conducted to acquire preliminary information about their psychosocial characteristics. RESULTS: The results demonstrate inferior rates of optimal adherence to radiation treatment among Latina immigrant patients when compared with the rates reported in the literature for the general population of cervical cancer patients in United States (16 vs. 63%). Furthermore, a large subset of patients (20%) in the series elected to discontinue treatment without a medical reason. When a comparable group of Latina patients was interviewed, potential practical, psychologic, and cultural barriers to optimal care were identified. CONCLUSIONS: The results from this exploratory study support the need for further studies to document the pattern of adherence to radiotherapy in the rest of the country among this minority population. The results suggest that an intervention to improve information and adherence to radiation therapy may be necessary to assure Latinas a chance for rates of cure comparable with the national standards.

Biologically selected recombinants between feline leukemia virus (FeLV) subgroup A and an endogenous FeLV element.

In efforts to elucidate the proximal leukemogens that might be produced during a feline leukemia virus (FeLV) infection of cats, homologous recombinations between molecularly cloned exogenous and endogenous FeLV proviruses of known sequences were examined in cell cultures in vitro. A plasmid containing an infectious member of the most commonly occurring FeLV subgroup (FeLV subgroup A or FeLV-A) was coexpressed with noninfectious constructs containing the envelope (env) gene of an endogenously inherited FeLV-like feline genomic element in transfected feline fibroblasts. The viruses generated were selected for their ability to propagate in human cells which are resistant to infection by the parental ecotropic FeLV-A or the noninfectious endogenous constructs. An analysis of the recombinants thus derived identified a limited number of sites in the env gene which were preferentially utilized in the generation of recombinant FeLVs under the selection conditions used. These sites were clustered in the surface glycoprotein (SU) moiety of the env gene, and it appeared that most, but not all, of the SU gene product of FeLV-A, beginning from the N-terminus, can be replaced by sequences from an endogenous element, still allowing the virus to be biologically viable. In fact, these substitutions in the env gene expanded infectivity of the parental FeLV-A from ecotropic to polytropic cell tropism. Additionally, substitutions in the SU region yielded many recombinants in which a primary neutralizing pentapeptide epitope of FeLV-A was altered because of its variance in the endogenous element. In several of the recombinants, this sequence was also found to be frequently mutated. Consistent with the changes identified in this antibody-binding domain, the recombinant viruses were only weakly inhibited by a monoclonal antibody directed against this epitope, while FeLV-A was highly sensitive to neutralization.

Treatment of cervical carcinoma employing a template for transperineal interstitial Ir192 brachytherapy.

The development of a template technique at this institution for transperineal interstitial-intracavitary brachytherapy employing Ir192 wire has previously been reported. In this paper we report the results of radiation treatment of 84 women with fresh, primary squamous carcinoma of the cervix admitted to the Los Angeles County--University of Southern California Medical Center from April, 1975 to September, 1979 who received at least one transperineal template implant as part of their initial treatment. The 75 evaluable patients were followed 3 to 60 months, with a median of 17 months. Recurrence rates in the pelvic treatment field by clinical (FIGO) stage grouping were 35.7% (5/14) Stage IB;0% (0/8) Stage IIA; 20% (5/25) Stage IIB; 46.2% (12/26) Stage III; and 0% (0/2) Stage IVA. The overall failure rate within the treatment field was 29.3% (22/75). The non-tumor associated rectovaginal and vesicovaginal fistula rate was 14.3% (2/14) in Stage IB; 0% (0/8) in Stage IIA; 16.0% (4/25) in Stage IIB; 15.4% (4/26) in Stage III; and 0% (0/2) in Stage IVA. The non-tumor associated fistula rate for all stages was 13.3% (10/75). Severe or grade III nonfistulous, delayed adverse effects (proctosigmoiditis, cystitis, vault necrosis) occurred in an additional 6 patients. Thus, 21.3% (16/75) of all evaluable patients experienced severe adverse radiation effects during the follow-up period. Pre-radiation staging laparotomy was performed on 31 patients. It had no obvious effect on the pattern or rate of radiation complications. The role of the interstitial-intracavitary template in the treatment of primary cervical carcinoma is discussed.

Reversion of Kirsten sarcoma virus transformed human cells: elimination of the sarcoma virus nucleotide sequences.

The virus-specific nucleotide sequences in the RNA and DNA of a Kirsten mouse sarcoma virus (Ki-MSV)-transformed non-producer human osteosarcoma cell clone and two subclones of these cells that reverted to a normal phenotype have been analysed by hybridization of sarcoma virus-specific complementary DNA (cDNA) to cellular RNA or DNA. Whereas the transformed clone had acquired de novo Ki-MSV sequences in the RNA and DNA of the cells, both the revertant cell lines seemed to have lost most or all of this information from the cellular nucleic acids. The DNA from the revertant cells lacked the sequences represented either in the Ki-MSV-specific cDNA or in the total cDNA of the leukaemia-sarcoma virus complex. Thus, the reversion of the virus-transformed human cells to normal morphology is associated with the loss of most or all of the proviral sequences from the cellular DNA.

C-type RNA virus from hamster cells transformed in vitro by 1-B-D-arabinofuranosylcytosine.

Evidence of type-C RNA viral activity in fetal hamster cells transformed in vitro by 1-B-D-arabinofuranosylcytosine (ara-C) after at least one in vivo passage is described. The virus possesses properties typical of other type-C RNA viruses, such as: a) morphology as determined with the electron microscope, b) presence of 70S RNA, c) enhanced expression following treatment with halogenated pyrimidines, d) group specific antigens of hamster type, and e) a buoyant density of 1.15 g per cm3. However, the virus particles are deficient in RNA-dependent DNA polymerase activity under conditions that easily detect Rauscher Leukemia virus and will infect neither hamster, rat, mouse, human nor rabbit cells. The possible role of this virus in chemical carcinogenesis of cultured hamster fetal cells is discussed.

Suppression of infectious murine leukemia virus in wild mice (Mus musculus) by passive immunization.

Passive immunization with heterologous antivirus antiserum beginning at birth successfully suppressed infectious murine leukemia virus expression in Lake Casitas wild mice (Musmusculus) at 5-7 weeks of age.

Transformation of cultured rat adrenocortical cells by Kirsten murine sarcoma virus (Ki-MSV).

Two-week-old primary cultures of normal adult rat adrenal cortex were exposed to Kirsten murine sarcoma virus (KiMSV). Within a week, the adrenal cells, which are normally fusiform and aligned in parallel, became pleomorphic and piled up extensively. Saturation density increased from 5-10 x 10(4) to 5-10 x 10(5) cells/cm2, population doubling time during exponential growth decreased from 36-40 to 16h, acid production increased and the growth rate became independent of a reduction in serum concentration from 10% to 1%. Inoculation of 2 x 10(6) of these transformed cells into immuno-depressed rats produced rapidly growing tumors within 1 week. Histologically, the tumors were pleomorphic carcinomas with areas ranging from anaplasia to near-normal, highly differentiated adrenocortical tissue. In addition to histologic evidence of differentiation, metabolic studies using 14C-prognenolone showed that the transformed cells were capable of 20alpha reduction and delta5,3beta dehydrogenation, both characteristic of normal steroid-secreting tissues. The transformed adrenocortical cells produced infectious C-type virus as indicated by electron microscopy, 3H-uridine incorporation, and focus formation in NRK (normal rat kidney) cultures. The neutralization pattern of this virus resembled that of authentic Ki-MSV. The transformation of adrenocortical cells by K-MSV demonstrates the capacity of this agent to induce carcinomas in differentiated cells after short-term culture, and widens the range of tissues known to be susceptible to K-MSV to include a secretory epithelium of mesodermal origin.

Inefficient humoral immune response of lymphoma-prone wild mice to persistent leukemia virus infection.

Adult wild mice (LC) from a natural colony with a high incidence of spontaneous lymphomas had free infectious virus in their seara (average 10(3.5) infectious units/ml) and parenchymal organs (average 10(5.2) infectious units/g tissue). They did not have detectable levels of free virus-specific antibodies that could be demonstrated by virus neutralization or immunofluorescence at higher than a 1:10 dilution. Only 5 of 28 animals had free antibodies detectable by radioimmunoprecipitation assay, and tissues of 4 mice also had nondetectable levels of virus determined by infectivity assay. Formalized vaccine from the indigenous virus did not induce production of virus-neutralizing antibodies or protect against naturally occurring disease. The animals with persistent leukemia virus infection, however, elicited good humoral immune responses to virus-unrelated antigen.

Assay for type C virus in mouse sera based on particulate reverse transcriptase activity.

Assay of particulate reverse transcriptase activity in the sera from feral mice naturally infected with type C virus provides a sensitive and rapid procedure for the determination of in vivo virus infection. The results compare well with assays for infectious virus and with complement fixation or competitive radio-immunoassays for the p30 internal antigen of the virus.

Type C virus expression in lymphoma-paralysis-prone wild mice.

Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infectious type C virus in the liver, spleen, and thymus within the first few weeks of life. By young adulthood about 80% of LC mice (including their genital tissues) were infected. Virus isolates from these mice cause lymphoma and lower limb paralysis under both natural and experimental conditions. Mice destined to develop paralysis showed higher levels of serum gs antigen early in life, whereas mice destined to develop lymphoma or remain free of these diseases could not be distinguished by this test. The individual variation in virus expression suggested that differences in virus type or in the immune or other host defense mechanisms greatly influenced susceptibility or resistance to indigenous type C virus-caused disease in LC wild mice.