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1.
Ann Surg Oncol ; 15(4): 1048-55, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18214616

ABSTRACT

BACKGROUND: The possible association between ovulation-inducing drugs and breast cancer development has been debated. Our aim was to evaluate the incidence of breast cancer in a cohort of women exposed to in vitro fertilization (IVF). METHODS: A retrospective cohort analysis was performed by linkage of the computerized database of all women treated at the IVF Unit at Assaf Harofeh Medical Center between 1986 and 2003, and the Israeli National Cancer Registry. The standardized incidence ratio (SIR) was computed as the ratio between the observed number of breast cancer cases and the expected cases, adjusted for age and continent of birth, in the general population. Tumor characteristics of the IVF patients were studied by reviewing original medical records. RESULTS: 35 breast carcinomas were diagnosed among 3,375 IVF-treated women, compared to 24.8 cases expected (SIR = 1.4; 95% CI 0.98-1.96). Age >or=40 years at IVF treatment (SIR = 1.9; 95% CI 0.97-3.30), hormonal infertility (SIR = 3.1; 95% CI 0.99-7.22), and >or=4 IVF cycles (SIR = 2.0; 95% CI 1.15-3.27) were found to be risk factors to develop breast cancer compared to the general population. Multivariate analysis revealed that women who underwent >or=4 IVF cycles compared to those with one to three cycles were at risk to develop breast cancer, although not significantly (SIR = 1.9; 95% CI 0.95-3.81). Of IVF-treated women 85% had ER(+) tumors and 29% had positive family history. CONCLUSIONS: A possible association between IVF therapy and breast cancer development was demonstrated, especially in women >or=40 years of age. These preliminary findings need to be replicated in other cohort studies.


Subject(s)
Breast Neoplasms/epidemiology , Fertility Agents, Female/adverse effects , Fertilization in Vitro/adverse effects , Adult , Breast Neoplasms/etiology , Female , Humans , Incidence , Infertility, Female/therapy , Middle Aged , Ovulation Induction/adverse effects , Retrospective Studies
2.
Breast ; 16(1): 60-7, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17276293

ABSTRACT

The characteristics, menstrual risk factors and surgical therapy of 187 consecutive patients more than 70 years of age (mean: 75.9) were investigated and compared with those of 609 patients less than 70 years of age (mean: 53.9). There was no difference in stage, size, state of axillary nodes, grade, histological types, Ki-67, vascular invasion, estrogen receptor rate, and HER-2/neu (+) rate. Positive progesterone receptor rate was higher in older patients (54.7% vs. 63.1%). Tumors were larger (p=0.01) and their stage higher (p=0.014) in patients more than 80 years of age. All menstrual risk factors were similar in the two groups. Positive familial history was more frequent in patients <60 years. Significantly more young patients used hormone replacement therapy (HRT) (21.8 vs. 8.6%). Older patients underwent less breast-conserving surgery (36.1 vs. 55.1%), and less axillary lymph node dissection (ALND) (69.7 vs. 84.9%). We conclude that breast cancer characteristics and menstrual risk factors are similar in the two age groups.


Subject(s)
Breast Neoplasms/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Breast Neoplasms/surgery , Estrogen Replacement Therapy/statistics & numerical data , Humans , Israel/epidemiology , Lymph Node Excision/statistics & numerical data , Mastectomy, Segmental/statistics & numerical data , Menarche , Middle Aged , Retrospective Studies , Risk Factors
3.
Br J Cancer ; 90(4): 773-80, 2004 Feb 23.
Article in English | MEDLINE | ID: mdl-14970852

ABSTRACT

This paper is a report of response rate (RR) and survival of 34 metastatic melanoma patients who received a dinitrophenyl (DNP)-modified autologous melanoma cell vaccine. In all, 27 patients started the vaccine as a primary treatment for metastatic melanoma and seven started it as an adjuvant, with no evidence of disease at the time, but had developed new metastases. Interleukin-2 (IL-2) was administered in 24 out of the 34 patients: 19 who progressed on vaccine alone and five who had the combination from start. Interleukin-2 was administered in the intravenous, bolus high-dose regimen (seven patients) or as subcutaneous (s.c.) low-dose treatment (17). Overall response for the entire group was 35% (12 patients out of 34), 12% having a complete response (CR) and 23% a partial response (PR). However, only two patients had tumour responses while on the vaccine alone, whereas the other 10 demonstrated objective tumour regression following the combination with IL-2 (two CR, eight PR), lasting for a median duration of 6 months (range 3-50 months). Of the 12 responding patients, 11 attained strong skin reactivity to the s.c. injection of irradiated, unmodified autologous melanoma cells. None of the patients with a negative reactivity experienced any tumour response. Patients with positive skin reactions survived longer (median survival - 54 months). The results suggest enhanced RRs to the combination of IL-2 and autologous melanoma vaccine. Skin reactivity to unmodified autologous melanoma cells may be a predictor of response and improved survival, and therefore a criterion for further pursuing of immunotherapeutic strategies.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cancer Vaccines/immunology , Interleukin-2/pharmacology , Interleukin-2/therapeutic use , Melanoma/drug therapy , Melanoma/immunology , Skin Neoplasms/drug therapy , Skin Neoplasms/immunology , Adolescent , Adult , Aged , Child , Combined Modality Therapy , Dinitrobenzenes , Disease Progression , Female , Humans , Male , Melanoma/pathology , Middle Aged , Neoplasm Metastasis , Skin Neoplasms/pathology , Survival Analysis , Treatment Outcome
4.
Histopathology ; 41(1): 30-4, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12121234

ABSTRACT

AIMS: The aim of our study was to investigate the clinical, pathological and immunohistochemical features of breast hamartomas, in order to obtain a detailed profile of this somewhat uncommon lesion. METHODS AND RESULTS: This study presents a clinical, pathological and immunohistochemical analysis of 24 breast hamartomas. Four cases of fibrocystic breast changes were used as a control group. The immunohistochemical panel induced oestrogen (ER) and progesterone (PR) receptors, c-erbB-2 protein, p53, Ki67, CK-MNF116, and vimentin. The patients ranged in age from 30 to 78 years (mean 48 years). All patients presented with a palpable unilateral mass. Three patients showed two hamartomas in the same breast. Tumours ranged from 20 to 50 mm in diameter. Typical macroscopic and microscopic features were noted. Immunohistochemical studies showed ER and PR receptor positivity in epithelial cells as well as in the stromal cells in all 24 cases. No c-erbB-2 protein over-expression was noted. p53 expression was not observed. Ki67 showed 2-3% positivity in epithelial cells and not in stromal cells in most cases. CONCLUSIONS: There was no association with side, ethnic origin or dietary habits. The immunohistochemistry of hamartomas is generally similar to normal breast or fibrocystic breast tissue. Ki67 together with receptor positivity may reflect some proliferative activity and explain observed faster growth of hamartoma during pregnancy and lactation.


Subject(s)
Breast Diseases/metabolism , Breast Diseases/pathology , Hamartoma/metabolism , Hamartoma/pathology , Adult , Aged , Biomarkers , Female , Humans , Immunohistochemistry , Middle Aged , Receptors, Estrogen/biosynthesis , Receptors, Progesterone/biosynthesis
5.
Nucl Med Commun ; 22(7): 807-11, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11453054

ABSTRACT

Scintimammography using 99Tc(m)-MIBI (99Tc(m)-sestamibi) has demonstrated promising results in the detection of breast cancer. Recently scintimammography using 99Tc(m)-tetrofosmin has been suggested as a better diagnostic tool and a more convenient agent to use in this condition. In this study we compared both agents in 35 consecutive women with abnormal mammographic or physical findings. Thirty-four of them underwent MIBI scan, followed by tetrofosmin scan 2 days later (performed on all 35 women). Within 2 weeks, a pathological diagnosis was obtained either by needle or open biopsy. In both scans the uptake ratio between the lesion and the background uptake was calculated. Twenty patients who underwent tetrofosmin scan and 19 patients with MIBI scan had malignant breast tumours, while 15 women had benign lesions. The sensitivity, specificity, positive and negative predictive values and total accuracy of the MIBI scan were 89.4%, 80%, 85%, 85.7% and 85.3%, respectively; almost identical values were obtained with tetrofosmin (90%, 80%, 85.6%, 85.7% and 85.7%, respectively). The uptake ratios in the MIBI and tetrofosmin scans were 1.68 +/- 0.52 and 1.7 +/- 0.47, respectively. No differences were found between the two scintimammographies in all the parameters examined. In conclusion, MIBI and tetrofosmin breast scans are accurate and equally efficient for the detection of breast malignancies.


Subject(s)
Breast Neoplasms/diagnostic imaging , Mammography/methods , Organophosphorus Compounds , Organotechnetium Compounds , Radiopharmaceuticals , Technetium Tc 99m Sestamibi , Adult , Aged , Breast Neoplasms/pathology , Female , Humans , Middle Aged , Radionuclide Imaging
6.
Isr Med Assoc J ; 3(3): 169-73, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11303372

ABSTRACT

BACKGROUND: High dose interleukin-2 therapy, administered in bolus, is considered to be a reasonable treatment option in a selected group of patients with metastatic malignant melanoma. OBJECTIVES: To present our experience using this mode of therapy in 21 patients with metastatic melanoma. MATERIALS AND METHODS: The 21 patients in our study group comprised 13 men and 8 women with a mean age of 46 years (range 29-63). Their metastatic disease was present in all extracranial sites, dermal and sub-dermal metastases being the most common (15 patients had at least one site, in addition to other locations of metastases). Patients with intracranial disease were excluded due to the poor effectivity of IL-2 at this site. Treatment comprised a course of 2 weeks of therapy with a 1 week rest interval between. Radiological and physical evaluation was performed 6-8 weeks after the first course. If a response was achieved a second course of therapy was given. Patients received up to 14 planned doses of IL-2 in each week, 720,000 IU/kg of IL-2 per dose i.v. in 15 minutes. All treatments were given in the surgical ward, and only one patient was hospitalized in the intensive care unit. RESULTS: Of the 21 patients, one had a complete response that has lasted for 17 months and 5 patients had a partial response (range 3 months to 3 years). One patient died during treatment, and one patient who refused further treatment because of no response died a few days after completion of treatment. Prior to therapy three of the responders had received autologous vaccines with good immunological response (P = 0.115). Toxic side effects were significant, but they were treated successfully with no residual damage. CONCLUSIONS: High dose IL-2 can be administered safely in a surgical department. The response rates achieved in this series justify the use of high dose IL-2 in a selected group of patients. To improve response rates, a combination of autologous vaccines prior to high dose IL-2 may be recommended.


Subject(s)
Interleukin-2/therapeutic use , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Melanoma/pathology , Pelvic Neoplasms/secondary , Pelvic Neoplasms/therapy , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Skin Neoplasms/secondary , Skin Neoplasms/therapy , Adult , Aged , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Injections, Intravenous , Interleukin-2/immunology , Interleukin-2/pharmacology , Liver Neoplasms/diagnosis , Lung Neoplasms/diagnosis , Male , Middle Aged , Pelvic Neoplasms/diagnosis , Peritoneal Neoplasms/diagnosis , Remission Induction , Skin Neoplasms/diagnosis , Time Factors , Tomography, Emission-Computed , Tomography, X-Ray Computed , Treatment Outcome
7.
Dig Surg ; 17(5): 508-12, 2000.
Article in English | MEDLINE | ID: mdl-11124557

ABSTRACT

BACKGROUND: Cecal diverticulitis is frequently indistinguishable from acute appendicitis preoperatively and is sometimes mistaken for carcinoma at laparotomy. The surgeon must be aware of the possibility of diverticulitis of the cecum in the operating room and choose the appropriate treatment. PURPOSE: Because there is no universal therapeutic approach to these patients, we decided to assess the presenting symptoms, clinical findings, preoperative diagnosis, operative findings determining the proper management of these patients. METHODS: A retrospective chart review of 13 patients with pathologically confirmed cecal diverticulitis, who underwent surgery in our department from 1984 to 1998, was undertaken. RESULTS: The mean age of patients was 43.5 years. Right lower quadrant pain and local tenderness were the only clinical findings in 92.3%, with preoperative diagnosis of acute appendicitis in 84.6% of patients. The operative finding in most cases was inflammatory mass of the cecum; in 6 cases it was indistinguishable from perforated cecal carcinoma. Six patients underwent right hemicolectomy, 5 had ileocecectomy, 1 patient was treated by tube cecostomy, and 1 had diverticulectomy. There were three minor postoperative complications: pneumonia, wound infection and lower limb superficial thrombophlebitis. CONCLUSIONS: Cecal diverticulitis needs a high index of suspicion for achieving a preoperative diagnosis. We suggest that the operative therapy should be ileocecectomy. The surgical specimen should be examined during surgery and only if carcinoma is found should the patient have a formal colectomy.


Subject(s)
Cecal Diseases/diagnosis , Diverticulitis, Colonic/diagnosis , Adult , Aged , Cecal Diseases/surgery , Digestive System Surgical Procedures , Diverticulitis, Colonic/surgery , Female , Humans , Male , Middle Aged , Retrospective Studies
8.
Harefuah ; 138(11): 932-5, 1007, 2000 Jun 01.
Article in Hebrew | MEDLINE | ID: mdl-10979402

ABSTRACT

Breast cancer can be detected by scintimammography using Tc-99m sestamibi (MIBI). The method is highly accurate, sensitive and specific. Histologically, most of the tumors have been adenocarcinomas. We present 2 women with rare breast tumors, primary squamous cell carcinoma and malignant phyllodes tumor. In both, mammography and cytological biopsy were not diagnostic, but MIBI scintimammography demonstrated focal uptake in the diseased breast.


Subject(s)
Breast Neoplasms/diagnostic imaging , Carcinoma, Squamous Cell/diagnostic imaging , Phyllodes Tumor/diagnostic imaging , Breast Neoplasms/surgery , Carcinoma, Squamous Cell/surgery , Female , Humans , Mammography , Middle Aged , Phyllodes Tumor/surgery , Radionuclide Imaging , Reproducibility of Results , Sensitivity and Specificity
9.
Nucl Med Commun ; 20(6): 511-6, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10451862

ABSTRACT

We evaluated the efficacy of 99Tcm-sestamibi (MIBI) scintimammography for the detection of breast cancer in 332 patients. Two hundred and seven scans were confirmed by histological or cytological results; the other patients were examined because they belonged to high-risk groups or had dense fibroglandular breasts. Of 207 patients with histological confirmation, 112 positive studies were obtained: 86 true-positive and 26 false-positive. Scintimammography was negative in 95 patients: 88 true-negative and seven false-negative. Six of seven false-negative results were obtained in patients with impalpable tumours. The sensitivity, specificity, positive and negative predictive values were 92.5%, 77.2%, 76.8% and 92.6% respectively. The overall accuracy was 84.1%. To identify false-positive results, the count ratio of the target lesion to the contralateral normal area on 38 true-positive scans and in 26 false-positive examinations was calculated from the region of interest drawn on the 99Tcm-MIBI scan (L/N ratio). A significantly higher ratio was found for the true-positive scans (1.583 +/- 0.501 vs 1.246 +/- 0.213; P = 0.0002). In conclusion, 99Tcm-MIBI scintimammography is a sensitive and accurate method for the detection of breast malignancies.


Subject(s)
Breast Neoplasms/diagnostic imaging , Radiopharmaceuticals , Technetium Tc 99m Sestamibi , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , False Negative Reactions , False Positive Reactions , Female , Humans , Middle Aged , Predictive Value of Tests , Radionuclide Imaging , Sensitivity and Specificity
10.
Harefuah ; 132(2): 86-8, 151, 1997 Jan 15.
Article in Hebrew | MEDLINE | ID: mdl-9119306

ABSTRACT

We reviewed the records of 22 patients hospitalized at onset or first presentation of Crohn's disease after age 50. There were 12 females and 10 males, and the mean age was 64.5 years. The most common presenting symptoms were: abdominal pain, fever, diarrhea and weight loss. The disease was located in the small bowel in 14, in the ileo-colic region in 3 and in the colon in 5. The median interval from onset of symptoms until diagnosis was 42 months. 12 (54%) underwent surgery. All 5 patients with colonic disease were operated. 6 patients underwent small bowel resections, mostly terminal ileum, while 1 had resection of both terminal ileum and left colon. The recurrence rate was 70% in the medically treated and 50% in those operated. 1 patient died after surgery for Crohn's disease (4.5%), and 3 others died of unrelated causes. Compared to younger patients, the symptomatology, clinical course, need for and response to surgery, and its complications, did not differ in these older patients, but the recurrence rate seemed to be higher.


Subject(s)
Crohn Disease , Aged , Colitis/surgery , Crohn Disease/diagnosis , Crohn Disease/physiopathology , Crohn Disease/surgery , Female , Humans , Ileitis/surgery , Male , Middle Aged , Recurrence
11.
J Surg Res ; 58(2): 218-26, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7861776

ABSTRACT

Interleukin-12 (IL-12) is a cytokine with a wide variety of immunoregulatory activities. These include stimulation of interferon-gamma production, cytolytic activity of natural killer (NK) cells and T-cell subsets, the development of cellular immunity, and induction of maturation of Th1 cells. IL-12 also has potent anti-tumor activity in vivo. In the present study the possibility of enhanced anti-tumor activity was examined using a combination of local IL-12 by cytokine gene therapy at the tumor site, combined with systemic or local IL-2 delivery. NIH 3T3 fibroblasts transfected with the genes for both subunits of IL-12, p35 and p40, were used as the source of IL-12 therapy producing 240 HLRU/10(6) cells/48 hr. In the first part of the study the effect of different regimens of systemic IL-2 delivery with local IL-12 administration on the size and growth rate of subcutaneous MCA-105 murine sarcoma was examined. Local IL-12 alone reduced the sizes of tumors after 32 days from 163 to 26.8 mm2 (P < 0.002). Adding the longer-acting polyethylene-glycol-modified IL-2 (PEG IL-2; 30,000 IU) for 5 days prevented the development of tumors in all treated mice compared to 1/3 mice treated with PEG IL-2 alone and 3/6 mice with IL-12, but this was a highly toxic therapy and most of the animals died. Administration of 60,000 IU of IL-2 on Days 1-5 postinoculation of tumor, delivered with IL-12 gene therapy, reduced the tumor growth rate compared to animals treated with IL-2 alone (P < 0.02) or IL-12 (0.1).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Genetic Therapy , Interleukin-12/genetics , Interleukin-2/administration & dosage , Neoplasms, Experimental/therapy , 3T3 Cells , Animals , Female , Interferon-gamma/physiology , Interleukin-12/administration & dosage , Mice , Mice, Inbred C57BL , Transfection , Tumor Cells, Cultured
12.
JPEN J Parenter Enteral Nutr ; 19(1): 80-2, 1995.
Article in English | MEDLINE | ID: mdl-7658606

ABSTRACT

BACKGROUND: In previous studies, we demonstrated the overgrowth of gram-negative bacteria in the gut and an enhanced release of tumor necrosis factor (TNF) by peritoneal macrophages, suggesting that endotoxin, TNF, or both, may act as hepatotoxins to produce hepatic steatosis during total parenteral nutrition (TPN) and bowel rest. The present study attempts to better define the role of each of these two mediators. The first part examines the LD50 for various doses of endotoxin in TPN-treated rats compared with free-feeding and free-feeding saline-infused rats. In the second part we repeatedly administered anti-TNF monoclonal antibodies to rats subjected to TPN and bowel rest. METHODS: In the first set of experiments, 87 male Sabra rats were randomized into three groups: free-feeding, infused with normal saline, and infused with TPN. On day 7 of the experiment, all rats received an IV injection of endotoxin at various doses (1.5, 2.5, 5.0, 7.5, and 10 mg/kg). The LD50 in the three groups and at the various doses of lipopolysaccharide tested was determined at 24 hours postinjection. In the second set of experiments, 38 male Sabra rats were randomized into three groups: infused with normal saline and fed rat food ad libitum, infused with TPN, and infused with TPN but also receiving monoclonal antibodies against TNF. RESULTS: Lower endotoxin doses were required to achieve LD50 in the two IV-infused groups (2.5 to 5.0 mg/kg) compared with the free-feeding group (7.5 mg/kg) (p < .03). These findings suggest a moderate increase in susceptibility to the lethal effect of endotoxin in IV-treated rats. The total hepatic fat and triglyceride levels, which were markedly increased in TPN rats, were significantly reduced by using anti-TNF antibodies. Enhanced TNF production by peritoneal macrophages during TPN was completely eliminated by anti-TNF antibodies, probably the result of suppressed TNF production. CONCLUSIONS: The continuous translocation of endotoxin from gram-negative bacterial overgrowth in the gut during TPN and bowel rest results in enhanced release of TNF by macrophages. TNF causes hepatic dysfunction, portrayed in the present experimental model as hepatic steatosis. TPN-induced hepatic steatosis was significantly reduced by the administration of monoclonal antibodies against TNF-alpha.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Fatty Liver/prevention & control , Parenteral Nutrition, Total/adverse effects , Tumor Necrosis Factor-alpha/immunology , Animals , Cholesterol/metabolism , Fatty Liver/etiology , Lipid Metabolism , Liver/metabolism , Macrophages, Peritoneal/metabolism , Male , Rats , Triglycerides/metabolism , Tumor Necrosis Factor-alpha/physiology
13.
Nutrition ; 10(2): 151-4, 1994.
Article in English | MEDLINE | ID: mdl-8025369

ABSTRACT

We hypothesize that catheter-related sepsis with Candida during total parenteral nutrition (TPN) is caused by Candida translocation from the gut. Fifty male Sabra rats weighing 330 +/- 40 g were randomized into four groups and put into metabolic cages: group 1 (n = 16), nonoperated free-feeding controls; group 2 (n = 10), infused with normal saline and free feeding; group 3 (n = 14), infused with TPN solution for a total of 36 kcal and 1.5 g g protein.100 g-1 body wt.day-1;group 4 (n = 10), same TPN regimen as group 3 but also receiving oral and intravenous antibiotics. On day 7, all animals received 1.5 x 10(10) viable Candida albicans CBS 562 cells by gavage, and 24 h later, the number of Candida colony-forming units in blood, mesenteric lymph nodes, and kidneys was determined. No growth of Candida was detected in group 1 or group 2. Positive Candida cultures were found in the blood, mesenteric lymph nodes, and kidneys of groups 3 and 4, although levels reached statistical significance only for mesenteric lymph nodes in group 3. Because Candida growth occurred exclusively in groups receiving TPN and bowel rest, we conclude that altered gut-barrier function to Candida occurs during TPN and speculate that Candida sepsis during TPN might be the result of Candida translocation from the gut due to the combination of high-density Candida colonization and favorable local conditions in the gut induced by TPN and bowel rest.


Subject(s)
Candidiasis , Fungemia/etiology , Intestines/microbiology , Parenteral Nutrition, Total/adverse effects , Animals , Blood/microbiology , Candida albicans/isolation & purification , Kidney/microbiology , Lymph Nodes/microbiology , Male , Mesentery , Rats
14.
Cancer Res ; 54(1): 182-9, 1994 Jan 01.
Article in English | MEDLINE | ID: mdl-7903204

ABSTRACT

Interleukin 12 (IL-12), a disulfide-linked heterodimeric cytokine produced primarily by macrophages, is composed of light (p35) and heavy (p40) chains. It binds to a receptor on T-cells and natural killer cells, promoting the induction of primarily a TH1 response in vitro and in vivo. To determine whether paracrine IL-12 secretion can alter tumor cell growth or promote antitumor immunity, we have developed a delivery system using genetically engineered fibroblasts in murine tumor models. NIH3T3 cells were stably transfected to express 100-240 units/10(6) cells/48 h of IL-12 using expression plasmids carrying both the murine p35 and p40 genes of murine IL-12. The effects of paracrine secretion of IL-12 on tumor establishment and vaccination models were examined using the poorly immunogenic murine melanoma cell line (BL-6) in C57BL/6 mice. To determine the effects of IL-12 on tumor formation, nonirradiated BL-6 cells were inoculated s.c. into C57BL/6 mice admixed with NIH3T3 cells transfected with both subunits of mIL-12 (3T3-IL-12) or with cells transfected with only the neomycin phosphotransferase gene (3T3-Neo). Compared to mice given injections of BL-6 alone, the day of emergence of detectable tumors was significantly delayed in mice given injections of BL-6 admixed with 3T3-IL-12, but not in mice with BL-6 admixed with 3T3-Neo. Effectiveness in this system was related to the amount of IL-12 expressed by the 3T3-IL-12. To determine the ability of locally secreted IL-12 at the tumor site to induce antitumor immunity, 10(6) irradiated tumor cells mixed with 3T3-IL-12 or 3T3-Neo were injected as a vaccine, and the response to a tumor challenge was subsequently examined. With a tumor challenge of less than 1 x 10(5) nonirradiated BL-6 cells, significant delay of establishment of tumor was noted with a relatively small amount of IL-12 secretion (1.2 units/5 x 10(5) cells/48 h). Larger amounts of secreted IL-12 provided no additional therapeutic benefit. Histological examination of tumor inoculum with 3T3-IL-12 secreting a high level of IL-12 showed peritumoral accumulation of macrophages, a characteristic capsule around the tumor composed of palisades of fibroblasts, and decreased numbers of CD4+ cells in the tumor. These results suggest that local delivery of IL-12 inhibits tumor growth in a dose dependent manner but leads to the development of an antitumor immune response when IL-12 is expressed at the tumor site at the relatively small amount indicated above.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Fibroblasts/metabolism , Interleukins/metabolism , Melanoma/prevention & control , Phosphotransferases (Alcohol Group Acceptor)/genetics , RNA, Messenger/metabolism , 3T3 Cells , Animals , Base Sequence , Cell Division/immunology , Cell Line , Immunotherapy , Interleukin-12 , Interleukins/genetics , Kanamycin Kinase , Melanoma/immunology , Melanoma/pathology , Mice , Molecular Sequence Data , Polymerase Chain Reaction , Transfection
15.
Urol Int ; 52(1): 38-40, 1994.
Article in English | MEDLINE | ID: mdl-8140678

ABSTRACT

Spontaneous rupture of the urinary bladder is a rare entity. This is, in part, the cause for the low rate of correct preoperative diagnosis, the high rate of delayed diagnosis, morbidity and mortality. We report a case of spontaneous rupture of the urinary bladder in an adult patient, complicated by extensive fascitis of the abdominal wall. The stormy course and long hospitalization in the case described are characteristic of patients with spontaneous bladder rupture and warrant a high index of suspicion in order to achieve an early diagnosis.


Subject(s)
Abdominal Muscles/pathology , Fasciitis/etiology , Urinary Bladder Diseases/complications , Aged , Fasciitis/pathology , Humans , Male , Rupture, Spontaneous , Urinary Bladder Diseases/diagnosis
16.
Harefuah ; 124(7): 410-1, 455, 1993 Apr 01.
Article in Hebrew | MEDLINE | ID: mdl-8330786

ABSTRACT

Spontaneous rupture of the spleen is rare Although over 100 cases have been reported, only a few were of true spontaneous rupture. Most cases were associated with diseases which directly involved the spleen. We report a 53-year-old woman with facial erysipelas and true spontaneous rupture of the spleen.


Subject(s)
Erysipelas/complications , Facial Dermatoses/complications , Splenic Rupture/complications , Female , Humans , Middle Aged , Rupture, Spontaneous
17.
JPEN J Parenter Enteral Nutr ; 16(6): 529-32, 1992.
Article in English | MEDLINE | ID: mdl-1494209

ABSTRACT

Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements. Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production. In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN-associated hepatic steatosis. Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels. Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group. The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin. We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN.


Subject(s)
Fatty Liver/prevention & control , Gram-Negative Bacteria/drug effects , Lipopolysaccharides/antagonists & inhibitors , Parenteral Nutrition, Total/adverse effects , Polymyxin B/pharmacology , Administration, Oral , Animals , Fatty Liver/etiology , Fatty Liver/microbiology , Gram-Negative Bacteria/growth & development , Injections, Intravenous , Male , Polymyxin B/administration & dosage , Rats , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/drug effects
18.
Harefuah ; 123(1-2): 14-6, 71, 1992 Jul.
Article in Hebrew | MEDLINE | ID: mdl-1324209

ABSTRACT

A biofragmentable anastomosis ring has recently been developed and is used in end-to-end intestinal anastomosis. It is composed of 2 circular polyglycolic acid (Dexon) components which are interdigitated to form a sutureless anastomosis. We used it in an ileo-ileal and 2 ileo-colic end-to-end anastomoses in 3 patients with Crohn's disease in the past 6 months. Postoperative recovery of bowel function and oral feeding were comparable to that in patients after conventional anastomoses with sutures or staplers. Experience accumulated in 2 large multicentric comparative studies proved that the ring is a safe, fast and effective method for bowel anastomosis. We found it to be safe even in Crohn's disease.


Subject(s)
Crohn Disease/surgery , Intestines/surgery , Anastomosis, Surgical/instrumentation , Anastomosis, Surgical/methods , Biodegradation, Environmental , Colon/surgery , Humans , Ileum/surgery , Polyglycolic Acid
19.
Eur J Surg ; 158(3): 191-3, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1356462

ABSTRACT

Giant cell arteritis and polyarteritis nodosa are systemic diseases which rarely involve the breasts. Two cases are reported in which breast masses, clinically suspected to be malignant, were found to be isolated vasculitis--bilateral giant cell mammary arteritis in a 67-year-old woman and isolated mammary polyarteritis nodosa in a 45-year-old woman. Vasculitis should be considered in the differential diagnosis of breast masses.


Subject(s)
Breast Diseases/pathology , Breast Neoplasms/pathology , Giant Cell Arteritis/pathology , Polyarteritis Nodosa/pathology , Aged , Breast/pathology , Diagnosis, Differential , Female , Humans , Mammary Arteries/pathology , Middle Aged
20.
J Surg Res ; 51(2): 106-12, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1907698

ABSTRACT

Hepatic complications are common in patients receiving total parental nutrition (TPN) and who have no underlying liver disease. In the present study we examined the hypothesis that endotoxin (LPS) or possibly TNF derived from the overgrowth of intestinal gram-negative bacteria is responsible for TPN-associated hepatic steatosis, and that bowel decontamination and specific anti-LPS activity of polymyxin B will reduce fatty infiltration of the liver during TPN. Forty-five male Sabra rats underwent jugular vein cannulation, were placed in metabolic cages, and were randomized into five groups. Group I was continuously infused with normal saline and allowed food ad lib, while group II-V were continuously infused with a TPN formula containing 4.25% amino acids and 25% dextrose for a total of 36 calories and 3.0 g protein per 100 g body weight/day. In addition, groups III-IV were also treated by oral polymyxin B while Groups IV and V received a combination of neomycin, metronidazole, and vancomycin (NMV). Thus, Group III received polymyxin B, Group IV received both polymyxin B and NMV, while Group V received NMV only. On Days 7-8 of the study, all animals were sacrificed and spontaneous production of TNF by peritoneal macrophages, bacterial translocation to mesenteric lymph nodes, culture of the cecum, and fat, triglyceride, and cholesterol contents of the liver were determined. All groups infused with TPN exhibited higher levels of total fat, triglycerides, and cholesterol compared to the free feeding control group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Cecum/microbiology , Fatty Liver/etiology , Parenteral Nutrition, Total/adverse effects , Polymyxin B/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Adipose Tissue/pathology , Animals , Cecum/metabolism , Cholesterol/metabolism , Colony Count, Microbial , Liver/pathology , Male , Mice , Mice, Inbred BALB C , Rats , Rats, Inbred Strains , Triglycerides/metabolism
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