Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi-institutional study.

OBJECTIVE: To assess the efficacy and morbidity and mortality of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (EOC). DESIGN: A retrospective study conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs). Setting Four Italian centres specializing in locoregional treatment of PSM. POPULATION: Patients with recurrent EOC. METHODS: Fifty-six patients underwent 57 combined procedures. CRS was performed using peritonectomy procedures and HIPEC using the closed-abdomen technique with cisplatin and doxorubicin or cisplatin and mitomycin-C. MAIN OUTCOME MEASURES: Overall survival (OS), progression-free survival (PFS), morbidity and mortality rates. RESULTS: The median age of the patients was 55.2 years (range 30-75 years). The median peritoneal cancer index was 15.2 (range 4-30). Forty-seven patients had microscopic residual disease (completeness of cytoreduction, CC-0), seven had residual disease ≤2.5 mm (CC-1) and one had residual disease >2.5 mm (CC>2). Major complications occurred in 15 patients (26.3%), and procedure-related mortality occurred in three patients (5.3%). The median follow-up time was 23.1 months. The median OS and PFS were 25.7 (95% CI 20.3-31.0) and 10.8 (95% CI 5.4-16.2) months, respectively. The 5-year OS and PFS were 23% and 7%, respectively. Independent prognostic factors affecting OS according to the multivariate analysis were Eastern Cooperative Oncology Group performance status, preoperative serum albumin, and completeness of cytoreduction. CONCLUSIONS: Patients with recurrent EOC treated with CRS and HIPEC showed promising results in terms of outcome. The combined treatment strategy could benefit subsets of patients wider than that defined for conventional secondary debulking surgery without HIPEC. These data warrant further evaluation in randomised clinical trials.

Model-oriented review and multi-body simulation of the ossicular chain of the human middle ear.

The ossicular chain of the human middle ear has a key role in sound conduction since it transfers vibrations from the tympanic membrane to the cochlea, connecting the outer and the inner part of the hearing organ. This study reports firstly a description of the main anatomical features of the middle ear to introduce a detailed survey of its biomechanics, focused on model development, with a collection of geometric, inertial and mechanical/material parameters. The joint issues are particularly discussed from the perspective of developing a model of the middle ear both explanatory and predictive. Such a survey underlines the remarkable dispersion of data, due also to the lack of a standardization of the experimental techniques and conditions. Subsequently, a 3D multi-body model of the ossicular chain and other structures of the middle ear is described. Such an approach is justified as the ossicles were proven to behave as rigid bodies in the human hearing range and was preferred to the more widely used finite element one as it simplifies the model development and improves joint modeling. The displacement of the umbo (a reference point of the tympanic membrane) in the 0.3-6kHz frequency range was defined as input of the model, while the stapes footplate displacement as output. A parameter identification procedure was used to find parameter values for reproducing experimental and numerical reference curves taken from the literature. This simple model might represent a valid alternative to more complex models and might provide a useful tool to simulate pathological/post-surgical/post-traumatic conditions and evaluate ossicular replacement prostheses.

Anisotropic AAA: computational comparison between four and two fiber family material models.

Abdominal aortic aneurysm (AAA) is a cardiovascular disease with high incidence among elderly population. Biomechanical computational analyses can provide fundamental insights into AAA pathogenesis and clinical management, but modeling should be sufficiently accurate. Several constitutive models of the AAA wall are present in the literature, and some of them seem to well describe the experimental behavior of the aneurysmatic human aorta. In this work we compare a two (2FF) and a four (4FF) fiber families constitutive models of the AAA wall. Both these models satisfactorily fit literature data from biaxial tests on the aneurysmatic tissue. To investigate the peculiar characteristics of these models, we considered the problem of AAA inflation, and solved it by implementing the constitutive equations in a finite element code. A 20% axial stretch was imposed to the aneurysm ends, to simulate the physiological condition. Although fitted on the same dataset, the two material models lead to considerably different outcomes. In particular, adopting a 4FF strain energy function (SEF), an increase of the circumferential stress values can be observed, while higher axial stresses are recorded for the 2FF model. These differences can be attributed to the intrinsic characteristics of the SEFs and to the effective stress field, with respect to the one experienced in biaxial experimental tests on which the fitting is based. In fact the two SEFs appear similar within the region of the stress-strain experimental data, but become different outside it, as in case of aneurysms, due to the effects of the data extrapolation process. It is suggested that experimental data should be obtained for conditions similar to those of the application for which they are intended.

Biomechanics of the tympanic membrane.

The tympanic membrane is a key component of the human auditory apparatus which is a complex biomechanical system, devoted to sound reception and perception. Over the past 30 years, various bioengineering approaches have been applied to the ear modeling and particularly to the middle part. The tympanic membrane, included in the middle ear, transfers sound waves into mechanical vibration from the ear canal into the middle ear. Changes in structure and mechanical properties of the tympanic membrane due to middle ear diseases or damages can deteriorate sound transmission. An accurate model of the tympanic membrane, which simulates the acoustic-mechanical transmission, could improve clinical surgical intervention. In this paper a detailed survey of the biomechanics and the modeling of the tympanic membrane focusing on the finite element method is conduced. Eight selected models are evaluated and compared deducing the main features and most design parameters from published models, mainly focusing on geometric, constraint and material aspects. Non-specified parameters are replaced with the most commonly employed values. Our simulation results (in terms of modal frequencies and umbo displacement), compared with published numerical and experimental results, show a good agreement even if some scattering appears to indicate the need of further investigation and experimental validation.

Allergenicity of Ascaris lumbricoides tropomyosin and IgE sensitization among asthmatic patients in a tropical environment.

BACKGROUND: Ascaris lumbricoides induces a Th2 response and specific IgE synthesis in humans. This confers antiparasite immunity but could modify the natural history of allergic diseases in the tropics, justifying the study of its allergenic composition. We analyzed the allergenic properties of Ascaris tropomyosin and the frequency of sensitization in subjects exposed to the parasite. METHODS: cDNA was obtained by reverse transcription PCR, cloned into pQE30-UA and purified as a 6× His-tagged protein. Equivalence with its natural counterpart was analyzed by cross-inhibition and liquid chromatography-tandem mass spectrometry. Specific IgE was measured by ELISA in 175 asthmatics and 170 nonasthmatics naturally exposed to the parasite and sensitized to the Ascaris extract. RESULTS: The cDNA encoded 287 residues with high sequence identity with other invertebrate tropomyosins. The 40-kDa protein was recognized by human serum and affinity-purified anti-rBlo t 10 IgE. Specific IgE to tropomyosin could represent approximately 50% of the total IgE response to the extract. Ascaris tropomyosin induced wheal and flare in skin prick tests and histamine release from basophils. Although the prevalence of IgE to Ascaris tropomyosin was higher in asthmatic patients, logistic regression analysis suggested that this result was biased by sensitization to mites. CONCLUSIONS: A. lumbricoides tropomyosin (Asc l 3) is a new allergen that binds specific IgE, induces mediator release from effector cells and is cross-reactive to mite tropomyosins. IgE reactivity to this allergen is very frequent in both asthmatic and normal subjects sensitized to Ascaris extract. The potential role of Ascaris tropomyosin in asthma pathogenesis in tropical regions should be further investigated.

Co-infection with Ascaris lumbricoides modulates protective immune responses against Giardia duodenalis in school Venezuelan rural children.

We evaluated the effect of Ascaris lumbricoides on Giardia duodenalis infection and TH1/TH2 type immune mechanisms toward this parasite in 251 rural parasitized and 70 urban non-parasitized school children. The children were classified according to light (0-5000 eggs/g faeces) or moderate (>5001-50,000 eggs/g faeces) A. lumbricoides infection. Anti G. duodenalis skin hyper-reactivity, IgE, IgG, IL-13, IFN γ, IL6 and IL-10 levels were compared among G. duodenalis infected and non-infected children according to light or moderate A. lumbricoides infection. It was found that 62% of the A. lumbricoides moderately infected children were co-infected by G. duodenalis compared to 45% of the lightly infected group. After treatment, 42% of the A. lumbricoides moderately group were infected with G. duodenalis compared to 11% of their lightly counterparts, being A. lumbricoides IL-10 levels higher (p<0.0001) in the moderately infected group. In the A. lumbricoides lightly parasitized children, G. duodenalis infection was associated to a significant increase (p<0.005) of the levels of G. duodenalis IL-13, IFN-γ, IL-6, IgE, IgG and skin test hyper reactivity. In contrast, there was no effect of G. duodenalis infection in the elevation of these parameters among the A. lumbricoides moderately parasitized group, being those levels similarly lower as those observed in the control group. Inverse correlations were found between the levels of anti G duodenalis antibodies, skin test hyper-reactivity and cytokines with the intensity of A. lumbricoides infection (p>0.0001) and A. lumbricoides IL-10 levels (p>0.0001), suggesting that co-infection with A. lumbricoides may affect both TH1 and TH2 type immunity against G. duodenalis that may play an important role in the susceptibility to the infection after chemotherapy in children from endemic areas.

Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer.

Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC). However most of the studies testing the combined approach are observational and have been conducted in inhomogeneous series so that the evidence supporting the performance of this combined treatment is still poor. Median Overall and Disease Free Survivals of up to 64 months and 57 months, respectively have been reported. Although a rate of morbidity of up to 40% has been observed in some series the CRS + HIPEC continues to gain an increased popularity. Several prospective randomized trials are ongoing using the procedure in various time points of the disease. In this review several issues such as the impact of cytoreduction and residual disease (RD) on outcomes as well as the role of HIPEC will be updated from the literature evidence. Some controversial points HIPEC related will also be discussed. Recent experiences regarding the introduction of a more aggressive surgical approach to upper abdomen to resect peritoneal carcinomatosis (PC) allowed increased rates of optimal cytoreduction and has demonstrated an apparent better outcome. This evidence associated with the positive results phase III trial testing normothermic intraperitoneal as first-line chemotherapy is guiding some investigators to propose the CRS + HIPEC in the primary setting. Several prospective phase II and III trials have recently been launched to validate the role of the combined treatment in various time points of disease natural evolution.

Infection by Ascaris lumbricoides and bronchial hyper reactivity: an outstanding association in Venezuelan school children from endemic areas.

Asthma and other respiratory diseases have increased in the last years among Venezuelan children from helminthic endemic areas where the infection by Ascaris lumbricoides has been associated to bronchial airway inflammation in parasitized individuals. The aim of this work was to investigate the possible associations between the development of bronchial hyper reactivity and the immune response against A. lumbricoides in urban and rural children. We evaluated 470 school children from rural and urban communities. Pulmonary function tests were performed and >or=20% PC(20) changes were considered as a positive diagnostic of bronchial hyper reactivity. The prevalence and intensity of A. lumbricoides infection was determined by faecal examination. Specific serum IgE levels using a modified ELISA and skin prick tests against A. lumbricoides and the common allergen Dermatophagoides pteronyssinus were done. The number of circulating lymphocyte sub populations was determined by flow cytometry analysis. In rural children, bronchial hyper reactivity was associated with increased specific levels of anti-A. lumbricoides IgE (p<0.0001) and skin test positivity for A. lumbricoides (p<0.0001). The percentage of FEV1 predictive values correlated inversely (p<0.0001) with anti-A. lumbricoides IgE levels. Elevated numbers of circulating CD3+CD4+ and CD20+CD23+ cells were found in rural children with bronchial hyper reactivity compared to their asymptomatic counterparts. They correlated positively with anti-A. lumbricoides IgE levels (p<0.005 and <0.0001, respectively). In contrast, in urban children, bronchial hyper reactivity was associated with elevated anti-D. pteronyssinus IgE levels (p=0. 0089), skin hyper reactivity towards this aero allergen (p=0.003) and to an increase in the number of CD3+CD8+ (p<0.0001). Our results suggest that the IgE response against A. lumbricoides infection may be involved in the development of bronchial hyper reactivity among rural children from endemic areas and also that improved hygienic conditions in the urban environment is associated with increased responses to airborne allergens.

Comparison of three different mesh materials in tension-free inguinal hernia repair: prolene versus Vypro versus surgisis.

Using mesh or a synthetic prosthesis during tension-free inguinal hernia repair has been shown to be safe and effective. We compared the final outcome in treating inguinal hernia in 45 patients using three different prosthetic materials: 15 patients underwent tension-free inguinal hernia repair using Prolene (polypropylene) mesh, 15 using Vypro (polyglactin and polypropylene) mesh, and 15 with Surgisis-a new bioactive material derived from porcine small intestinal submucosa. The aim of this study was to evaluate the safety and efficacy of tension-free inguinal repair using Surgisis, comparing it with conventional prosthetic materials. From January 2003 to December 2003, 45 male patients underwent Lichtenstein inguinal hernia repair. Median follow-up was 12 months, with a range of 1-16 months. Each patient underwent ultrasound evaluation of the inguinal region 1 month after surgery. All the procedures were completed under local anesthesia. There were no intraoperative complications, and all patients were discharged home the same day of surgery. No recurrent hernias and wound infections were observed in our post-operative follow-up period. Postoperative pain (visual analog score) and discomfort were lower in patients with Surgisis mesh. There was no statistically significant difference between the groups in terms of overall early and late complications; however, there was a tendency toward a higher incidence of pain and discomfort in Vypro and Prolene group. The median time to full recovery was significantly shorter in the Surgisis group. Surgisis mesh seems to be a promising new prosthetic material for hernia repair. Long-term follow-up is necessary to confirm these preliminary results.

Importance of including Blomia tropicalis in the routine diagnosis of Venezuelan patients with persistent allergic symptoms.

BACKGROUND: Blomia tropicalis is a common mite found in the house dust of many tropical countries including Venezuela. The prevalence of skin test and specific serum immunoglobulin (Ig)E reactivity to B. tropicalis in Venezuela has not been previously evaluated. METHODS: In the present study we evaluated the skin reactivity by skin prick test and specific IgE by a multiple antigen blot assay, against B. tropicalis and Dermatophagoides pteronyssinus, in a group of 115 subjects who attended the Allergy Clinic of the Institute of Biomedicine, Caracas, Venezuela, and we studied possible cross reactions between similar proteins of these two mites. RESULTS: One hundred and six patients with persistent allergic respiratory symptoms showed a positive skin prick test to at least one of the mite extracts, with the frequency of positive reactions to B. tropicalis being as high as to D. pteronyssinus. Twelve patients reacted only to D. pteronyssinus and 13 different patients only to B. tropicalis. Specific IgE to each of the mite extracts was found with similar frequency, and the results coincided with the skin test reactivity. CONCLUSIONS: The study indicated the importance of including B. tropicalis in routine diagnostic testing in tropical and sub-tropical situations.

An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells.

The specific pharmacological profile of the 19-norprogestin nomegestrol acetate (NOMAC) is, at least in part, defined by its pattern of binding affinities to the different steroid hormone receptors. In the present study, its affinity to the progesterone receptor (PgR), the androgen receptor (AR) and the estrogen receptor (ER) was re-evaluated and compared to those obtained for progesterone (P) and several progestins. The characteristics of binding to the PgR in rat uterus were determined and Ki were found to be roughly similar with 22.8 and 34.3 nM for NOMAC and P, respectively. The binding characteristics of 3H-NOMAC were also determined and compared to that of 3H-ORG2058 with Kd of 5 and 0.6 nM, respectively for rat uterus and 4 and 3 nM, respectively for human T47-D cells. Structure-affinity and -activity relationships were studied on a variety of compounds related to NOMAC in order to assess its specificity as a progestin. The effects of NOMAC on the binding of androgen to the AR were investigated, using rat ventral prostate as target model. Contrary to what was observed for MPA, the RBA of NOMAC was found to decline with time, showing anti-androgenic rather than androgenic potential, a result that was confirmed in vivo. Regarding the ER, since none of the progestins were able to compete with estrogen for binding in rat uterus as well as in Ishikawa cells, the induction of alkaline phosphatase activity (APase) was used as an estrogen-specific response. It confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT), norethisterone acetate (NETA), levonorgestrel (LNG) or norgestimate (NGM) and others. In contrast, all P and 19-norP derivatives remained inactive. Finally, to complete this overview of NOMAC at the sex steroid receptor levels, the lack of estrogenic or estrogenic-like activity was checked out in different in vitro models. Data from this study have demonstrated that NOMAC is a progestin that has greater steroid receptor selectivity compared to MPA or some other synthetic progestins. It may provide a better pharmacological profile than those progestins currently in use in HRT and OC.

Defective regulation of the protective IgE response against intestinal helminth Ascaris lumbricoides in malnourished children.

It is well established that malnutrition affects the immune response and increases the susceptibility to parasitic infection. In the present study we evaluated some aspects of the cellular and cytokine network that regulate the IgE responses, which are important components of host defence mechanisms against helminthic parasites in children infected with the intestinal helminth Ascaris lumbricoides, and with differing degrees of malnutrition. We found a defective T cell response in malnourished children, as indicated by diminished levels of circulating total (CD3+), helper (CD4+), IL-2-receptor-bearing (CD4+CD25+) and memory helper T cell responses (CD4+CD45RO+) in keeping with the decreased specific IgE levels against Ascaris lumbricoides. In contrast, the proportions of total B cells (CD20+), and those bearing the low-affinity IgE receptor (CD23+) were increased in the moderated malnourished children. Moreover, serum IL-4 levels and total IgE were also increased in these children. We suggest that malnutrition can cause an imbalance in T cell subpopulations that may lead to a defective T cell maturation and a decreased specific anti-Ascaris IgE response thus increasing the susceptibility to such infections. The high levels of total IgE observed may be related to a non-specific stimulation of the proliferation of activated B cells, probably caused by helminthic parasites and other infectious agents that are frequent in malnourished children.

Primary retrorectal adenocarcinoma: report of a case.

Primary adenocarcinomas of the retrorectal (presacral) space are uncommon and usually arise from cystic lesions developing from remnants of the embryological postanal gut (tail gut cysts) containing mucous-secreting epithelium. A singular case of a patient who presented with a retrorectal mass is described. A 70-year-old previously healthy man had a four-month history of perianal pain during defecation. Preoperative colonoscopy showed external compression of the lower rectum with normal mucosa; pelvic computed tomography demonstrated a 5.5 x 4.5 cm(2) retrorectal oval mass, originating from the posterior lower rectal wall, containing cystic components and some small calcifications. The tumor, after complete resection via transanal approach, was shown to be a very rare case of primary adenocarcinoma of the presacral space. The patient had an uneventful postoperative course and he is free from disease 4 years after surgery. Clinicopathological features and surgical treatment of this unusual tumor are discussed.

Laparoscopic resection of calcifying fibrous pseudotumor of the gastric wall. A unique case report.

Calcifying fibrous pseudotumor (CFPT) is a recently described peculiar lesion characterized by the presence of abundant hyalinized collagen with psammomatous or dystrophic calcifications and a lymphoplasmacytic infiltrate. Initially, a few cases of CFPT were observed in the subcutaneous and deep soft tissues, especially at the level of the extremities, trunk, scrotum, groin, neck, and axilla; more recently, several cases have been reported in the pleura. We present a case of CFPT of the gastric wall. To our knowledge, this is the first such case to be described. A previously healthy 49-year-old woman presented with a 5-month history of epigastric pain after eating, early satiety, and weight loss. Gastroscopy revealed a polypoid lesion covered by normal mucosa along the great curvature of the gastric body. The patient was submitted to surgical treatment consisting of laparoscopic wedge resection of the gastric body. Histologic examination of the specimen disclosed CFPT affecting the wall of the gastrointestinal tract. The postoperative course was uneventful, and the patient was discharged from the hospital 5 days after surgery. The patient was free of disease 6 months after excision. Herein we discuss the clinicopathological features and surgical treatment of this most unusual case.

Reactivity to recombinant house-dust-mite allergens in asthma and rhinitis in a tropical environment.

BACKGROUND: House-dust mites contain components that are allergenic in mite-sensitive patients, and a number of these have been produced in recombinant form. METHODS: In the present study, we evaluated by skin prick testing the positivity to native Der p 2 and recombinant Der p 2, Der p 5, and Der p 7 allergens of Dermatophagoides pteronyssinus in patients with rhinitis, asthma, or a combination of these diseases, who were positive to whole-mite extract. RESULTS: In all patients, the positivity to both native and recombinant Der p 2 was high. In patients with either rhinitis or asthma, the reactivity to Der p 5 and 7 was significantly lower than to Der p 2. However, in patients with combined disease, the positivity to the minor allergens was almost as high as that to Der p 2. CONCLUSIONS: These results raise the question of whether patients with combined allergic rhinitis and asthma, when compared to those with either of these diseases alone, are predisposed to react to a wider range of mite allergens, or, inversely, whether patients who respond to the minor allergens are more susceptible to suffering the combined disease.

Biological activity of recombinant Der p 2, Der p 5 and Der p 7 allergens of the house-dust mite Dermatophagoides pteronyssinus.

Der p 2, Der p 5 and Der p 7 are three allergens of the house-dust mite Dermatophagoides pteronyssinus that have been cloned and expressed in Escherichia coli as fusion proteins with glutathione-S-transferase (GST). We showed that these recombinant allergens produced immediate hypersensitivity skin-test reactions in 70, 60 and 52% respectively of a group of mite-sensitive allergic patients who were strongly positive to whole mite extract (WME). Comparable positivities were found for serum levels of specific IgE antibody against these allergens, as measured by the radioallergosorbant test (RAST). Overall, for the group of allergic patients that we evaluated, the serum IgE antibody concentrations against Der p 2, 5 and 7 were calculated to represent about one third, one quarter and one fifth respectively of the levels measured against the WME. However, for some patients the activity determined against the separate allergens was far higher than that detected against the WME, thus indicating that the concentration of these can be limiting in the WME. We found no significant correlations between the RAST levels against Derp 2 and either Derp 5 or 7, and RAST-inhibition tests indicated a lack of cross-reactivity between Der p 2 and the other two allergens. In contrast, the RAST results revealed the existence of a significant immunological relationship between Der p 5 and 7. Although a certain degree of reactivity against the GST fusion partner was found in the allergic patients studied, this was not a significant influence in determining the positivity against the recombinant allergens. These results confirm the in vivo biological activity of recombinant Der p 2, 5 and 7, and indicate that whilst Der p 2 is undoubtedly a major mite allergen, both Der p 5 and 7 make important contributions toward the overall allergenic activity of house-dust mites.

Verruga peruana: an infectious endemic angiomatosis.

Microbial-related dysplastic and neoplastic angiomatous proliferative processes are seen with increased frequency, particularly in the acquired immunodeficiency syndrome (AIDS). The microbial-encoded or -induced mediators of angiopathogenesis in AIDS-associated Kaposi's sarcoma and bacillary angiomatosis are actively being sought. The present review addresses the historical, epidemiologic, clinical, etio- and histopathogenic aspects of the verruga peruana (VP). VP is a disease thus far endemic to high Andean valleys and characterized by dermal angioblastic proliferation in association with reactivation of latent Bartonella bacilliformis organisms. VP closely resembles AIDS-associated angiopathogenic manifestations at the clinical, histopathologic, and etiologic levels and therefore has been proposed as a model for the study of angiogenesis and endothelial cell dysplasia and neoplasia. Moreover, the recent epidemic outbreaks in endemic areas, the increased frequency of international travel to the region, the variable incubation period, and the possibility of not recognizing VP due to its rarity further underscore the relevance of studying this rare disorder and of including it in the differential diagnosis of angiomatous-proliferative disorders.

Promoting effect of bombesin on the cell proliferation in the rat endocrine pancreas during the early postnatal period.

The present work investigated whether orally administered bombesin influences cell proliferation in the endocrine pancreatic islets of rats during the suckling period and after weaning. Four series of pups were given bombesin diluted in milk (20 micrograms/kg, 3 times daily) or milk alone for 5 days during either the first, second, third or fourth postnatal week of life. Oral administration was used because bombesin-like peptides have been identified in the breast milk of mammals. 45 min before death, animals were given a single [3H]thymidine pulse injection. Tissue sections were processed for radioautography; DNA labeling and mitotic indices were estimated after counting at least 1000 endocrine cells per rat pancreas. In control rats, the labeling and mitotic indices in pancreatic islets dropped regularly from the first week to the fourth week of life (3.6% +/- 0.2% versus 1.9% +/- 0.1% and 0.46% +/- 0.09% versus 0.08% +/- 0.02%, respectively). Orogastric bombesin administration significantly increased the DNA labeling and mitotic indices at the end of the first week (+20% and +62%, respectively) and second week of life (+37.5% and +49%, respectively) (P less than 0.05 to P less than 0.005), but did not modify these parameters for the third and subsequent weeks of life. Therefore, this study provides evidence that bombesin stimulates DNA synthesis and cell division in pancreatic endocrine cells during the developmental period.