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Biomedical subjects

M Stella

Publications and source records attributed to M Stella.

At least 55 records · Page 3Linked to original sources

Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial.

OBJECTIVE: Our purpose was to investigate the efficacy of postsurgical treatment with nafarelin in women with advanced endometriosis. STUDY DESIGN: Eligible for trial were women < or = 38 years old with unexplained infertility with or without chronic pelvic pain and stage III or IV endometriosis according to the American Fertility Society, revised, classification who underwent laparotomy as first surgical treatment for debulking or radical surgery of endometriotic lesions. Patients were assigned according to a randomization list to nasal nafarelin, 400 micrograms/day (36 subjects) or placebo nasal spray (39 subjects) for 3 months. Pelvic pain was assessed before first surgery and at the 12-month follow-up visit in women with pelvic pain by means of a multidimensional score system and a 10-point linear pain scale. RESULTS: No marked differences in pain scores emerged among women allocated to different treatments. The mean reduction of the multidimensional score was 3.6 and 4.0, respectively, in women allocated to nafarelin and placebo and of the 10-point linear scale scores was 7.0 and 6.9. These differences were not statistically significant. Within 1 year from randomization, of the 36 women allocated to nafarelin and the 39 allocated to placebo, seven (19%) and seven (18%), respectively, became pregnant. CONCLUSION: This study suggests that medical treatment with nafarelin does not markedly improve pelvic pain and short-term reproductive prognosis in women with stages III and IV endometriosis.

Administration, Intranasal↗

Sensory endings in skin grafts and scars after extensive burns.

Fifteen patients who underwent a split thickness skin graft operation for full thickness burns and six patients with postburn scars were biopsied after a standard aesthesiological examination completed with Weber and Dellon tests. A semiquantitative evaluation was performed on immunohistochemically stained sections to determine the presence or absence of PGP 9.5 immunoreactive intraepithelial fibres, complex sensory receptors, nerve fibres in the dermal papillae, vessel-innervating fibres, gland-innervating fibres, and nerve trunks in the deep dermis. The reinnervation pattern was similar in grafts and scars. With regard to sensory receptors, free nerve endings and Merkel-neurite complexes were observed. Statistical analysis suggested a significant correlation between sensibility and the amount of regenerated nerve structures (particularly in the epidermis and dermal papillae).

Analysis of Variance↗

Similar ectopic expression of ICAM-1 and HLA class II molecules in hypertrophic scars following thermal injury.

In previous studies we have shown that HLA Class II antigens are expressed by keratinocytes and fibroblasts in hypertrophic scars. Because of the potential role of immunological events in the pathogenesis of hypertrophic scars, in the present study we have tested hypertrophic scars for the expression of intercellular adhesion molecule-1 (ICAM-1), a molecule which plays an important role in immunological phenomena. Immunoperoxidase staining with anti-ICAM-1 MoAb of 10 hypertrophic scar samples detected this molecule on epidermal keratinocytes and on about 30 per cent of fibroblasts at the site of lymphoid infiltration. The expression of ICAM-1 in hypertrophic scars was similar to that of HLA Class II antigens. Since the concomitant expression of ICAM-1 and HLA Class II by keratinocytes is known to enhance their antigen-presenting properties, the present results support the possibility that immunological events play a role in the disruption of the normal processes of wound healing and tissue remodelling which result in hypertrophic scars.

Adult↗

Altered biosynthesis of tumour necrosis factor (TNF) alpha is involved in postburn hypertrophic scars.

The present study shows that the decrease of TNF alpha in postburn hypertrophic scars is due to a decrease in the steady-state level of TNF alpha mRNA and thus to an altered biosynthesis of the cytokine. Thirteen scars, including seven hypertrophic and six normotrophic scars, were tested for TNF alpha mRNA production by a semiquantitative reverse polymerase chain reaction (PCR) method. TNF beta and beta actin were tested as a control. Six out of six normotrophic scar samples amplified with primers for TNF alpha showed a positive PCR signal up to the 1:32 dilution. On the contrary all the hypertrophic tested samples (7/7) had a positive PCR signal only at the 1:1 or 1:2 dilution. All samples, both normotrophic and hypertrophic, were homogeneous as to TNF beta production.

Actins↗

Radioimmunoguided surgery using iodine-125-labeled biotinylated monoclonal antibodies and cold avidin.

UNLABELLED: One of the limitations of intraoperative tumor detection with radiolabeled monoclonal antibody (Mab), by means of a gamma-detecting probe (GDP), is the long time interval needed between Mab injection and surgery to obtain low blood-pool activity. Such an interval can be shortened considerably, exploiting the high affinity between avidin and biotin. METHODS: Twenty patients with colorectal cancer were injected with 1 mg of biotinylated 125I monoclonal antibodies followed, 48 hr later, by a chase of cold avidin. During surgery, the GDP was used to detect radioactive emissions from the tumor and normal tissue. Tumor tissue samples were analyzed in vitro by immunohistochemical tests for the presence of tumor antigens and in vivo antibody localization. RESULTS: At the time of surgery (average 7 days postinjection), the mean value of circulating radioactivity was 6% +/- 3% of the injected dose. Of 20 patients studied, tumors were localized in 13 cases (65%). Subclinical tumors were detected in 3 patients (15%). CONCLUSION: The use of 125I-labeled biotinylated Mabs followed by avidin as a chase enhances the applicability and effectiveness of radioimmunoguided surgery technology and will allow the use of radioisotopes with a shorter half-life than 125I.

Antibodies, Monoclonal↗

Role of B72.3 iodine 125-labeled monoclonal antibody in colorectal cancer detection by radioimmunoguided surgery.

BACKGROUND: Radioimmunoguided surgery (RIGS) by means of radiolabeled monoclonal antibodies and a probe has been reported to be useful in recognizing subclinical tumor deposits during operation. Aim of this study was to understand the limits of this technique and to assess the potential diagnostic use of RIGS in colorectal cancer surgery. METHODS: Monoclonal antibody B72.3 reacting with TAG 72 antigen, labeled with iodine 125, was injected in 32 patients with primary tumors and in 22 patients with recurrent colorectal cancer. One hundred thirty-three suspected tumor sites were evaluated during operation by means of probe and resected with immunohistochemistry as control. RESULTS: Primary tumor sites were localized by RIGS in 60% of cases, and recurrent sites were localized in 82% of cases. There was a significant correlation both for primary (p < 0.001) and recurrent (p < 0.001) tumor sites between intraoperative RIGS findings and TAG 72 tumor antigen expression. Results obtained with the probe were instrumental in modifying the surgical approach in six (27%) of 22 patients with recurrences, allowing the removal of tumor masses that would otherwise have been overlooked. CONCLUSIONS: The results of RIGS seems to be encouraging in terms of clinical use. The potential high diagnostic resolution appears to improve surgical ablation of colorectal cancer, especially in patients with recurrent cancer or suspected recurrent tumors who have negative results for intraabdominal disease by all other roentgenographic criteria with rising carcinoembryonic antigen or TAG 72 antigen levels.

Adult↗

Prospective assessment of functional results after ileal J pouch-anal restorative proctocolectomy.

OBJECTIVE: To document the functional results of 50 consecutive patients who underwent hand-sewn ileal J pouch-anal restorative proctocolectomy for ulcerative colitis between 1988 and 1991 (mean follow-up, 18.1 months; range, 6 to 48 months). DESIGN: Patients recorded their observations daily over 1 week. The patients completed these weekly diaries every 3 months for the first year and then at 18, 24, 36, and 48 months after ileostomy closure. STUDY PARTICIPANTS: Fifty patients (mean age, 31 years; 24 males). SETTING: The University of Chicago (Ill). RESULTS: Stool frequency at 3, 6, 12, and 24 months was 6.3 +/- 2.1, 5.5 +/- 2.4, and 5.1 +/- 1.9, and 5.9 +/- 1.6 per day, respectively, without urgency. Fifty-four percent were perfectly continent; 18% had occasional spotting (one or two leaks per week); 12% had minor leakage (three to seven per week); and 16% had major leakage (more than seven per week). In these three groups, loss of solid feces never occurred in 84%, 88%, and 65% of patients, respectively. Females had more severe incontinence than males, but continence improved over time for both sexes. Twenty-two percent of female patients developed dyspareunia; no males developed impotence, but 19% had retrograde ejaculation. The probability of experiencing pouchitis increased with time from 15% at 6 months to 40% at 12 months, and 50% after 24 months. CONCLUSIONS: These results represent an accurate assessment of patient function after ileal J pouch-anal anastomosis. We encourage the use of a prospective, patient-completed protocol to obtain a realistic assessment of functional results.

Adolescent↗

TNF production and hypertrophic scarring.

The percentage of TNF alpha- and beta-positive cells was analyzed in hypertrophic scar (N = 13), normotrophic scar (N = 7), and normal skin (N = 6) biopsies using monoclonal antibodies and immunoperoxidase staining of cryostat tissue sections. Samples were first characterized for infiltrating cells. In hypertrophic samples there was a significant increase in activated infiltrating cells, capable of producing TNF beta and IL-1 beta. In contrast, the percentage of TNF alpha-positive cells was significantly lower than that detected in normotrophic scars. In fact, in hypertrophic scar samples a positive staining with anti-TNF alpha mAb was restricted to 8% of tissue-infiltrating cells compared to 35.4% of the cells present in normotrophic scars; 12% of infiltrating cells were stained in normal skin sections. These results suggest that TNF alpha may be important for normal wound healing and that hypertrophic scarring might be partially a consequence of a low amount of TNF alpha.

Adolescent↗

The importance of blood cell-vessel wall interactions in tumour metastasis.

Tumour cell dissemination is a complex process, depending on the ability of malignant cells to escape from the primary tumour and penetrate and flow through the bloodstream. Circulating tumour cells can adhere to the vessel wall, dissolve the basal lamina and extravasate, giving origin to metastases. Interactions between tumour cells, blood platelets and leukocytes favour tumour cell adhesion to the vessel wall, migration in extravascular spaces and growth in secondary sites. The biochemical and molecular mechanisms regulating tumour cell adhesion to the vessel wall and intercellular contacts have been studied extensively in recent years. Moreover, it has been shown that either tumour cells or blood cells release growth factors and inflammatory proteins, such as cytokines and chemokines, that may be involved in tumour cell migration and proliferation. Finally, tumour cells and cells of the surrounding tissue possess procoagulant and fibrinolytic properties that may be important in modulating the extracellular matrix around the tumour, to allow tumour cell invasion and progression. We have described the cell types (i.e. blood platelets, leukocytes, endothelial cells), the matrix components (i.e. fibronectin, thrombospondin and laminin) and the growth factors/cytokines (i.e. platelet-derived growth factor, transforming growth factor beta, tumour necrosis factor) involved in these processes. In particular, we have described cell-cell and cell-matrix interactions, cell migration and release of growth factors, cytokines, chemotactic peptides and proteolytic enzymes. This survey has also considered a few innovative approaches for the prevention and cure of cancer and metastasis that are based on these new concepts.

Amino Acid Sequence↗

Incidence, diagnosis, and treatment of enteric and colorectal fistulae in patients with Crohn's disease.

OBJECTIVE: The authors review their experience, evaluating the incidence and examining the various modalities employed in the diagnosis and treatment of patients with Crohn's disease complicated by fistulae. SUMMARY BACKGROUND DATA: Although common, internal and external fistulae in Crohn's disease may pose challenging problems to the surgeon. METHODS: Of 639 patients who underwent surgical treatment at the University of Chicago between 1970 and 1988 for complications of Crohn's disease, 222 patients (34.7%) were found to have 290 intra-abdominal fistulae. RESULTS: A fistula was diagnosed preoperatively in 154 patients (69.4%), intraoperatively in 60 (27%), and only after examination of the specimen in 8 (3.6%). The fistula represented the primary or single indication for surgical treatment in 14 patients (6.3%) and one of several indications in the remaining patients. Of 165 patients with an abdominal mass or abscess, 69 (41.8%) had a fistula. All patients underwent resection of the diseased intestinal segment; 160 (73.1%) with primary anastomosis and the remaining 62 with a temporary or permanent stoma. The fistula was directly responsible for a stoma in only 16 patients (7.2%) and was never responsible for a permanent stoma. Resection of the diseased bowel achieved en bloc removal of the fistula in 145 cases. Removal of 93 additional fistulae required resection of the diseased bowel segment along with closure of a fistulous opening on the stomach or duodenum (n = 14), bladder (n = 35), or rectosigmoid (n = 44). When the fistula drained through a vaginal cuff (n = 4), the opening was left to close by secondary intention; when the fistula opened through the abdominal wall (n = 46), the fistulous tract was debrided. In the remaining two entero-salpingeal fistulae, en bloc resection of the involved salpinx accomplished complete removal of the fistula. There was a dehiscence of one duodenal and one bladder repair; 14 patients (6%) experienced postoperative septic complications and one patient died. CONCLUSIONS: Fistulae are diagnosed preoperatively in 69% of cases and can be suspected in as many as 42% of patients with an abdominal mass. Fistulae are the primary or single indication for surgical treatment and are directly responsible for a stoma only in a few patients. Treatment, based on resection of the diseased bowel and extirpation of the fistula, can be accomplished with minimal morbidity and mortality.

Adult↗

Localization of biotinylated monoclonal antibodies (B72.3 and F023C5) in patients with colorectal cancer.

The recognition and treatment of neoplastic lesions in early phases are among the most important aims of research using monoclonal antibodies (MoAb). Recent studies have demonstrated that the use of radiolabelled MoAb directed against tumor associated antigens and hand-held gamma detecting probe (GDP) could help in the recognition of primary tumors and metastases. The goal of this study was to investigate the in vivo antibody reaction as shown by histologic preparations after injection of 125I biotinylated MoAb (B72.3 or F023C5) before surgery and to compare the immunohistochemical results with those obtained with GDP in colorectal cancer. We studied 15 cases of patients with primary or recurrent colorectal cancer. The biotinylated, radiolabelled antibody administered in vivo could be seen in frozen sections with streptoavidin peroxidase complex. In 14 cases there was agreement between GDP observations and detection of the in vivo injected biotinylated MoAb with direct staining using streptoavidin peroxidase conjugate. The use of MoAbs thus provides a means of correlating the intraoperative signal with the presence of the injected antibodies on the tumor.

Antibodies, Monoclonal↗

Membrane association and shedding of the GPI-anchored Ca-MOv18 antigen in human ovary carcinoma cells.

The antigen recognized by the MOv18 MAb (Ca-MOv18) was recently shown to be a glycosylphosphatidylinositol (GPI)-linked protein. In this report we show that GPI-anchorage is not limited to IGROVI cells nor to other ovary carcinoma cell lines, but Ca-MOv18 was also found to be sensitive to phosphatidylinositol-specific phospholipase C (PI-PLC) treatment on fresh ovarian cancer cells. Furthermore, we found a heterogeneous sensitivity of Ca-MOv18 to PI-PLC cleavage, not only among the different cells studied but also in different experiments performed on the same cell line, during extended periods of time in culture. Sensitivity to PI-PLC cleavage was determined by immunofluorescence on live cells and by double-determinant radioimmunoassay of the antigen released in the supernatant. The specificity of the PI-PLC cleavage was demonstrated as follows: (a) TX114 solubilized Ca-MOv18 shifts from the detergent to the aqueous phase after treatment with PI-PLC; (b) on membrane preparations, PI-PLC specifically released a fraction of the antigen, which is distinct from the weakly associated form released by high-salt treatment; (c) Ca-MOv18 from IGROVI expressed the cross-reacting determinant (CRD), which is characteristic of GPI-linked molecules. The absence of CRD expression on the spontaneously released protein and the possibility of artificially inducing antigen shedding during the resynthesis of Ca-MOv18 which follows bacterial PI-PLC treatment are interesting points which need to be further investigated in order to understand the physiology of the Ca-MOv18 tumor antigen.

Antibodies, Monoclonal↗

Value of cytogenetics in the differential diagnosis of the small round cell tumors of childhood.

Small round cell tumors are among the most common problems in the differential diagnosis of cancer, even when more sophisticated histological techniques are utilized (Ezinger and Weiss: In Soft Tissue Tumors. St. Louis: CV Mosby, 1988, pp 668-683). Six cases of small round cell tumors are described the diagnosis of which was particularly difficult. Cytogenetic analysis provided useful information in all of them in making the definitive diagnosis. The reported cases stress the value of cytogenetic methods in approaching difficult diagnostic problems.

Adolescent↗

Biochemical characterization of Trop-2, a cell surface molecule expressed by human carcinomas: formal proof that the monoclonal antibodies T16 and MOv-16 recognize Trop-2.

Trop-2 is a cell surface structure recognized by the 162-46.2 mAb and expressed by most human carcinomas. Since the 162-46.2 mAb works poorly in immunoprecipitation, to characterize the structure of Trop-2 we searched for other mAbs directed against this molecule. Selection of candidates was performed by analyzing the characteristics of mAbs directed against epithelial cells and by comparing the staining pattern of each mAb with the one of the 162-46.2 on frozen sections of human epidermis. Two mAbs, T16 and MOv-16, were selected for further analysis. Formal proof that candidate mAbs reacted with Trop-2 was obtained by comparing their binding patterns to mouse L cells transfected with the Trop-2 gene by genomic DNA transfection and selected by FACS using the FITC-162-46.2 mAb. In immunofluorescence FACS analysis the FITC-T16 and FITC-MOv-16 mAbs specifically stained Trop-2 transfectants. The specificity of binding was confirmed by selective blocking of the staining by the respective unconjugated mAb. Interestingly, cross-blocking studies indicated that the 162-46.2, T16 and MOv-16 mAbs recognize the same epitope or closely spaced ones on the Trop-2 molecule. T16 and MOv-16 efficiently immunoprecipitate Trop-2 from Trop-2 transfectants and from the human cell line OVCA-432, indicating that it is a cell surface glycoprotein, with an apparent molecular weight of 57 kD in non-reducing conditions. A weaker band of 38 kD is often co-precipitated with the 57 kD form in an apparently specific manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Morphology of corpuscular receptors in hairy and nonhairy human skin as visualized by an antiserum to protein gene product 9.5 compared to anti-neuron-specific enolase and anti-S-100 protein.

The present study elucidates the morphology of encapsulated receptors in human skin by means of immunohistochemistry for the recently characterized neurospecific marker protein gene product 9.5, in comparison with neuronal specific enolase and S-100 protein. Only two types of corpuscles are identified, Meissner's corpuscles and simple coiled corpuscles. Moreover, this investigation reveals that though regional specialization may exist with regard to the encapsulated receptor density, the comparison of hairy and nonhairy skin does not reveal important differences.

Biomarkers↗

Comparative study of Langerhans cells in normal and pathological human scars. I. Atrophic scars.

In the present study, we investigated Langerhans cells (LCs) in the epidermal component of human atrophic scars, comparing them with those in control skin and normotrophic scars. A preliminary analysis of the histological features was first carried out on vertical serial sections, stained with hematoxylin and eosin. The total epidermal thickness and the thickness of the single epidermal layers were then measured, by means of a digitizing tablet and a morphometric program run on an Apple IIe computer. These parameters were found to be significantly lower (40%) in atrophic scars, if compared to control skin and normotrophic scars (p less than 0.05). CDla-positive and HLA-DR-positive LCs were marked by indirect immunofluorescence. Their position among the epidermal layers, their dimensions, their density and their morphology were examined. In atrophic scars, LCs were densely and evenly distributed in all the epidermal layers. Their density was increased (about 1200 cells/mm2 of epidermal area), if compared to control skin and normotrophic scars (both 300-400 cells/mm2 of epidermal area; p less than 0.001). The CDla-positive definite cell bodies, exhibiting an unstained nucleus, were as large as those evidentiated in the normotrophic scars and twice as much the control skin values (p less than 0.001). The present results provide morphological data that distinguish atrophic scars from control skin and normotrophic scars, and suggest an involvement of the Langerhans cells in this particular case of pathological scarring.

Adolescent↗