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Biomedical subjects

A Fichera

Publications and source records attributed to A Fichera.

At least 19 recordsLinked to original sources

Familial rectal carcinoid: report of two first-degree relatives with rectal carcinoid and review of the literature.

Two brothers with familial carcinoid tumors of the rectum are presented. A few cases documenting the occurrence of carcinoid tumors in first-degree relatives in the absence of the multiple endocrine neoplasia (MEN) syndromes have been reported in the literature. Consistent with these previous reports, in this case both patients had gastrointestinal carcinoid tumors that are located in identical anatomic locations. The current literature on carcinoid tumors outside the setting of any known genetic syndrome is reviewed. Clinical relevance and screening recommendations are discussed.

Adult↗

High perinatal survival in monoamniotic twins managed by prophylactic sulindac, intensive ultrasound surveillance, and Cesarean delivery at 32 weeks' gestation.

OBJECTIVES: Increased perinatal mortality in monoamniotic twin pregnancies is attributed to cord accidents in utero and at delivery. We evaluated the following parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement; (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie; and (3) the perinatal outcome with our current management paradigm. METHODS: This is a retrospective review of monoamniotic pregnancies of >or=20 weeks' gestation managed with serial ultrasound surveillance, medical amnioreduction and elective Cesarean delivery at 32 weeks' gestation. Mean amniotic fluid index (AFI) and change in AFI in monoamniotic pregnancies managed with oral sulindac was compared with 40 gestation-matched monochorionic-diamniotic controls. RESULTS: Among 44 monoamniotic pregnancies, 20 with two live structurally normal twins at 20 weeks' gestation satisfied the inclusion criteria. All fetuses survived to 28 days postnatally despite early prenatal cord entanglement in all but one case. Whereas AFI remained stable throughout gestation in the controls, the AFI fell in those patients on sulindac from a mean value of 21.0 cm (95% CI, 18.5-23.6 cm) at 20 weeks to a mean of 12.4 cm (95% CI, 10.1-14.6 cm) at 32 weeks (ANOVA P across gestation = 0.001) but mainly remained within normal limits. Fetal lie was stabilized in 11/20 cases in the monoamniotic group compared with 13/40 in the control group (P < 0.0001). CONCLUSIONS: Cord entanglement appears unpreventable, as it typically occurs in early pregnancy. Sulindac therapy reduces AFI, leads to more stable fetal lie, and may prevent intrauterine death by diminishing the risk of constricting cords that are already entangled. Perinatal survival in monoamniotic pregnancies managed by a regime of sulindac from 20 weeks' gestation, close ultrasound surveillance and elective abdominal delivery at 32 weeks' gestation seems empirically higher than that in the literature.

Amniocentesis↗

Metaanalysis of trials comparing laparoscopic and open surgery for Crohn's disease.

BACKGROUND: Several studies in the literature have suggested that laparoscopic surgery for Crohn's disease is associated with faster postoperative recovery and a morbidity and recurrence rate similar to that for open surgery. Most of these studies have been limited by a small sample size and a short follow-up period. METHODS: To clarify whether open or laparoscopic resection results in a better outcome, a metaanalysis of studies was performed comparing the two procedures for Crohn's disease. Pooled effects were estimated using a random-effects model. RESULTS: Laparoscopic surgery required more operative time than open surgery (26.8 min; 95% confidence interval [CI], 6.4-47.2 min), but resulted in a shorter duration of ileus and a decreased hospital stay (-2.62 days; 95% CI, -3.62 to -1.62). Laparoscopic surgery also was associated with a decreased rate for postoperative bowel obstruction and surgical recurrences. CONCLUSIONS: Laparoscopic surgery for Crohn's disease is feasible, safe, and associated with shorter duration of ileus and a shorter hospital stay.

Clinical Trials as Topic↗

Increased latency of absent end-diastolic flow in the umbilical artery of monochorionic twin fetuses.

OBJECTIVE: To determine if absent end-diastolic flow (AEDF) in the umbilical artery (UA) has a longer latency in monochorionic (MC) twin fetuses compared to singleton or dichorionic twin (DC) fetuses. METHODS: One hundred and eight pregnancies with a fetus with AEDF were reviewed: 47 MC and 17 DC twin pregnancies and 44 singletons. Because twin-twin transfusion syndrome (TTTS) is a potential confounder when determining latency, subgroup analysis was also performed on the 21 MC affected pregnancies without TTTS. Latency of AEDF (in days) was defined as the difference between the gestational age at diagnosis of AEDF and gestational age at delivery or intrauterine death. RESULTS: Latency was similar in MC twins (median, 39 days) and DC twins (30 days) but longer compared to singletons (11 days; P = 0.0001). After excluding pregnancies with TTTS, latency in non-TTTS MC twins (54 days) was longer than in both singletons and DC twins. This was due to an earlier gestational age at AEDF in non-TTTS MC twins of 20 weeks compared to 27 weeks in both singleton and DC twins because median gestational age at delivery was similar in MC twins, DC twins and singletons. CONCLUSIONS: The latency period of UA AEDF is longer in MC twins than in singletons. Our data suggest that in MC twin fetuses without TTTS, AEDF begins earlier and lasts about twice as long as in DC twin fetuses, which is consistent with placental insufficiency not being the sole factor mediating abnormal UA waveforms in MC placentation. This observation is important in counseling and managing twin pregnancies discordant for AEDF.

Chorion↗

A coiled coil with a fluorous core.

The design, synthesis, and structural characterization of a highly fluorinated peptide system based on the coiled coil region of the yeast transcription factor GCN4 is described. All four leucine residues (a position) and three valine residues (d position) were replaced by the unnatural amino acids 5,5,5-trifluoroleucine and 4,4,4-trifluorovaline, respectively. The peptide is highly alpha-helical at low micromolar concentrations as judged by circular dichroism spectra, sediments as a dimeric species in the 5-30 microM concentration range, and exhibits a dimer melting temperature that is 15 degrees C higher than a control peptide with a hydrocarbon core. Furthermore, the apparent free energy of unfolding as calculated from guanidinium hydrochloride denaturation experiments is larger by approximately 1.0 kcal/mol for the fluorinated peptide than its hydrocarbon counterpart. We conclude that additional stability is derived from sequestering the more hydrophobic trifluoromethyl groups from aqueous solvent. These studies introduce a new paradigm in the design of molecular self-assembling systems, one based on orthogonal solubility properties of liquid phases.

Algorithms↗

A novel synthesis of enantiomerically pure 5,5,5,5',5',5'-hexafluoroleucine.

[reaction in text] A novel, short, and efficient synthesis of (S)-5,5,5,5',5',5'-hexafluoroleucine (6) in greater than 99% ee starting from the protected oxazolidine aldehyde 1 is described. The enantiomeric excess of the product was calculated from an NMR analysis of a dipeptide formed by reaction with a protected L-serine derivative. Furthermore, a racemic sample of N-acylated hexafluoroleucine was enzymatically resolved by treatment with porcine kidney acylase I and was found to have the same optical rotation as a synthetic sample of 6.

Amidohydrolases↗

Total mesenteric excision in the surgical treatment of rectal cancer: a prospective study.

BACKGROUND: Total mesorectal excision has been advocated in conjunction with low anterior or abdominoperineal resection as the optimal surgical treatment for rectal cancer. It involves removal of the entire rectal mesentery as an intact unit and maximizes the likelihood of obtaining a negative circumferential margin. OBJECTIVES: To prospectively validate the efficacy of total mesorectal excision in obtaining locoregional control, to identify the perioperative factors influencing the selection of either a sphincter sparing or a sphincter ablating procedure, and to identify independent factors that may influence long-term prognosis in rectal cancers. SETTINGS: Tertiary referral center. PATIENTS: Seventy-three consecutive patients with rectal cancer located within 10 cm of the anal verge were treated from 1984 to 1997 by the senior author (F.M.). Sixty-five patients form the basis of our analysis after the exclusion of 7 patients who had their cancer removed transanally and 1 patient who had a permanent diverting stoma as the only procedure. RESULTS: Twenty-six patients underwent a sphincter ablating procedure; 39 underwent a sphincter sparing procedure. Operative mortality was 1.5%. Follow-up was complete in 64 patients (39+/-30 months; range, 3-126 months). Five-year actuarial survival rates were 88% for the 34 patients with stage I and II adenocarcinoma and 65% for the 22 patients with stage III adenocarcinoma. The local recurrence rate was 6.2% overall, but only 3.1% in the potentially curable group (stages I-III). When only patients who did not receive adjuvant chemoradiation therapy were considered (n=23), local recurrence rate was 8.3% overall and 0% in the potentially curable group. Tumor stage (P=.04) and vascular and/or lymphatic invasion (P=.002) were statistically significant in their association with survival. Circumferential lesions (P<.001), gross invasion of contiguous organs (P<.001) and distance from the anal verge of less than 5 cm (P=.01) were statistically significant in their association with the choice of a sphincter ablating procedure. CONCLUSIONS: This study confirms the efficacy of total mesorectal excision in minimizing locoregional recurrence rates and confirms the well-established prognostic value of stage and microinvasion. Moreover, it indicates that circumferential lesions, distance from anal verge, and gross invasion of contiguous organs are significant perioperative factors in the selection of the type of surgical procedure.

Adult↗

Selective expression of carcinoembryonic antigen promoter in cancer cell lines: targeting strategy for gene therapy in colorectal cancer.

PURPOSE: This study was designed to characterize the mechanisms regulating the expression of the human carcinoembryonic antigen promoter (pCEA), in terms of tissue-specific targeting for gene therapy. The promoter was subcloned to a luciferase reporter gene (pCEA/Luc) in our laboratory and compared with a virally controlled luciferase vector (pSV40/Luc). METHODS: Four human cancer cell lines (HeLa, SW480, Caco2, and SW1116) were transfected with either pCEA/Luc or pSV40/Luc. Cells were treated with interferon-gamma and assayed at 72 hours after treatment. Carcinoembryonic antigen level was measured by enzyme immunoassay. Luciferase expression was measured at 48 hours and one week after transfection by luminometry. RESULTS: Luciferase activity after transfection with pCEA/Luc was higher in CEA-positive cells than in CEA-negative cells (P < 0.0001). pCEA/Luc demonstrated higher activity than pSV40/Luc in CEA-positive cells (P < 0.0001), but not in CEA-negative cells. In Caco2 cells, which before confluence are CEA-negative, luciferase expression increased on reaching confluence (P < 0.0001). Well to moderately differentiated cells responded to the interferon-gamma treatment, but the increase in CEA secretion did not correspond to an increase in pCEA/Luc expression. CONCLUSIONS: The expression of pCEA correlates well with the CEA production by the specific cell line offering a potential tissue-specific targeting strategy for colon cancer gene therapy. Furthermore, the tissue-specific CEA promoter has a higher and more persistent activity in CEA-positive human cancer cells than a viral promoter. The lack of response to interferon-gamma treatment suggests a different mechanism of action for interferon-gamma other than directly interacting with the promoter.

Carcinoembryonic Antigen↗

[Differential diagnostic problems in metastatic ovarian tumors of intestinal origin. Description of a clinical case].

The authors report the case of a patient undergoing gynecological surgery to the presence of a right ovarian mass with a maximum of diameter of 23 cm which was found to be a secondary tumour. Histologically analysis showed that this mass was the metastasis of a tumour of intestinal origin, a finding that was then confirmed by flow cytometry. The authors draw attention to the need for patients with suspected ovarian tumour to undergo preoperative diagnostic tests to evaluate the possibility of neoplastic pathology in the gastrointestinal tract in order to optimise surgery and antiblastic treatment.

Adenocarcinoma↗

Quantitation of in vivo gene delivery by restriction enzyme PCR generated polymorphism.

The Multiple intestinal neoplasia (Min) mouse develops multiple polyps in the intestine, due to a heterozygous mutation of the Apc locus. Our laboratory has been introducing normal human adenomatous polyposis coli (APC) gene into the Min mouse through liposome enema to prevent or reverse polyp formation. We have quantitated the amount of normal human APC gene delivered in vivo by a restriction enzyme site specific quantitative PCR. Adult Min and BALB/C mice were treated with lipofectant and human APC complementary DNA (cDNA) plasmid. Min colonic DNA was amplified using primers for Apc nucleotide 2524F (5'2524-TCTCGTTCTGAGAAAGACAGAAGCT) and 2679R (5"2679-TGATACTTCTTCCAAAGCTTTGGCTAT). Highlighted primer sequences were purposely different so as to generate two HindIII restriction enzyme sites in the presence of normal mouse Apc (Apc+). Genomic DNA from untreated Min colonic epithelium revealed two bands: 144 bp for ApcMin and 123 bp for Apc+. BALB/C DNA was amplified using primers flanking a region within the APC gene containing a HindIII site on the human APC, which is absent in the murine APC (Apc). Min's DNA extracted 24 hr after treatment demonstrated a plasmid content of 3% due to a relative increase in the Apc+ (123 bp) band. Six weeks of treatments increased delivery to 10%. APC gene therapy of colonic epithelium can be quantitatively measured through restriction enzyme quantitative PCR. Long-term treatment further increases gene delivery. PCR generated polymorphism is a reliable and reproducible technique to initially optimize transfection conditions and ultimately quantitate efficacy in an in vivo gene delivery model.

Adenomatous Polyposis Coli↗

Incidence and therapeutic implications of synchronous colonic pathology in colorectal adenocarcinoma.

BACKGROUND: The presence of synchronous benign and malignant colonic pathology may influence the magnitude of surgery for colorectal adenocarcinoma. The aim of this prospective study was to quantitate the need for a more extensive surgical procedure because of synchronous pathology in colorectal cancer patients. METHODS: Between 1984 and 1996, 235 consecutive patients were treated for colorectal adenocarcinoma. Preoperative survey of the colon in 228 patients included colonoscopy (91%) and double contrast barium enema (35.7%). Seven patients were excluded for incomplete preoperative survey because of perforating or obstructing colon carcinoma or acute ulcerative colitis. RESULTS: One hundred four patients (45.6%) had the following synchronous colonic lesions: benign polyps (68 patients, 29.8%), diverticular disease (30, 13.1%), ulcerative colitis (10, 4.4%), synchronous adenocarcinoma (8, 3.5%), and Crohn's colitis (3, 1.3%). Pathologic examination demonstrated three additional synchronous adenocarcinomas for a total of 11 patients (4.9%). Twenty-five (11%) required more extensive surgery than dictated by the primary cancer. Of these 25 patients, 17 had a benign or premalignant condition associated with their carcinoma and 8 had a synchronous carcinoma. Seventeen patients underwent a sphincter-saving procedure. Of the remaining eight patients requiring sphincter ablation, seven were needed because of a synchronous nonmalignant lesion, rather than because of the primary tumor. CONCLUSIONS: In our patient population, the incidence of synchronous colorectal lesions was 45.6%. Synchronous colorectal cancer occurred in 4.9%. In 11%, the presence of synchronous colorectal lesions made the surgical procedure more extensive than that dictated by the primary cancer, and in 3%, the need for a sphincter ablating procedure was dictated by a synchronous nonmalignant lesion.

Adenocarcinoma↗

Introduction of human adenomatous polyposis coli gene into Min mice via cationic liposomes.

BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor-suppressor gene involved in familial polyposis coli (FAP), a hereditary disease heralded by the development of hundreds of colorectal adenomas. A mouse model for FAP, the multiple intestinal neoplasia (Min) mouse, develops multiple adenomatous polyps of the large and small intestine similar to their human counterparts. To test the feasibility of introducing normal human APC as a means of either preventing or reversing polyp formation, we describe a method of in vivo transfection of APC into colonic epithelium of the Min mouse. METHODS: Anesthetized young (4 weeks) Min mice were treated with enemas containing lipofectant and a normal human APC cDNA plasmid every 72 hours for 2 months and then euthanized at 24, 48, and 72 hours after the last treatment. Polymerase chain reaction (PCR) was used to detect the presence of the plasmid DNA. RESULTS: PCR on the extracted colonic epithelial DNA showed the presence of plasmid DNA up to 72 hours after the last treatment. Expression of the plasmid construct was confirmed by reverse transcriptase-PCR. CONCLUSIONS: We have demonstrated the repeated introduction and detection of normal human APC in the colonic epithelium of the Min Mouse in vivo during an extended period of time with no toxic side effects by means of our prolonged therapy.

Adenoma↗

[A modified Hill's procedure in the surgical treatment of hiatal hernia].

After an introduction on the problems regarding indications and surgical management of gastro-oesophageal reflux disease, the Authors describe the technique they use, which is a modification of Hill's posterior gastropexy, involving the placement of suture through the median arcuate ligament, without exposing the celiac axis. The preliminary results of a prospective randomized clinical trial, conducted at the Surgical Clinic Department of Catholic University, Rome, are described. The trial evaluated early and late results of Hill's modified technique versus a control group, in which a Dor technique has been used. Intraoperative oesophageal manometry has been performed in both groups, to set the cardioplasty more properly. Ninety-one patients out of 132 have been studied; 65 had a good response to medical therapy and 26 have been operated upon. In 9 cases (6 Dor and 3 Hill) intraoperative manometry was performed. All patients have been studied pre-operatively with upper g.i. series, endoscopy with biopsies, oesophageal manometry and 24-h pH monitoring; this protocol has been repeated after 3 to 6 months postoperatively, to evaluate the results more accurately. The preliminary data, although statistically non significant because of the small study group, seem to favour the Hill modified technique, both for complication and reflux control. Further data are needed to confirm them.

Adult↗