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Biomedical subjects

M Stella

Publications and source records attributed to M Stella.

At least 19 recordsLinked to original sources

Laparoscopic billroth II gastrectomy for completely stricturing duodenal ulcer: technical details.

BACKGROUND: The authors report a series of three patients who underwent laparoscopic gastrectomy for gastric outlet obstruction due to stricturing duodenal ulcer. MATERIALS AND METHODS: In all cases an intracorporeal resection of the antrum and an antecolic end to side gastrojejunostomy (Billroth II) were performed. Technical details are discussed in the paper. RESULTS: Mean operative time was 260 minutes, mean blood loss was 43 millilitres. There were no postoperative complications and all patients were discharged on the fifth postoperative day. A follow up of three years shows that no patient had recurrence and post-gastrectomy syndromes. CONCLUSIONS: Laparoscopic Billroth II gastrectomy is a safe and feasible procedure with benefits such as quick hospital stay, decreased postoperative pain, good cosmesis and reduced morbidity.

Adult↗

Activity of GH/IGF-1 axis in burn patients: comparison with normal subjects and patients with GH deficiency.

The aim of this study was to clarify the activity of GH/IGF-1 axis as well as the variations of nutritional parameters following a thermal injury in man. To this goal, in 22 patients with burn [BURN, age (mean+/-SE): 46.5+/-3.4 yr, BMI: 25.0+/-0.8 kg/m2, % burn surface area: 26.0+/-3.0%, ROI score: 0.22+/-0.1] we evaluated IGF-1, IGF binding protein (IGFBP-3), GH, GH binding protein (GHBP), pre-albumin (pre-A), albumin (A) and transferrin (TRA) levels on days 1, 3, 7, 14 and 28 after intensive care unit (ICU) admission. IGF-1, IGFBP-3, GH and GHBP levels were also assayed basally in 29 normal subjects (Ns) (Ns, age: 47.5+/-2.8 yr, BMI: 22.0+/-1.4 kg/m2) and in 34 panhypopituitary patients with severe GH deficiency (GHD, age: 42.7+/-2.5 yr, BMI: 25.6+/-0.8 kg/m2). On ICU day 1, IGF-1 and IGFBP-3 in BURN were higher than those in GHD (p<0.05 for both, respectively) and lower than those in Ns (p<0.05) while GH levels in BURN did not differ from those in Ns and higher than GHD (p<0.01). In BURN, IGF-I and IGFBP-3 levels showed a progressive decline (p<0.05) with nadir on day 14, when they overlapped those in GHD, and then an increase on day 28, though persisting lower than in Ns, while GH levels did not vary during ICU stay. IGF-I levels were associated neither to burn extension nor to ROI score. On ICU day 1 pre-A, A and TRA levels were similar to those in Ns, but underwent a progressive decrease with nadir on day 7 (p<0.001) for pre-A and TRA, and later, on day 14 (p<0.05) for A; pre-A and TRA but not A showed a rebound increase (p<0.01) on day 14, though persistingly lower than in Ns. In conclusion, our present data firstly show the time course variation of IGF-I levels in burn patients as function of nutritional and hormonal variables. It has to be emphasized that in the most critical phase after burn injuries, IGF-1 levels are as low as in hypopituitary patients with severe GHD. The physiological basis which leads to the impairment of this endogenous anabolic drive in this phase is, however, not clear yet.

Adult↗

The role of quality control in a skin bank: tissue viability determination.

New surgical procedures requiring viable skin have increased rapidly over the last few years. The cell viability assessment in allograft skin is a major step forward in burn treatment, since it is well-known that taking is correlated with grafted tissue viability. Various methods, both qualitative and quantitative, are currently used. Although qualitative assays (histomorphology, immunocytochemistry) are routinely performed in our laboratory, there arose a need to set up a standardised quantitative assay in an attempt to obtain a cut-off value so that the skin sample could be determined valid or not for grafting. Therefore, two different tetrazolium salt compounds MTT and WST-1, were compared in order to determine their efficacy in the evaluation of tissue viability. Several experimental conditions were analysed: 1- cellular cultures of keratinocytes and fibroblasts, 2- fresh skin tissue samples, 3- the same specimen tested daily for at least 2 weeks, 4- after cryopreservation and thawing. Viable cells were analysed by the cleavage of tetrazolium salts to formazan by cellular enzymes. The formazan dye produced by metabolically active cells was then quantified by measuring the absorbance of the dye solution at the appropriate wavelength. It was seen that WST-1 is easier to handle, more stable, has a wider linear range, accelerated colour development and is more sensitive than MTT on fresh specimens and cell suspension. However, after 72 hours of storage at 4 degrees C, most of the WST-1 tested specimens no longer gave any absorbance signal, whilst MTT specimens were seen to give a signal for more than two weeks. Moreover, after thawing WST-1 tested samples were almost negative, whilst MTT samples continued to give strong signals. In conclusion, WST-1 assay offers rapid and precise results as to the cell viability of fresh allografts and cell cultures, whilst the MTT method is much more useful in establishing viability after long conservation and cryopreservation. In our clinical experience, allografts transplanted at 72 hr post-harvesting or after cryopreservation showed a mean of take more than of 80%, demonstrating that the MTT system is more reliable for the determination of allograft viability. Studies are ongoing with larger clinical cohorts to establish the precise cut-off value for skin graft validation.

Journal Article↗

The identification and characterization of hydrazinyl urea-based antibacterial agents through combinatorial chemistry.

An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.

Anti-Bacterial Agents↗

Splenectomy influences bone marrow infiltration in patients with splenic marginal zone cell lymphoma with or without villous lymphocytes.

BACKGROUND: Splenic marginal zone cell lymphoma (SMZL) is a low grade B-cell lymphoma in which patients can have circulating villous lymphocytes and can show a peculiar intrasinusoidal bone marrow (BM) infiltration. Splenectomy is the reported treatment of choice for these patients. The objective of this study was to evaluate the effects of splenectomy on patients with BM lymphomatous infiltration. METHODS: BM biopsies of 16 patients with SMZL were studied morphologically and immunohistochemically. In 12 patients, BM biopsies were taken before and after splenectomy. Four patients did not undergo splenectomy, and their BM biopsies were performed with an approximately 1 year interval. RESULTS: BM infiltration ranged from 10% to 40% of overall cellularity and was mostly of the intrasinusoidal type. After splenectomy, BM infiltration tended to become frankly nodular and showed an increase in tumor burden. Nonsplenectomized patients showed an unmodified picture. CONCLUSIONS: Splenectomy seems to induce important changes in patients with BM infiltration, probably through the lack of microenvironmental factors on circulating cells. These effects suggest reconsidering the role of splenectomy in the treatment of patients with SMZL.

Adult↗

Cyclin D1 gene contains a cryptic promoter that is functional in human cancer cells.

A novel cyclin D1 (CCND1)-TROP2 fusion oncogene has been isolated from human cancer cells. Unexpectedly, the chimeric cDNA was found to express TROP2 in the absence of exogenous promoters. Mutagenesis of the TROP2 and CCND1 sequences and in vitro transcription/translation show that a cryptic promoter is present in the 3' coding region of CCND1. The CCND1 cryptic promoter is functional in luciferase assays, where it augments the basal expression levels by eightfold and efficiently cooperates with an SV-40 enhancer. The transcription start sites of the cryptic promoter map at bases 797 and 935 of CCND1, as determined by RNase protection assays. The cryptic promoter possesses canonical binding sites for ubiquitous transcription factors and W/S, X1, and CAAT/Y boxes that are characteristic of major histocompatibility complex class II gene promoters. Remarkably, the cryptic CCND1 promoter is active in human cancer cells and generates a truncated transcript that contains CCND1 instability sequences. Thus, this novel CCND1 transcription unit may play a role in the regulation of the expression of cyclin D1 and in tumor cell growth.

3T3 Cells↗

Fig leaf tanning lotion and sun-related burns: case reports.

A sun tan is considered a symbol of well-being in our society, but incorrect methods of sun exposure can create serious problems. We present two cases of severe sun-related burns caused by fig leaf decoction used as home-made tanning lotion. Twenty four-thirty six hours after application and sun exposure, patients developed a phytophotodermatitis characterised by erythema, and blister formation involving all the photoexposed areas (45-70% BSA). Their general conditions became rapidly critical and they were admitted to our Burn Centre. The patients were discharged after 11 and 26 days, respectively. Haemolytic anaemia and retinal haemorrhages presented as systemic complications due to the furocoumarins present in the fig leaf decoction.

Administration, Cutaneous↗

Toxic epidermal necrolysis treated with intravenous high-dose immunoglobulins: our experience.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare severe acute exfoliative drug-induced skin disorder which has recently been ascribed to alterations in the control of keratinocyte apoptosis, mediated by an interaction between the cell surface death receptor Fas and its respective ligand. A therapeutic approach with intravenous immunoglobulins (IVIG) associated with pulse methylprednisolone, based on the inhibition of Fas-mediated keratinocyte death by naturally occurring Fas-blocking antibodies included in human immunoglobulin preparations, has produced good preliminary results. OBJECTIVE: To analyse the efficacy of IVIG in the treatment of TEN. PATIENTS: Nine patients with erythematous body surface area ranging from 38 to 85% and dermo-epidermal detachment from 4 to 37% were treated. RESULTS: Eight patients were healed and 1 died of septic shock and multiple organ failure. Interruption of further epidermal detachment occurred after an average of 4.8 days from the onset of IVIG therapy. Complete wound healing occurred after an average of 12 days. Concerning complications, 3 out of 8 surviving patients had acute respiratory failure requiring mechanical ventilation and 1 acute renal failure was treated with dialysis. Late sequelae were limited to dyschromia and nail dystrophies. No hypertrophic scars were observed. CONCLUSION: IVIG therapy represents a safe and valid approach for TEN.

Adult↗

Cutaneous innervation in hereditary sensory and autonomic neuropathy type IV.

The authors investigated immunocytochemically the innervation of a skin biopsy in a rare case of hereditary sensory and autonomic neuropathy type IV. A few protein gene product 9.5-, growth-associated protein 43-, calcitonin gene-related peptide-, and substance P-immunoreactive nerve fibers were observed in the deeper regions of the dermis. Neuropeptide Y-, nitric oxide-, and vasoactive intestinal polypeptide-immunoreactive fibers were completely absent. Their observations support the hypothesis that the sensory and autonomic defects reported in hereditary sensory and autonomic neuropathy are based on profound developmental alterations of the peripheral nervous system.

Calcitonin Gene-Related Peptide↗

Anterior tension-free repair of recurrent inguinal hernia under local anesthesia: a 7-year experience in a teaching hospital.

OBJECTIVE: To describe a 7-year experience with recurrent inguinal hernia repair performed mainly with tension-free mesh or plug technique under local anesthesia through the anterior approach, and to evaluate the safety and effectiveness of this method of treatment. METHODS: One hundred forty-five elective and 1 emergency herniorrhaphies for recurrent groin hernia were performed in 141 subjects (134 men and 7 women) with a mean age of 65 years (range 30-89). Concomitant medical and surgical problems were present in 73% and 8% of subjects, respectively. In 28 instances, the relapsed hernia had already been operated on once or twice for recurrence. A traditional hernioplasty had been previously performed in the vast majority of cases (136). Tension-free mesh or plug techniques through an anterior approach under local anesthesia were performed in 144 reoperations. Preperitoneal mesh repair and general or spinal anesthesia were used in all but one case when herniorrhaphy was performed during simultaneous operations. RESULTS: Mean hospital stay after surgery was 1.5 days (range 3 hours-14 days). No perioperative deaths occurred in this series. General complications were one case of acute intestinal bleeding and two cases of urinary retention. Local complications consisted of eight (5.5%) minor complications and one case of orchitis (0.7%) followed by testicular atrophy. In no instance was postoperative neuralgia or chronic pain reported. Two re-recurrences occurred. CONCLUSIONS: Given the low complication rate in this and other reported series and the absence of surgical or general complications described after preperitoneal open or laparoscopic repair and after general and spinal anesthesia, anterior mesh repair under local anesthesia seems to be a low-cost surgical technique that can be safely and effectively used even in a teaching hospital for the treatment of the majority of patients with recurrent groin hernias.

Adult↗

Functional analysis of T lymphocytes infiltrating the dermis and epidermis of post-burn hypertrophic scar tissues.

The cytokine profile of T cell clones (TCC) from the dermis and epidermis of burn patients with hypertrophic scars (HS) in active (AHS) and remission phases (RHS) was determined in this study. We found that AHS tissues are heavily infiltrated by Type 0-Type 1 polarized CD3+ lymphocytes producing high IFN-gamma and low IL-4 levels. Analysis of their surface marker phenotype showed that the high IFN-gamma production was shared equally between the CD4+ TCRalpha/beta and CD8+ TCRalpha/beta clones. The profile of TCC from RHS tissues revealed pronounced infiltration of Type 0-Type 1 polarized lymphocytes with an even more evident Type 1 profile. However, the levels of IFN-gamma produced by RHS-derived TCC were 4-6 times lower than those produced by AHS-derived TCC. These data show that high levels of IFN-gamma produced by Type 0-Type 1 lymphocytes infiltrating HS are a feature of AHS, whereas reduction of this ability to produce high levels of IFN-gamma, though without a shift towards a Type 0-Type 2 phenotype through an increase in IL-4, is characteristic of RHS.

Burns↗

Characterization of 12p molecular events outside ETV6 in complex karyotypes of acute myeloid malignancies.

Acute myeloid disorders with rearrangements of 12p outside the ETV6 gene were characterized by fluorescence in situ hybridization (FISH) with a panel of DNA probes. Seven patients with de novo acute myeloid leukaemia (AML), one with secondary acute myeloid leukaemia (sAML), and one in the blast phase of chronic myeloid leukaemia (CML-BP) were enrolled in the study. All AML cases showed multiple karyotypic changes. Chromosome 5 and/or 7 deletions were the most frequent accompanying changes. FISH revealed amplification, cryptic translocation, and fragmentation of chromosome 12, not discernible at karyotypic level. Different karyotypic rearrangements of 12p showed a common molecular event. Among the seven cases in which breakpoints could be determined, six were telomeric and one centromeric to ETV6. In three AML cases a new recurrent breakpoint in the telomeric region was identified distally to locus D12S158 and to pac 922B22 which is the most telomeric probe available for 12p. Accompanying cryptic deletions were also detected in five patients and the commonly deleted region, of around 700 kb, included the ETV6 gene and the D12S391 locus.

Adult↗

Expression and role of IL-15 in post-burn hypertrophic scars.

Hypertrophic scarring is a skin disorder that occurs after wounding and thermal injury. There is accumulating evidence that immunologic processes such as infiltration of activated T lymphocytes and altered cytokine production may play a role in the formation of hypertrophic scars. Interleukin-15, a cytokine identified as a T cell growth factor, also acts as a chemoattractant for T cells and has pro-inflammatory properties. We investigated the expression and the role of this cytokine in hypertrophic scarring. IL-15 expression was compared in skin biopsies of hypertrophic scars (HS) both in active (AHS) and in remission (RHS) phases, in normotrophic scars (NTS) and in normal skin using reverse transcriptase-polymerase chain reaction and immunohistochemistry. IL-15 expression in HS was significantly higher than in NTS or normal skin. Furthermore, AHS expressed higher levels of IL-15 than RHS. Immunohistologic analysis of AHS samples showed strong IL-15 immunoreactivity in keratinocytes and Langerhans cells in the epidermis and in macrophages, fibroblasts, and dermal dendritic cells in the dermis. High levels of IL-15 expression in AHS correlated with abundant infiltration of activated CD3+ cells. Ex vivo experiments indicate that IL-15 can sustain the proliferative response of T cells derived from AHS but not from RHS and NTS. In addition, IL-15 prevents both cytokine deprivation and activation-induced apoptosis of T cells derived from AHS. Taken together, these results suggest that IL-15 can be involved in the recruitment, proliferation, and apoptosis inhibition of T cells in AHS. The findings that the evolution from an AHS to a RHS is associated with a decrease in IL15 expression, and with a loss of IL-15 responsiveness in ex vivo-cultured T cells, indicate that this cytokine plays an important role in the biology of pathologic scar formation.

Adolescent↗

Cytogenetic analysis of hepatoblastoma: hypothesis of cytogenetic evolution in such tumors and results of a multicentric study.

Hepatoblastoma is a rare pediatric malignant tumor of the liver. Previous cytogenetic reports are sporadic. We karyotyped nine consecutive hepatoblastomas from the Italian centers participating in a multicentric study on hepatic tumors (SIOPEL 1). Six cases showed abnormal karyotypes. The most common abnormalities were trisomies of chromosomes 2 and 20. Four cases showed abnormalities of chromosome 1. On the basis of findings, we speculate the possibility of a cytogenetic evolutive pattern of hepatoblastomas.

Child, Preschool↗

Preoperative and intraoperative radioimmunodetection of cancer pretargeted by biotinylated monoclonal antibodies.

The in vivo post-targeting of tumor by means of anti-carcinoembryonic-antigen (CEA) monoclonal antibodies (MAbs) and the avidin-biotin three-step system was tested by immunoscintigraphy and radioimmunoguided surgery (RIGS) in six patients with primary or recurrent rectal cancer. The patients were preoperatively injected with 1 mg of FO23C5 (anti-CEA) and/or B72.3 anti-tumor-associated glycoprotein (TAG-72) biotinylated MAb; after 24 hours, 1 mg of avidin was administered, and, after a further 24 hours, biotin labeled to Indium-111 (In111) was injected. Preoperative imaging was obtained by means of a gamma camera, and a portable gamma-detecting probe (Neoprobe 1000) was intraoperatively used to count tumor and surrounding normal tissue. Eight tumor sites were localized in the six patients. Four lesions were identified preoperatively and six intraoperatively with a mean tumor-to-normal-tissue (T/NT) ratio of 1:8. This method allowed preoperative scintigraphy and intraoperative radioimmunodetection to be performed with a single radioactive compound injection of biotin labeled to In111 within few days before surgery.

Adult↗

Low IGF-I levels are often uncoupled with elevated GH levels in catabolic conditions.

Increased GH together with decreased IGF-I levels pointing to peripheral GH insensitivity in critically ill patients have been reported by some but not by other authors. To clarify whether elevated GH levels are coupled with low IGF-I levels in all catabolic conditions, basal GH and IGF-I levels were evaluated in patients with sepsis (SEP, no.=13; age [mean+/-SE]=59.2+/-1.2 yr), trauma (TRA, no.=16; age=42.3+/-3.4 yr), major burn (BUR, no.=26; age=52.8+/-4.2 yr) and post-surgical patients (SUR, no.=11; age=55.0+/-4.7 yr) 72 hours after ICU admission or after cardiac surgery. GH and IGF-I levels were also evaluated in normal subjects (NS, no.=75; age=44.0+/-1.5 yr), in adult hypopituitaric patients with severe GH deficiency (GHD, no.=54; age=44.8+/-2.3 yr), in patients with liver cirrhosis (LC, no.=12; age=50.4+/-2.8 yr) and in patients with anorexia nervosa (AN, no.=19; age=18.7+/-0.8 yr). Basal IGF-I and GH levels in GHD were lower than in NS (68.6+/-6.4 vs 200.9+/-8.7 microg/l and 0.3+/-0.1 vs 1.4+/-0.2 microg/l; p<0.01). On the other hand, AN and LC showed IGF-I levels (70.4+/-9.1 and 52.4+/-10.5 microg/l) similar to those in GHD while GH levels (10.0+/-2.8 and 7.9+/-2.1 microg/l) were higher than those in NS (p<0.01). IGF-I levels in SEP (84.5+/-8.8 microg/l) were similar to those in GHD, AN and LC and lower than those in NS (p<0.01). IGF-I levels in BUR (105.2+/-10.9 microg/l) were lower than in NS (p<0.01) but higher than those in GHD, AN, LC and SEP (p<0.01). On the other hand, in TRA (162.8+/-17.4 microg/l) and SUR (135.0+/-20.7 microg/l) IGF-I levels were lower but not significantly different from those in NS and clearly higher than those in GHD, AN, LC, SEP and BUR. Basal GH levels in SEP (0.6+/-0.2 microg/l), TRA (1.8+/-0.5 microg/l), SUR (2.2+/-0.5 microg/l) and BUR (2.2+/-0.5 microg/l) were similar to those in NS, higher (p<0.05) than those in GHD and lower (p<0.01) than those in AN and LC. In conclusion, our data demonstrate that low IGF-I levels are not always coupled with elevated GH levels in all catabolic conditions. Differently from cirrhotic and anorectic patients, in burned and septic patients GH levels are not elevated in spite of very low IGF-I levels similar to those in panhypopituitaric GHD patients. These findings suggest that in some catabolic conditions peripheral GH insensitivity and somatotrope insufficiency could be concomitantly present.

Adolescent↗

Primary ex vivo culture of keratinocytes isolated from hypertrophic scars as a means of biochemical characterization of CD36.

The CD36 antigen is a molecule which is ectopically expressed on epidermal keratinocytes of hypertrophic scars and is a good candidate for a marker for a broad range of skin pathologies. Most marker studies have been performed using immunohistochemical techniques on fixed skin sections. Our aim was to investigate the biochemical features of the CD36 expressed in pathological keratinocytes and to find an in vitro model for the study of the regulation of its expression. Here we show how keratinocytes isolated from hypertrophic scars can be cultivated in vitro and employed as a model for the study of these cells. We demonstrated that the antigenic features of the CD36 expressed on keratinocytes of hypertrophic scars are identical to those described for the CD36 expressed by other cell types. The molecule was expressed on the surface of keratinocytes which were non-adherent in vitro. Adherent and proliferating keratinocytes, as well as normal keratinocytes, were CD36 negative both at the surface and intracellularly. The in vitro proliferating cells from hypertrophic scars, but not the normal keratinocytes, showed intracellular expression of CD36 after long-term culture and cell stratification, suggesting a regulated expression of CD36 in pathological keratinocyte differentiation.

Adult↗