Biomedical subjects
Publications and source records attributed to M Piccirillo.
We describe the case of a 24 year old woman, affected by haemorrhagic shock due to post-partum uterine atony, who underwent an emergency hysterectomy with persistent postoperative bleeding, successfully treated with recombinant activated factor VII (Novoseven).
We describe a clinical case of a 7 year old girl, affected by peritonitis, septic shock and multiorgan failure, treated successfully with drotrecogin alpha associated with conventional therapy.
Proton magnetic resonance spectroscopy (1H-MRS) of the brain reveals specific biochemical information about cerebral metabolites, which may support clinical diagnoses and enhance the understanding of neurological disorders. The advantages of performing 1H-MRS at higher field strengths include better signal to noise ratio (SNR) and increased spectral, spatial and temporal resolution, allowing the acquisition of high quality, easily quantifiable spectra in acceptable imaging times. In addition to improved measurement precision of N-acetylaspartate, choline, creatine and myo-inositol, high-field systems allow the high-resolution measurement of other metabolites, such as glutamate, glutamine, gamma-aminobutyric acid, scyllo-inositol, aspartate, taurine, N-acetylaspartylglutamate, glucose and branched amino acids, thus extending the range of metabolic information. However, these advantages may be hampered by intrinsic field-dependent technical difficulties, such as decreased T2 signal, chemical shift dispersion errors, J-modulation anomalies, increased magnetic susceptibility, eddy current artifacts, limitations in the design of homogeneous and sensitive radiofrequency (RF) coils, magnetic field instability and safety issues. Several studies demonstrated that these limitations could be overcome, suggesting that the appropriate optimization of high-field 1H-MRS would expand the application in the fields of clinical research and diagnostic routine.
In the panorama of the numerous established cell lines, the human keratinocyte line HaCaT has a very interesting feature, having a close similarity in functional competence to normal keratinocytes. This cell line has been used in many studies as a paradigm for epidermal cells and therefore we selected HaCaT as a cell model for investigating the activity of three antitopoisomerase drugs (Camptothecin, Doxorubicin, Ciprofloxacin) on in vitro cell growth. The effect was evaluated both by a 24-h cytotoxicity test and by a 7-day antiproliferation assay, in which the cell viability was assessed by an MTT (3-(4,5-dimethyl-2-thiazolyl) 2,5-diphenil-2-H-tetrazolium bromide) test. DNA topoisomerase I was also partially purified from a nuclear extract of HaCaT cells, the level of topo I catalytic activity was measured by a pBR322 DNA relaxation assay and then the in vitro effect of antitopoisomerase drugs on the target enzyme was also assessed. The results indicated that the in vitro sensitivity of human epidermal HaCaT cells to antitopoisomerase drugs is comparable to that of many human tumour cell lines. HaCaT cells express a high level of topoisomerase I activity that is significantly inhibited by both Camptothecin and Doxorubicin and to a minor degree by Ciprofloxacin. A high correlation between the cell sensitivity to the antitopoisomerase I drug measured by the MTT test and the in vitro direct inhibition of HaCaT topoisomerase I was observed, suggesting that HaCaT cells can represent a very interesting model both for studying cellular pharmacokinetics of antineoplastic drugs on keratinocytes and for predicting possible secondary effects, exerted by these drugs on cutaneous cells, during treatment with chemotherapy.
Bone marrow stromal microenvironment is essential for the maintenance of the hematopoietic stem cell renewal both by cell-cell interaction and cytokine production. However, stromal cells also exhibit drug metabolizing activities and they may accumulate the drug and successively affect hematopoietic progenitors by a retarded release. Our study investigated the role of both primary culture of murine bone marrow stroma and established stromal cells (SR-4987) in modulating the "in vitro" toxic activity of Doxorubicin (DXR) against murine granulocyte-macrophage progenitors (CFU-GM). The main part of the study has been performed by a "in vitro" agar bilayer technique based on the CFU-GM assay performed over a feederlayer of stromal cells. The results suggest that bone marrow stromal cells play also an important role in decreasing the toxicity of Doxorubicin. Further SR-4987 stromal cells produce a Doxorubicin metabolite (not belonging to the series of metabolites described in literature) which is completely ineffective in inhibiting the growth of CFU-GM and the activity of topoisomerase I. Our data suggest that bone marrow stromal cells must be considered as a cell population having opposite pharmacological roles in modulating the drug toxicity on hematopoietic progenitors. In our model a mechanism of detoxification concerns the capacity of SR-4987 stromal cells to inactivate the drug. For a better prediction of drug hematotoxicity, it is very important to develop "in vitro" cell models able to discriminate between positive and negative modulation of drug toxicity that stromal cells can exert in the bone marrow microenvironment.
Explore the source record for details and available documents.
The CT-mediated signaling mechanisms have been widely used as a tool for helping the knowledge of the more complex mechanisms regulating cell growth and proliferation in which gangliosides are involved as receptors and cAMP as second messenger. In the present study we compare the susceptibility of two murine cell lines (SR-4987 stromal cells and L1210 leukemic cells) to inhibitory effect of cholera toxin (CT) on cell growth and correlate their sensitivity to CT with ganglioside content and intracellular cAMP accumulation. The results indicate a very different response of the two cell lines to CT treatment. L1210 cells (which contain GM1a ganglioside) are sensitive to the inhibiting activity of CT (IC50 in the clonogenic assay = 10(-9) M) but no cAMP accumulation was observed after the treatment. SR-4987 cells (which lack GM1a) show a dramatic increase of intracellular cAMP without any inhibition of cell growth following the CT treatment until 10(-8) M. However, after SR4987 cells have incorporated GM1a they became susceptible to CT (with a IC50 value = 10(-11) M). The comparison of these results with our previous studies on WEHI-3B leukemia cells confirms the remarkable heterogeneity of cell sensitivity to the growth inhibition by CT by emphasizing that this inhibition is the final event of very different mechanisms in which CT binding to a specific ganglioside seems to be necessary and sufficient whereas cAMP accumulation may not be coupled with the antiproliferative effect of CT.
The murine cell line SR-4987 was originated in our laboratory from adherent cells of a long term bone marrow culture. SR-4987 cells do not express p21-ras and c-fms products on membrane whereas secrete M-CSF, evidence a fibroblast-like morphology and are vimentine positive. This line shows a very poor "in vitro" agar clonogenicity which is not modulated by the addition of different cytokines and growth factors (M-CSF, GM-CSF, G-CSF, IL-3, IL-7, alpha-TNF, PDGF, and EGF). On the contrary, a dramatic increase in clonogenicity is observed in the presence of bFGF. The RT-PCR investigation evidences the mRNA encoding for bFGF, IL-7, GM-CSF, and SCF (c-kit ligand). The analysis of CD antigen expression on SR-4987 cell membrane indicates a phenotype (CD5+, CD44+, 45R(B220)+, sIg+, 5'-nucleotidase+) that is consistent with a B cell feature. Our observations suggest that exogenous bFGF might represent an appropriate stimulus for inducing the SR-4987 cells proliferation also in the absence of cell-substrate anchorage. Further, they indicate that SR-4987 cells could represent a particular differentiation stage in which characters of "stromal cell" and "B cell" are coexpressed in agreement with the hypothesis of a common stromal-hematopoietic differentiation.
BACKGROUND: The preferred method for creation of an ileoanal reservoir is still controversial. We prospectively studied the functional and physiologic outcome of our patients who underwent a double-stapled ileoanal reservoir (DSIAR). STUDY DESIGN: All consecutive patients who underwent restorative proctocolectomy with a DSIAR between 1988 and 1993 were evaluated. Functional results were assessed by questionnaires and anal manometry preoperatively and two, 12, and 24 months postoperatively. RESULTS: One hundred forty patients (90 males and 50 females) with a mean age of 40.7 (range, 12 to 71) years were evaluated. Of these, 107 patients (77 percent) had ulcerative colitis, 21 (15 percent) had familial adenomatous polyposis, six (4 percent) had indeterminate colitis, and six (4 percent) had a post-operative diagnosis of Crohn's disease. One hundred twenty-four (95 percent) of the 131 patients with closed stomas were available for functional and manometric evaluation at a mean follow-up period of 24 months. A 32 percent decline in the mean resting pressure (from 71.3 +/- 4 to 48.2 +/- 3.4 mm Hg) occurred early after DSIAR (p < 0.001) with partial recovery by 24 months. The maximal internal sphincter resting pressure showed a 39 percent decline (from 90.8 +/- 4.9 to 55.3 +/- 5.7 mm Hg, p < 0.005) with recovery after 12 months. There were no significant changes in the length of the high-pressure zone or mean or maximal squeeze pressures. A mean of 5.4 (two to 13) bowel movements occurred during the day and a mean of 1.2 (zero to four) occurred at night. Perfect or almost perfect continence was reported during the day and night, respectively, by 95 and 92 percent of the patients. Overall perioperative complications occurred in 30 patients (21 percent) including septic complications in eight (6 percent), and pouchitis in eight (6 percent). There was one postoperative death (0.7 percent). CONCLUSIONS: Double-stapled ileoanal reservoir is associated with good subjective functional and objective physiologic results and has acceptable rates of morbidity and mortality.
One of the technical difficulties during laparoscopic and laparoscopic-assisted resection of the right, transverse, and left colon is the mobilization of the splenic and hepatic flexures. We present a simple technique of colonoscopic traction of the splenic or hepatic flexure. This technique enables good exposure and facilitates dissection while laparoscopic mobilization of these segments of the colon is performed.
A porcine model was devised to investigate Doppler waveforms in dysfunctional renal allografts. NIH miniature pigs served as allografts donors and recipients. Renal transplantation was effected into the recipient pelvis while the left normotopic kidney was subjected to warm ischemia in order to induce acute tubular necrosis (ATN). Doppler demonstration of allograft arterial occlusion in six animals was confirmed at surgery. Increased pulsatility of intrarenal arterial signals constituted evidence of vascular rejection in two animals. Biopsies confirmed the diagnosis in both cases. Histologic changes of ATN were identified in two native kidneys subjected to ischemia. No waveform or pulsatility alterations were observed in these animals. The porcine model provides for the investigation of allograft Doppler waveforms in a controlled setting with free access to biopsy and operative pathologic correlation.
The sonographic findings and differential diagnoses of a wide spectrum of acute and chronic renal inflammatory processes are reviewed. These include focal and diffuse forms of bacterial nephritis, pyonephrosis, intra- and extrarenal abscess, renal tuberculosis and fungal infection, xanthogranulomatous pyelonephritis, and renal parenchymal malakoplakia. The role of ultrasound in the diagnostic and therapeutic management of patients with these diseases is discussed.
In addition to plain films and conventional excretory urography, ultrasound, computed tomography, and radionuclide scanning may contribute to the assessment of a wide spectrum of renal inflammatory diseases. This article discusses the role of contemporary imaging modalities in the diagnosis and management of patients with renal inflammatory lesions, including acute focal and diffuse bacterial infections, intra- and extrarenal abscess collections, pyonephrosis, xanthogranulomatous pyelonephritis, fungal infection, tuberculosis, and malakoplakia of the upper urinary tract.
Primiparous rats received 0.05, 0.25, 0.50, or 1.50 mg d-amphetamine/kg body weight, injected IP, when offspring reached 3-4 and 10-11 days of age. A multidimensional analysis of their maternal behavior revealed that at doses as low as 0.25 mg/kg, amphetamine had a disruptive effect on mother-pup intercontact interval, retrieval latency, inter-retrieval interval, number of pup retrieved and number of corners to which they were retrieved, time nest building, number of paper strips used, nursing time, time in motion, and number of squares entered. Disruption was dose-dependent for all the preceding except number of corners and time nest building. Amphetamine had no effect on the rate of maternal locomotion. The impact of amphetamine on nursing was significantly greater at pup ages of 3-4 days than at 10-11 days. Drug-induced augmentation of arousal exceeding optimal levels for adequate care-giving and locomotor stimulation incompatible with elements of maternal behavior may account for dose-dependent impairment in the range of 0.25 to 1.50 mg/kg d-amphetamine.
Selective CNS dopamine depletion was produced in neonatal female rats by administration of 6-hydroxydopamine and desmethylimipramine. These rats were subsequently tested as adults for maternal behavior toward their own offspring and received d-amphetamine prior to half of these sessions. The effects of early, selective CNS dopamine depletion and its related developmental disruptions on later care of offspring and response to amphetamine were thereby assessed. Pup retrieval, nest building, crouching, and locomotor behaviors were studied in 6-OHDA + DMI treated mothers while offspring were examined with respect to weight, density of fur, age of eye opening, and shuttlebox avoidance learning. Depletion of brain dopamine to 30% of control concentrations was associated with increased crouching time but with no other differences in caregiving, offspring development, or response to amphetamine. Although profound neonatal depletion of dopamine leads to a variety of disturbances in early life, later maternal behavior is adequate and apparently enhanced. The possible role of compensatory brain mechanisms is discussed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Fifty MR scans conducted at 1.5 T were evaluated to assess how well the pancreas could be identified. A total of 128 sets of images were reviewed. The pancreatic head was identified in 81%, 82% and 74% of scans with T1, intermediate and T2-weighting, respectively. The body was identified in 100%, 96% and 70% and tail in 96%, 87% and 54% on those respective sequences. Relative contrast was calculated between pancreas and: liver, spleen, muscle, fat, stomach and small bowel. The variability seen in contrast compared to stomach and small bowel suggests that consistent MR visualization of the pancreas will probably necessitate the use of an oral contrast agent.