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Biomedical subjects

M Ippolito

Publications and source records attributed to M Ippolito.

13 recordsLinked to original sources

High fat fed hamster, a unique animal model for treatment of diabetic dyslipidemia with peroxisome proliferator activated receptor alpha selective agonists.

Dyslipidemia, a major risk factor for cardiovascular disease, may be directly linked to diabetic hyperglycemia and insulin resistance. An appropriate dyslipidemic animal model that has diabetes would provide an important tool for research on the treatment of diabetic dyslipidemia. Ten days of high fat feeding in golden Syrian hamsters resulted in a significant increase in insulin resistance and baseline serum lipid levels accompanied by a pronounced dyslipidemia. Thirteen days of treatment with fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARalpha) selective agonist, produced a dose-dependent decrease in serum lipid levels. The pattern observed was characterized by lowered very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) and raised high-density lipoprotein (HDL) cholesterol in a fashion similar to that seen in man. Diabetic conditions were also significantly improved by fenofibrate with a normalization of impaired glucose tolerance and an improvement of insulin sensitivity during an oral glucose tolerance test. These data suggest that fenofibrate may correct not only the dyslipidemia but also the insulin resistance caused by a high fat diet, and the high fat fed hamster may be a good animal model for research on the treatment of diabetic dyslipidemia with PPARalpha selective agonists.

Animals↗

PPARalpha agonists reduce 11beta-hydroxysteroid dehydrogenase type 1 in the liver.

11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is an enzyme that converts cortisone to the active glucocorticoid, cortisol. Cortisol-cortisone interconversion plays a key role in the regulation of glucose metabolism, since mice deficient in 11betaHSD1 are resistant to diet-induced hyperglycemia. Peroxisome proliferator activator receptors (PPAR) are key regulators of glucose and lipid homeostasis. We observed a striking downregulation of murine hepatic 11betaHSD1 expression and activity after chronic treatment of wild-type mice with PPARalpha agonists, while 11betaHSD1 in the livers of PPARalpha knockout mice, or in mice treated for only 7 h with PPARalpha agonists, was unaltered. Our results are the first to show PPARalpha agonists can affect glucocorticoid metabolism in the liver by altering 11betaHSD1 expression after chronic treatment. Regulation of active glucocorticoid levels in the liver by PPARalpha agonists may in turn affect glucose metabolism, consistent with reports of their antidiabetic effects.

11-beta-Hydroxysteroid Dehydrogenases↗

Lack of prognostic value of 99mTc MIBI rest, 18F FDG and 201TL rest/redistribution on PTCA outcome of patients with moderate left ventricle dysfunction.

BACKGROUND: The clinical work-out of patients undergoing coronary revascularization includes the assessment of myocardial viability. This approach has to be defined in the different classes of patients. The aim of this study was to evaluate the predictive prognostic value of different techniques on outcome following PTCA in patients with moderate left ventricle dysfunction (left ventricle EF > or = 40%). METHODS: Seventeen patients with EF > or = 40% and undergoing PTCA were studied by 201Tl rest/redistribution, 18F-FDG and 99mTc-MIBI rest. Regional kinesis was scored by echo, dividing left ventricle in 11 segments. The echo evaluation was repeated at 1 and 6 months after revascularization. RESULTS: Global EF was 52.5 +/- 7% and 69 segments had abnormal kinesis. Patients underwent stress/rest 99mTc-MIBI SPET, rest/redistribution 201Tl SPET and rest 18F-FDG PET. Among the 11 segments defined on echo-matched tomographic images, the one with the highest activity at stress was assumed as reference (activity = 100%). If > 50% of reference segment, 18F-FDG and 201Tl uptakes were considered significant. After PTCA, the echo-follow-up did not demonstrated significant improvement of left ventricle function at 30 days after PTCA (EF 56 +/- 6%) as well as at 6 months (EF 56 +/- 9%). The positive predictive value under these conditions resulted: 46.5% with 99mTc-MIBI rest, 47.4% with 201Tl rest-redistribution and 45.7% with 18F-FDG. CONCLUSIONS: In summary, in the class of patients with moderately compromised function, considering as reference the improved regional kinesis after PTCA, 99mTc-MIBI at rest, 201Tl rest/redistribution and 18F-FDG do not exhibit a clear predictive value; patient population is then a highly relevant point to establish the accuracy of these diagnostic procedures.

Adult↗

Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study.

Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly one to three times weekly) was given for < or = 56 months to 38 patients with malignant gliomas. There was minimal or no toxicity. Twenty of 30 patients (66%) receiving at least twice weekly poly-ICLC showed regression or stabilization of gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median = 65% volume decrease). All but one patient with anaplastic astrocytomas who received continuous poly-ICLC remain alive, with a median progression-free survival of 54 months from diagnosis. Median Kaplan-Meier survival is 19 months for patients with glioblastomas who receive at least twice weekly poly-ICLC treatments. Tumor response was associated with 2',5' -oligoadenylate synthetase activation (P = 0.03) but not with serum interferon. We hypothesize clinical activation by poly-ICLC of a basic host tumor suppressor system. Prolonged, quality survival with tumor stabilization or regression confirmed by magnetic resonance imaging for most patients with anaplastic astrocytomas and glioblastomas suggests that more extensive laboratory and controlled clinical studies are warranted. The concept of long-term, broad spectrum stimulation of host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such as low-dose poly-ICLC, may be applicable to the treatment of other malignancies.

Adult↗

[Autologous blood collection in pregnancy. Prospective study].

Autologous blood predonation during pregnancy, with the aim of autotransfusion after delivery, has gained increasing consensus over the last few years. However, there are still some controversial aspects. In particular, the cost/benefit ratio of institutionalizing the above mentioned practice would appear altogether unfavourable (too many women would be really in need of transfusion after delivery). The aim of the present study is to assess the results of our experience using autotransfusion in obstetrics. This longitudinal and prospective study was carried out on a sample of 29 pregnant women who donated 1 unit of blood during the last month of their pregnancy. Phlebotomy was preceded by a verification of the permitting conditions (Hb > or = 11 g/dl; Ht > or = 33%). Before, during and after phlebotomy, the patients underwent cardiotocographic monitoring and periodic observation of vital parameters. The hematologic parameters registered during the various test (before predeposit, before delivery, in puerpery) were statistically analysed. The hemochromo values appeared satisfactory in all cases at the time of admittance for labour. As a consequence of a hematic loss higher than usual at the moment of delivery, in many cases the hemoglobin values during puerpery did not enable us to exclude a priori the advisability of a transfusion. From the study we see how the cost/benefit ratio of the predeposit practice in obstetrics is less unfavourable than commonly thought.

Adult↗

[Fetal megalosomia: clinical and prognostic value of main risk factors].

Fetal megalosomia associates with an increased risk of maternal and perinatal pathology. However it is right to make a clear distinction between "physiologic" megalosomia, expression of a high genetic potential of growth from the fetus, and megalosomia referable to any maternal pathology. While the first one entails problems of obstetric management at the most, the second one compels to take measures in order to reduce its incidence. A sample of 45 fetuses with megalosomia was studied retrospectively and compared with a standard sample, randomly selected among the fetuses, term delivered, who in the same period considered (January 1990-January 1994) weighed less than 4 kg at birth. This was done in order to verify which of the risk factors of fetal megalosomia reported in the medical literature affects the most the people who address our Institute. Important risk factors resulted, besides maternal height and postdatism, pre-gestational overweight and obesity. The prognostic significance of the factors, such as advanced maternal age, multiparity, male sex of the unborn child, excessive maternal weight gain during pregnancy, previous megalosomia, was of more difficult interpretation. In our experience, gestational diabetes didn't play the role, universally recognized to it, of the most important risk factor of fetal megalosomia.

Female↗

[Autologous transfusion in obstetrics and fetal safety].

It is common knowledge that for modern medicine transfusion therapy represents a precious resource and an often mandatory option. It is equally known that autohemotransfusion (or autologous transfusion) provides further advantages: certainty of blood availability when necessary, absence of transfusion reactions, elimination of the risk of infections that is still associated with the traditional homologous transfusions. In its most widespread application, autotransfusion provides for the donation of one or more units of autologous blood, mostly before elective surgery. Even in obstetrics the practice of autologous blood donation with the aim of autotransfusion is finding increasing employment. However, there are still controversial aspects and the need is pointed out for more authoritative verifications as refers to the alleged innocuity to the fetus of acute maternal blood loss. The present study was performed to contribute personal experience to a better definition of the possible interactions between autologous blood donation during pregnancy and unborn child welfare. To this end, 80 term pregnant women underwent fetal heart rate electronic monitoring before, during and after the donation of one unit of autologous blood. Both during and after the phlebotomy there were no cardiotocographic signs of fetal hypo-oxygenation. Even the non stress tests performed at a distance of 24 hours and those that were periodically repeated afterwards were normal, confirming the safety of autologous predonation during pregnancy. However, the authors think that in obstetrics it is still premature to consider the experimental phase of autotransfusion as definitively exhausted.

Blood Donors↗

[Correction measured by attenuation in tomographic heart studies with single photon emission with thallium 201. Comparison with positron- emission tomographic studies with ammonium marked with nitrogen].

PURPOSE: We investigated 201Tl myocardial uptake with(out) nonuniform attenuation compensation in ischemic myocardiopathy patients. The segmental patterns of the two types of SPECT images were compared with PET [13N]NH3 studies performed in the same patient. PET images were taken as reference and the diagnostic accuracy of SPECT with(out) attenuation correction was evaluated. MATERIAL AND METHODS: During the SPECT study transmission and emission data were simultaneously recorded by a triple head gamma camera equipped with fan beam collimators and a 99mTc transmission line source (740MBq). SPECT and PET images, the former reconstructed with(out) attenuation correction, were corecorded and reoriented along the short axis. The left ventricular wall was divided into 11 segments and segmental activity normalized to maximum in each study. RESULTS: Statistically significant differences were found between PET/(un)corrected SPECT ratios in posterior and septal segments. In these myocardial regions, attenuation correction compensates for attenuation artifacts, by correcting the underestimation of radioactivity concentration caused by radiation absorption. A statistically significant difference was also found in midventricular anterior and apical segments (p < .05). However, in these regions attenuation correction results in a decrease in corrected relative to uncorrected SPECT activity. The agreement rate with PET data is higher for corrected SPECT (mean differences were 3.12 +/- 11.51 and 2.19 +/- 8.63 for uncorrected versus corrected SPET). We had 50% positive and 77% negative predictive value without attenuation correction, versus up to 69% and 90%, respectively, with attenuation correction. CONCLUSIONS: The attenuation correction procedure with simultaneous transmission-emission effectively reduces attenuation artifacts in SPECT myocardial imaging. While diagnostic accuracy increases in posterior and septal myocardial regions, anterior and apical data need careful interpretation because a relative decrease in radioactivity concentration can be observed after attenuation correction.

Adult↗

[Current trends and future perspectives in the therapy of the osteoporosis].

Osteoporosis is a pathology of considerable social impact for its high frequency in the elderly and for serious complications of the fragility fracture. Osteoporosis prevention requires high bone mass peak during growth age, adult and elder people must limit the bone loss by taking specific daily behavior and nutritional measures. The pharmacological treatment is based on drugs which are able to change bone metabolism, among which the bisphosphonates result to have a good efficacy with few collateral effects, the last generation (Alendronate and Risedronate) may be taken once a week. Promising for the next future is the Recombinante Parathormon, recently approved from the Food and Drug Administration for osteoporosis treatment. Leptin and l'Osteoprogerin are new experimental molecules under study able to act on the mechanism of central and local regulation of bone remodeling.

Bone Remodeling↗

[Chronic osteomyelitis: one-step treatment].

PURPOSE: Chronic osteomyelitis is a surgical disease that require significant dedication from surgeons to eradicate. Osteomyelitis can result from a variety of etiologies but most often is a consequence of trauma (open fractures) to a long bone. This type includes osteomyelitis secondary to a contiguous focus of infection (after trauma and its surgical treatment: osteosynthesis). Here we are reporting one case of post-traumatic chronic osteomyelitis of the humerus. PATIENTS AND METHODS: A 34-years-old man presented with a post-traumatic chronic osteomyelitis due to an open fractur of the diaphysis humerus. We proposed a one-step surgical treatment, including fistulectomy, sequestrectomy, opening of the proximal and distal intramedullary canal. Antimicrobial therapy should be followed by close observation and treatment with appropriate antibiotics. RESULTS: A clinical control at 30 days from the intervention revealed that: no secretion; negative cultured exam; second-intention healing of the skin. CONCLUSIONS: Treatment requires isolation of the pathogens, significant debridement for removal of all infective and necrotic material, both of bone origin and soft-tissue one. Is is necessary not to close the foci: in this way we leave an external drainage, which is able to provide a tissues sterilization by secretion drainage and by the effects of the systemic antimicrobial therapy. Our results indicate that this long-term problem can be solved by a one-stage procedure that provide spontaneous second- healing of the skin defects, excluding the bony and soft tissue reconstruction.

Adult↗