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Biomedical subjects

F Morelli

Publications and source records attributed to F Morelli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Autoapheresis and intraoperative blood salvage in oncologic surgery.

Transfusion of predeposit or salvaged autologous blood has continued to grow since the 1980s. Issues such as the indications for use and cost effectiveness as well as the safety of autologous blood salvaged during cancer surgery have emerged and should be addressed. The concern for possible contamination of autologous RBC with cancer cells responsible for metastasis has limited the use of autologous salvaged blood in cancer patients. Nevertheless, clinical experience has been gained on the use of salvaged blood in patients with colorectal, gastric, renal, hepatic, breast, bladder and lung cancer. No evidence has been reported showing an increase in metastasis or a decrease in patient survival, in spite of the obvious demonstration that salvaged blood is contaminated with viable tumor cells which are not washed out of the RBC layer during intraoperative blood salvage (IOBS). However, a number of limitations have hampered the widespread use of IOBS in these patients and the technique is not well established. Increasing knowledge of the deleterious effects of allogeneic blood transfusion both in terms of the increased number of viral or bacterial infections and the down-regulation of the patient's immune system have recalled attention to IOBS and to the techniques such as filtration, which might reduce the risk of reinfusion of cancer cells, or totally eliminate the risks such as irradiation has been proposed by Hansen's group. This paper reviews the topic with some emphasis on our personal experience with gamma and X-ray irradiation of salvaged blood in a large reference hospital, where IOBS and filtration of salvaged blood were established for use in cancer patients in 1993 and 1996.

Blood↗
PubMed1999

Multiplex semi-quantitative reverse transcriptase-polymerase chain reaction of low abundance neuronal mRNAs.

The sequential use of reverse transcriptase and the polymerase chain reaction (RT-PCR) has provided molecular biology research with an exquisitely sensitive and fast technique for studying gene expression. This method is particularly useful to study transcripts in the nervous system, which are on average present at low levels and the amount of tissue or cells to be analyzed is often limited. Here, we describe a RT-PCR assay which allows the simultaneous detection and semi-quantitation of several transcripts (multiplex). Multiple PCR primer pairs are used to detect different target transcripts in a single reaction, together with a pair of primers able to amplify the hypoxantine-phosphoribosyl-transferase (HPRT), a gene constitutively expressed at low levels throughout the nervous system. HPRT levels remain constant also during neurogenesis and it is thus apt to be used in developmental neurobiology. This internal standard is the mRNA of reference to evaluate sample variation in RT and PCR reactions and to monitor the degradation and recovery of RNAs. Normalization with respect to HPRT cDNA allows to estimate the relative abundance of each target mRNA.

Animals↗
PubMed1999

Porin from Pseudomonas aeruginosa induces apoptosis in an epithelial cell line derived from rat seminal vesicles.

Micromolar concentrations of porin, purified from the outer membranes of Pseudomonas aeruginosa, induced in vitro the classic morphological and biochemical signs of apoptosis in an epithelial cell line (SVC1) derived from the rat seminal vesicle secretory epithelium. The programmed cell death (PCD) was p53 independent and associated with significant decrease of bcl-2 expression, a marked increase of c-myc transcriptional activity, and an absence of the mRNA coding for tissue transglutaminase. The Ca(2+) influx, caused by the porin treatment of SVC1 cells, appears to play an important role in the triggering of apoptosis in our biological model. The possibility that the porin property of inducing PCD plays a role in the infertility of individuals chronically infected by gram-negative bacteria is discussed.

Animals↗
PubMed1999

Multicomponent collection (MCC) with the latest hemapheresis apparatuses.

BACKGROUND: Collection of multiple products including plasma, packed red blood cells (PBRC) and double units of platelets, is increasingly improving donor utilisation and decreasing blood transfusion costs. Total apheresis is the new trend in blood banking and both industry and physicians are progressively expanding their involvement in this field. During 1998, at our hemapheresis unit, we used three new apparatuses for multicomponent collection (MCC). These apparatuses vary in terms of principle, operation and specific capabilities, and thus knowledge of them is essential to match their characteristics with plateletapheresis needs. STUDY DESIGN: We reviewed all MCCs carried out in 1998 with MCS+, Trima and Excel-Pro cell separators. These apparatuses were evaluated in terms of platelet yield, white blood cell (WBC) contamination, efficiency per minute, platelet activation, and PBRC product quality. RESULTS: The three machines are compared in the following table [table in text]. CONCLUSIONS: MCC with the new apparatuses is well accepted by donors and personnel. There are no risks for the donors and, excluding ACD reactions and/or vaso/vagal attacks at the beginning of procedures, no severe reaction was seen. The quality and quantity of platelet products are good. When PRBC or a second platelets unit are collected, the cost of the kit is covered by this double product.

Blood Component Removal↗
PubMed1998

[Case series of mesotheliomas from hospital archives as contribution to preventive intervention].

The clinical charts of 18 patients in the departments of radiotherapy and oncology of the hospital "Casa Sollievo della Sofferenza" (San Giovanni Rotondo, Italy) from 1993 to August 1998, were reviewed. Each case was assigned to first (fine needle aspiration, cytologic exam), second (multiple biopsies during thoracoscopy or laparoscopy) or third (operation) diagnostic level and asbestos exposure was analysed. The age-group was between 21 and 76 years (median 57 years). Three patients were less than 30 years old. The ratio M:F was 17:1. Malignant mesotheliomas were histologically confirmed in 16 cases: 1 patient was classified as malignant pleural tumor (cytology and CT scan), 1 patient as suspicious malignant pleural tumor (only radiological diagnosis) and both were excluded for analysis. We observed 1 case in 1993, 2 in 1994, 3 in 1995, 3 in 1996, 5 in 1997, 2 up to August 1998. Second level diagnosis was assigned to 9 patients and third level to 7 patients. In 9 out 16 cases (56%) the exposure was occupational: 5 ascertained, 2 probable, 2 possible.

Adult↗
PubMed1997

Hepatitis C virus genotypes in liver transplant recipients: impact on posttransplant recurrence, infections, response to interferon-alpha therapy and outcome.

BACKGROUND: End-stage liver disease due to hepatitis C virus (HCV) is the most common indication for liver transplantation in U.S. veterans. We investigated the influence of HCV genotypes on the incidence and timing of recurrent HCV hepatitis, survival, infectious morbidity, and response to interferon-alpha therapy in this unique patient population. METHODS: HCV genotype was determined by direct sequencing of the NS5 region of HCV with type-specific primers. RESULTS: Genotype 1a (66%, 32/47) was the predominant genotype. Type 1b was found in 25% (12/47) of patients and type 2b was found in 9% (4/47). Histopathologically recurrent HCV hepatitis developed in 53% (25/47) of the patients after transplantation. This group included 45% (14/31) of the patients with type 1a, 67% (8/12) of the patients with type 1b, and 25% (1/4) of the patients with type 2b (P>0.5). The time to recurrence and the severity of HCV recurrence as defined by aminotransferase levels or Knodell scores were not different among the three genotypes. There was a trend toward a higher incidence of major infections in patients with type 1b (75%) versus type 1a (48%) and type 2b (50%) (P=0.11). The response to interferon-a therapy did not differ significantly among the genotypes. Mortality at 5 years was 16% (5/31) in patients with genotype 1a, 42% (5/12) in patients with genotype 1b, and 50% (2/4) in patients with genotype 2b (P=0.06). CONCLUSIONS: The incidence, time to recurrence, and response to interferon-alpha therapy did not differ between the various genotypes in our liver transplant recipients. However, there was a trend toward higher infectious morbidity and overall mortality in patients with genotype 1b after transplantation.

Adult↗
PubMed1996

Hepatic Retransplantation--an analysis of risk factors associated with outcome.

Hepatic retransplantation is controversial because the results are inferior to primary transplants and organs are so scarce. To determine the factors that are associated with poor outcome within the first year following retransplantation, we performed a multivariate analysis, using stepwise logistic regression, of 418 hepatic retransplantations performed at a single institution from November 1987 to December 1993. The minimum follow-up was 1 year. Seven variables were found to be independently associated with subsequent graft failure (defined as either patient death or retransplantation): donor age (odds ratio 2.2 for each 10-year increase over age 45, 95% CI 1.3 to 3.7), female donor sex (odds ratio 1.7, 95% CI 1.05 to 2.7), recipient age (odds ratio 1.6 for each 10-year increase over age 45,95% CI 1.2 to 2.8), need for preoperative mechanical ventilation (odds ratio 1.8, 95% CI 1.1 to 2.9), pretransplant serum creatinine (odds ratio 1.24 for each increase of 1 mg/dl, 95% CI 1.1 to 1.4), pretransplant total serum bilirubin (odds ratio 1.4 for each 10-mg/dl increase over 15 mg/dl, 95% CI 1.1 to 1.8), and the primary immunosuppressant, using tacrolimus as the reference category (odds ratio for cyclosporine-based immunosuppression 3.9, 95% CI 2.3 to 6.8). Although not part of the logistic regression model, the timing of retransplantation was also found to be important, with the overall probability of failure increasing from 0.58 on day 0 to a peak of 0.8 on day 38 and decreasing slowly after that. The implications of these results regarding the appropriateness of retransplantation are discussed.

Adult↗
PubMed1996

Early upregulation of medium neurofilament gene expression in developing spinal cord of the wobbler mouse mutant.

Homozygous wobbler mouse mutants develop a progressive paralysis due to spinal motoneuron degeneration. To understand the molecular aspect underlying the genetic defect we have studied the embryonic (from E13) and postnatal expression of the three neurofilament and choline acetyltransferase genes in each member from several wild-type (wt) and wobbler (wr) progenies. There are no variations among wt littermates at all ages studied. In contrast, analyses of neurofilament mRNA reveals a 3-4-fold increase of medium neurofilament (NFM) mRNA in wobbler mice (wr/wr). The pattern of increased NFM mRNA during development, prior to the appearance of the wobbler phenotype, among littermates (from heterozygous carriers) conforms to a mendelian inheritance of a single gene defect 1:2:1 (wr/wr:wr/+:+/+). Light and heavy neurofilament mRNA levels are also increased later in development exclusively in those individuals with high NFM mRNA values indicating that increase of the latter is associated with increase of the light and heavy subunit expression. Also NF proteins are increased. Expression of choline acetyltransferase gene is instead always comparable to normal control. Our study provides novel insights into the nature of the wobbler defect, strengthening the hypothesis that neurofilament accumulation plays a pivotal role in the etiopathogenesis of motoneuron degeneration.

Animals↗
PubMed1996

Assessing risk in liver transplantation. Special reference to the significance of a positive cytotoxic crossmatch.

OBJECTIVE: The authors determined the impact of a positive cytotoxic crossmatch on the outcome of liver transplantation. SUMMARY BACKGROUND DATA: Liver allografts rarely undergo hyperacute rejection, but transplants performed across a positive cytotoxic crossmatch tend to follow a different clinical course, with higher intraoperative blood use, postoperative graft dysfunction, and, in some cases, graft loss. How this affects overall graft survival has not been determined. METHODS: The authors provide a retrospective analysis of 1520 liver transplants performed between November 1989 and December 1993, with a minimum follow-up of 1 year. All cases had a cytotoxic crossmatch using serum pretreated with dithiothreitol. RESULTS: There were 1390 negative crossmatch and 130 positive crossmatch cases. There was no difference in overall graft survival, although early survival rates were lower in the positive crossmatch group, with the maximum difference at 6 months: 0.76 (95% confidence interval, 0.74-0.78) for a negative crossmatch versus 0.68 (95% confidence interval, 0.61-0.77) for a positive crossmatch. These differences become negligible by the 2-year mark. Using stepwise logistic regression, the authors identified seven variables independently associated with outcome: 1) donor age, 2) donor gender, 3) prior liver transplant, 4) medical urgency status, 5) ischemia time, 6) indication for transplantation, and 7) primary immunosuppressant. CONCLUSIONS: The cytotoxic crossmatch is not statistically associated with overall graft survival after liver transplantation. However, early failure rates are higher in the positive crossmatch cases, a difference that disappears by the second year.

Adult↗
PubMed1996

Risk factors and predictive indexes of early graft failure in liver transplantation.

A retrospective analysis of 462 consecutive liver transplantations has been carried out. These were divided into two groups, according to whether they failed within 90 days (Group I) or survived longer than 90 days (Group II). Twenty-five donor and recipient variables were analyzed. In the univariate analysis, the only donor variable that was significantly different between the two groups was age (45.3 +/- 16.9 years in Group I vs 37.9 +/- 15.4 years in Group II, p < 0.001). There were five recipient variables significantly associated with early graft failure: history of previous liver transplantations (p < 0.0001), United Network for Organ Sharing 4 status (p = 0.003), primary diagnosis (p = 0.001), preoperative serum creatinine (1.97 +/- 1.5 mg/dL in Group I vs 1.46 +/- 1.2 mg/dL in Group II, p = 0.005), and preoperative total serum bilirubin (13.5 +/- 14.4 mg/dL in Group I vs 8.4 +/- 11.4 mg/dL in Group II, p = 0.003). In the multivariate analysis, only three variables were independently associated with outcome: donor age greater than 45 years, abnormal (> 1.5 mg/dL) recipient preoperative creatinine, and a history of previous liver transplantation.

Adult↗
PubMed1995

Chronobiometric identification of disorders of hunger sensation in essential obesity: therapeutic effects of dexfenfluramine.

In human beings, hunger is a proprioceptive signal that shows intraday (circadian components) and within-day (ultradian components) recursivity. Both periodic components can be investigated by chronobiometric procedures by combining the Cosinor method with spectral analysis. A 24-hour profile of hunger sensation (HS) can be plotted on a 1-to-10 scale of intensity using self-rated scores performed every half-hour of the day. Circadian and ultradian components were studied in 60 patients affected by essential obesity (20 men and 40 women; mean age, 38.4 years; mean body weight, 101 kg) before and after treatment with dexfenfluramine (Isomeride; Servier, Orléans, France) 15 mg orally twice daily, for 30 days. The control group consisted of 30 clinically healthy subjects (15 men and 15 women; mean age, 37.5 years; mean body weight, 69 kg). Chronobiometric analysis shows three patterns in obese patients, which suggests that HS may be normal (eurectic obesity), exaggerated (hyperrectic obesity), or diminished (hyporectic obesity). After dexfenfluramine administration, HS was showed a substantial decrease in the daily mean level. The spectrum of resolution in circadian and ultradian components was found to be maintained in eurectic obesity and partially readjusted in hyperrectic and hyporectic obesities. This demonstrates that dexfenfluramine acts not only as an anorectic but also as a chronizer by interfering with the recursive components of HS. The anorectic and chronizing effects suggest that dexfenfluramine is a "chronoanorectic drug" that interacts with the chronobiologic properties of the serotoninergic system.

Adult↗
PubMed1995

Intraoperative blood salvage (IOBS) in cardiac and vascular surgery.

The extensive application of IOBS has permitted a great reduction in the use of homoglous transfusion which presently represents the largest field of application of autologous systems. In cardiac and vascular surgery, IOBS is particularly useful to the goal of preventing the transmission of viral disorders and other adverse effects related to homologous transfusions. The apparatuses for IOBS may also be used to perform hemodilution and sequestration of a desired amount of platelet rich plasma. The appropriate usage of drugs in perioperative period and the promotion of hemostasis with IOBS are important costituents for the correct transfusional management of the patient. The feasibility and safety of IOBS is known and in expert hands it is an optimal method for the transfusional treatment of surgical patients.

Blood Transfusion, Autologous↗
PubMed1995

[Osteoporosis and densitometry screening: preliminary results].

We have examined the bone densitometry with osteoradiometer (ORM) of 355 patients who came to the "Centre for Prevention, Diagnosis and Therapy of Osteoporosis" at the Israelitic Hospital of Rome. 144 patients, 141 females and 3 males, will be studied in the future because their densitometric values are lower than the values considered normal for age and sex. We have valued anamnestic data (age, menopause, pregnancies, excessive use of alcohol and smoke, sedentary habits), medical data hyperthyroidism, OCB, chronic diarrhoea) and surgical data (ovariectomy, thyroidectomy, gastro-duodenal resection, mastectomy) to have the correct outline of the patient situation before further researches and beginning the best medical therapy. For the prevention and screening of people "at risk" densitometry is irreplaceable both pre-clinical osteopeny, and for checking the effects of the therapy.

Adult↗
PubMed1995

Preparation and storage in Plasma-Lyte A of platelets collected with the cell separator CS3000 Plus equipped with the PLT30-separation and TNX6 collection chambers.

The last five years have been characterized by the presentation of new cell separators the main task of which is the collection of high yield-high quality platelets. The CS3000 is an old apparatus which has undergone rejuvenation to sustain the assault of its new competitors. The CS3000 Plus Omnix system is the latest version to be offered along with a combination of TNX-6 separation/PLT30 collection chambers for optimal platelet collection. In this paper we present our results with this apparatus and configuration after its adaptation to the collection and storage of platelets in a non-plasma medium, the Baxter Plasma-Lyte A. After separation the platelet product (PC) was left in the collection chamber and resuspended with 200 ml of Plasma-Lyte A instead of being resuspended in autologous plasma as usual. Plasma was collected in a separate bag (400-450 ml) for transfusion or fractionation purposes. PC quality was assessed by evaluating the platelet yield (4.17 +/- 1.8 x 10(11), and the WBC contamination (4.8 +/- 2.6 x 10(5)). The presence of platelet aggregates (platelet count after aggregate fixation with formalin/platelet count after disaggregation in EDTA), the aggregation induced by ADP, collagen and ristocetin, the hypotonic shock response and the stability of membrane glycoproteins (CD 62 - 62 - 63 - 36- 42b - 51) were measured in the preapheresis samples and in the PC immediately after, 24 and 72 hours after collection. These results were totally satisfactory as was the post-transfusion survival measured as corrected count increment in 10 transfusions to non refractory patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1993

Two functionally different glutamate receptors of the kainate subtype in embryonic rat mesencephalic cells.

The amino acid glutamate is a widespread excitatory neurotransmitter in the brain. It activates cation-selective channels expressed by nearly every neuron and by glial cells; also various second messenger cascades. Little is known about the ontogeny of glutamate neurotransmission during neurogenesis. We have analyzed the development and differentiation of excitatory amino acid responses and Na+ channels in cells dissociated from embryonic rat ventral mesencephalon and striatum as well as cortex and cerebellum using fluorescent voltage-sensitive oxonol dyes and flow cytometry. Analysis of fluorescence distribution revealed complex profiles under resting conditions which changed in a characteristic manner over the period studied (Embryonic (E) Days 12-20). The response to the Na+ channel agonist veratridine appeared at E12/13 in the mesencephalon. At E13 L-glutamate and kainate evoked changes in membrane potential interpreted as cellular hyperpolarization. At E15 some cells still responded by hyperpolarizing but an equal number began to depolarize. By E18 most cells depolarized. Both hyper- and depolarizations were eliminated by a specific antagonist at kainate receptors (6-cyano-7-nitroquinoxyline-2,3-dione) and by resuspending the cells in Na(+)-free medium. Both responses exhibited a concentration dependency with higher doses evoking stronger effects. In contrast, there was little effect of veratridine in the striatum at E15-E16, and the response to kainate or L-glutamate was predominantly depolarizing during the same embryonic period, with little or no effect until E18. These data show that in the developing CNS, sodium channel responses as well as excitatory aminoacid neurotransmitter responses first become functional in the mesencephalon and subsequently in the striatum, thus suggesting an anatomical gradient of expression. Our results also show that glutamate receptor-coupled functions vary with embryonic age and with regional distribution, suggesting possible roles of glutamate in early CNS embryogenesis, as morphogens or modulators of synaptic plasticity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Distributed changes in rat brain DNA synthesis with long-term habituation and potentiation of the perforant path-granule cell synapse.

The involvement of brain deoxyribonucleic acid (DNA) synthesis in adaptive neural events was studied in the adult rat during long-term habituation (LTH) or potentiation (LTP) of the perforant path-granule cell synapse. Male Long-Evans rats were given 50 muCi [3H]thymidine intraventricularly under urethane anesthesia. Soon thereafter, field excitatory postsynaptic potential (EPSP) slope and population spike were monitored from the right dentate gyrus before and at various times (5, 10, 15, 60 min) following the delivery to the ipsilateral perforant bundle of a low frequency (LFS: 1.0 Hz, 160 s) or a high-frequency train (HFS: 400 Hz, 200 ms), repeated once after 5 min. Unstimulated implanted rats served as controls. DNA synthesis was evaluated by the incorporation of the radioactive precursor into DNA of several brain areas at the end of a 1 h incorporation period. In CA1, LTH and LTP increased DNA synthesis by 30% on the stimulated side. In the entorhinal cortex, LTH but not LTP increased DNA synthesis (by 30%) on the stimulated side. Conversely, in the frontal cortex, LTP but not LTH increased DNA synthesis (by 100%) on both sides. Long-lasting changes in synaptic efficacy covaried non-linearly with DNA synthesis in mono- and polysynaptically stimulated hippocampal regions, and in functionally associated neocortical areas. The co-variations of population spike amplitude were positive for LTH and negative for LTP in the dentate gyrus and frontal cortex of both sides, and in CA3/CA1 of the stimulated side, indicating higher DNA synthesis at lower values of LTH and LTP, and viceversa. Further, regional cross-correlation analyses revealed a high degree of synchronization among brain sites, following low- or high-frequency train pulses, indicating that (i) extra-target sites participate on the stimulated and on the contralateral side, and (ii) small distributed changes take place across the sampled neural networks. A modulatory role of information flow on brain DNA synthesis is inferred to take place in a diffuse, distributed manner.

Animals↗
PubMed1991

EVX2, a human homeobox gene homologous to the even-skipped segmentation gene, is localized at the 5' end of HOX4 locus on chromosome 2.

We isolated and mapped three new human homeoboxes located on chromosome 2 upstream from the reported seven HOX4 homeobox sequences. Two of them, HOX41 and HOX4H, clearly belong to the HOX gene family, in particular to homology groups 1 and 2, and possibly represent the most 5' HOX4 homeoboxes. A third homeobox 13 kb upstream from HOX41 was identified. Sequencing data show that this is the human homolog of the murine Evx-2 homeobox. Both homeoboxes are closely related to the murine Evx-1 and to the frog Xhox-3 homeoboxes. The four genes represent vertebrate homologs of Drosophila even-skipped (eve), a segmentation gene of the pair-rule class. Human EVX2 sequences belong to an active gene because they are transcribed and properly processed in cells and tissues. We have identified for the first time a homeogene of a different class at a HOX locus. These findings are relevant to the understanding of the evolution of HOX gene clusters and their regulation.

Amino Acid Sequence↗