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Biomedical subjects

F De Marco

Publications and source records attributed to F De Marco.

At least 19 recordsLinked to original sources

Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial.

This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged <or=60 were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. Main findings are as follows: (1) 5.5-years overall survival projection of 80% (median follow-up: 68 months), with no differences related to age-adjusted IPI score; (2) 46 (50%) of 92 patients presently in continuous complete remission; (3) projected long-term progression-free survival exceeding 80% for patients collecting PCR-negative stem cell harvests or achieving molecular remission within the first 2 years from the end of therapy; (4) actuarial 5-years risk of developing secondary myelodysplasia and acute myeloid leukemia of 3.7%, with most of these events occurring in patients re-treated for recurrent lymphoma. These results demonstrate that i-HDS is feasible, effective and safe even in terms of long-term outcome. As the HDS schedule can be easily supplemented with Rituximab, it is one of the best options for random comparison with Rituximab-supplemented conventional chemotherapy.

Adolescent↗

Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly spaced high-dose chemotherapy courses with G-CSF.

The purpose of the study was to compare telomere length (TL) in peripheral blood progenitor cells (PBPC) collected after two tightly spaced high-dose (hd) chemotherapy courses. We assessed 37 previously untreated lymphoma patients undergoing a hd-chemotherapy program with autografting. They sequentially received hd-cyclophosphamide (CY) and hd-Ara-C, both followed by PBPC harvesting. Both post-CY and post-Ara-C harvests were assessed for TL by Southern blot analysis. In 12 patients, the assay was also performed on purified CD34+ cells. All patients displayed high PBPC mobilization following both hd-CY and hd-Ara-C. In all but one patient, TL was shorter in PBPC collected after Ara-C compared to CY: 7226bp (range: 4135-9852) vs 8282 bp (range 4895-14860) (P < 0.0001). This result was confirmed on CD34+ cells. Platelet recovery in patients receiving post-Ara-C PBPC was significantly slower compared to those receiving post-CY PBPC. In conclusion, (i) administration of tightly spaced hd-chemotherapy courses induces marked telomere shortening on harvested PBPC; (ii) engraftment kinetics seem slower, with delayed platelet recovery, in patients autografted with PBPC suffering marked TL erosion; (iii) long-term follow-up is required to verify whether PBPC with shortened telomeres display defective engraftment stability and/or risk of secondary leukemia; (iv) TL evaluation is advisable whenever new mobilization procedures are developed.

Adolescent↗

Detection of HPV in genital condylomata: correlation between viral load and clinical outcome.

High DNA viral load in Human Papillomavirus type 16 cervical dysplastic lesions has been proposed as a marker of progression towards malignancy. To evaluate the prognostic value of DNA viral load in infection by HPV type other than HPV-16, a longitudinal study of patients with Anogenital Condylomata (AC) was designed. The study included 40 patients, 25 men and 15 women. Clinical data were collected through standard interview and routine serum analyses. Viral type in lesions was assayed by PCR with general primers (MY09-MY11) and Restriction Fragment Length Polymorphism (RFLP). Viral load was determined by PCR end point determination with type specific primers on serial sample dilutions. The duration of ano-genital lesions upon liquid nitrogen standard cryotherapy or Podofillin chemotherapy was correlated with viral and clinical data. Patients with higher lesional viral load at study entry showed a markedly longer disease clinical course than patients with lower viral loads. The HPV-6 was observed in 31 out of 40 patients (77.5%), much more frequently than HPV-11 (7/40 17.5%), the latter being associated with higher titres of viral load. Two cases (5%) remained undetermined. No HPV-16 or other high-risk type was detected, while HPV-61, not uncommon in Italy, was found once in a double infection carried by an HIV positive patient. No significant association was observed between clinical outcome and demographic and epidemiological data, or risk factors.

Anus Diseases↗

Physical state and expression of human papillomavirus in laryngeal carcinoma and surrounding normal mucosa.

Epidemiologic and biomolecular evidence suggests that human papillomavirus (HPV) infection may be associated with the development of head and neck cancers. To clarify the role of HPV in larynx carcinoma, 25 patients were studied for the presence of viral DNA, possible virus integration into the cellular genome, and viral expression both in neoplastic tissues and in neighbouring normal mucosa. Twelve of 25 patients with neoplasia (48%) showed negative results for HPV sequences, and 13 (52%) showed positive results. Among the latter group of patients, seven were HPV-16 positive, five were HPV-6, and one was HPV-45. No multiple infections were detected. The physical status of the HPV genome was analysed by three methods: polymerase chain reaction (PCR), bidimensional agarose gel electrophoresis, and in situ hybridisation. Viral integration into the host genome occurred in 43% of cases of HPV-16 and in 20% of cases of HPV-6. Viral RNA expression was detected by reverse transcription-PCR only in HPV-16-positive tumours. The pattern of expression was consistent with an active role of HPV in cellular transformation. In conclusion, the present work suggests that HPV infection may be involved in some cases of laryngeal carcinoma. However, the transformation mechanisms might be different from those currently accepted for anogenital cancers.

Adult↗

Induction of apoptotic cell death by IFNbeta on HPV-16 transformed human keratinocytes.

Apoptosis, or 'programmed cell death' is a process of general biological relevance with implications in several physiological and pathological conditions of the skin. However, little is known about its induction in keratinocytes by regulator agents. In this work we demonstrate that IFNbeta, but not IFNalpha, selectively induces programmed cell death in HPK-Ia cells, a line derived from human keratinocytes transformed with HPV-16 DNA. This IFNbeta-triggered apoptosis is strictly dependent on a serum-induced partially differentiated phenotype; it occurs through the activation of a check point in the early 'S' phase, where the cells are arrested and eventually driven to apoptosis. These data indicate that apoptosis may be induced in keratinocytes by a regulator agent combined with a differentiating stimulus.

Antiviral Agents↗

Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study.

AIM: To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria. METHODS: Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored. RESULTS: The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0%, vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups. but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators' global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01). CONCLUSIONS: Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does.

Colonic Diseases, Functional↗

Clinical trials among worker populations: the value and significance of anamnestic findings and clinical and instrumental tests for diagnosing work-related musculoskeletal disorders of the upper limbs (WMSDs).

The authors discuss the value and significance of symptoms in WMSDs, in view of the fact that the anamnestic threshold proposed in epidemiological investigations cannot be used as clinical and diagnosing criteria. Some useful clinical procedures are suggested for cases where there is a suspicion of musculoskeletal disorders of the cervical spine and upper limbs, bearing in mind that they are to be applied within the framework of health surveillance programmes undertaken by health care practitioners who are not specialists in orthopaedics, physiatrics or neurology. The recommendations for instrumental tests and specialist referrals are also discussed for the various disorders. The authors also provide flow charts for the diagnostic procedures pertaining to WMSDs. The appendix shows a sample patient chart illustrating the proposed procedures; it also permits the findings to be encoded so that they can be stored in a dedicated database. The codes for diagnosing WMSDs are also reported for the same epidemiological purposes.

Brachial Plexus Neuritis↗

Criteria for the health surveillance of workers exposed to repetitive movements.

In the light of the experience and guidelines developed by other countries and of Italian legislative and operational conditions, the authors outline a strategy for a health surveillance programme for work-related musculoskeletal disorders of the upper limbs. In particular, the paper defines the various aims of the health surveillance programme and identifies significant relevant criteria for its implementation (i.e. existence of risks or effects). A screening schedule is presented based on subsequent investigations (first and second level surveillance); the authors discuss the principal methods used for processing the results of the health surveillance programme, in collective (i.e. statistical comparisons, planning of periodical investigations) and individual terms (job fitness judgements, reporting of suspected occupational diseases).

Humans↗

Effects of fasting and refeeding on energetic metabolism of cold acclimated rats.

In rats acclimated at 5 degrees C or 28 degrees C (thermal neutrality), overnight fasting induced decreases in body and brown adipose tissue (BAT) weights and led to a larger decrease in resting metabolism (RM) in the 5 degrees C rats than in the 28 degrees C group. Refeeding significantly enhanced RM (diet-induced thermogenesis) in a greater extent in 5 degrees C than in 28 degrees C rats. This effect was inhibited by propranolol (beta adrenergic receptor antagonist) in 28 degrees C but was only halved in 5 degrees C rats. The capacity for nonshivering thermogenesis as determined by norepinephrine infusion was reduced by fasting only in 28 degrees C group; it remained unchanged in cold acclimated rats despite the large lipid utilization induced by fasting.

Acclimatization↗

Effects of partial sympathectomy of brown fat or of adrenomedullectomy on catecholamine metabolism in cold-reared rats.

1) The aim of this work was to study the effects of surgical denervation of the interscapular brown adipose tissue (IBAT) and of bilateral adrenal demedullation on cold adaptation of rats. 2) After sympathectomy in the 28 degree C rats, there were substantial decreases in the IBAT NE basal level and turnover rate but no modifications in the heart and adrenals. In the 16 degree C rats there were also decreases in the basal level and turnover rate of the IBAT NE but, in addition, significant increases in levels and turnover rates of NE in the heart and of epinephrine in the adrenals. 3) Bilateral adrenal demedullation led to increases in the NE basal level and turnover rate in the IBAT and the heart in the 16 degree C rats; no effects were observed in the 28 degree C rats. 4) It is concluded that in rats born and reared in a mild cold environment a compensatory stimulation of catecholamine production and turnover rate occurs in some organs after a partial sympathectomy of BAT or bilateral adrenal demedullation.

Adipose Tissue, Brown↗

Metabolic changes associated with sustained 48-hr shivering thermogenesis in the newborn pig.

Metabolic changes associated with sustained 48-hr shivering thermogenesis were studied in piglets maintained at 34 (thermoneutrality) or 25 degrees C (cold) between 6 and 54 hr of life. Despite their high shivering activity and elevated heat production, cold-exposed piglets exhibited a slightly lower rectal temperature than thermoneutral animals (-1.1 degrees C; P < 0.01) at the end of the treatment. The enhancement of heat production and shivering activity were associated with a decrease in muscle glycogen (-47%; P < 0.05) and total lipid content (-23%; P < 0.05), a reduction of blood lactate levels (P < 0.05) and an enhancement of muscle cytochrome oxidase activity (+20%; P < 0.05) which suggests that muscle oxidative potential was increased by cold exposure. Potential for capturing lipids (lipoprotein lipase activity) was also higher in the red rhomboideus muscle (+71%; P < 0.01) and lower in adipose tissue (-58%; P < 0.01) of the cold-exposed piglets. Measurements performed at the mitochondrial level show no changes in rhomboideus muscle, but respiratory capacities (state IV and FCCP-stimulated respiration) and intermyofibrillar mitochondria oxidative and phosphorylative (creatine kinase activity) capacities were enhanced in longissimus dorsi muscle (P < 0.05). These changes may contribute to provide muscles with nonlimiting amount of readily oxidable substrates and ATP necessary for shivering thermogenesis. A rise in plasma norepinephrine levels was also observed during the second day of cold exposure (P < 0.05).

Animals↗

Effects of the level of asphyxia during delivery on viability at birth and early postnatal vitality of newborn pigs.

Newborn pigs (n = 117) were used to provide information on the relationships of degree of asphyxia during delivery, viability at birth, and some striking aspects of postnatal vitality including survival, interval between birth and first udder contact and between birth and first suckling, rectal temperature at 24 h of life (RT24), and growth rate over the first 10 d of life. The degree of asphyxia at birth was estimated from cord blood pCO2, pH, and lactate levels. Onset of respiration, heart rate, skin color, and attempts to stand during the first minute after birth were used to estimate the viability score. Neonatal asphyxia, i.e., decreased blood pH and increased blood pCO2 and lactate, was associated with the production of unusually high levels of catecholamines. The degree of asphyxia increased with late position in the birth order (P < .01) and was higher in piglets born posteriorly (P < 0.5). Further, the average blood pCO2 within a litter increased (P < .05) with litter size. The was an inverse relationship between the degree of asphyxia and the viability score (P < .001). Highly viable piglets reached the udder more rapidly (P < .001) and had a higher RT24 (P < .001) than those of low viability. Plasma glucose concentrations increased with blood pCO2 and plasma epinephrine concentrations (P < .001). Neonatal asphyxia reduced postnatal vitality by delaying the first contact with the udder (P < .03) and was associated with a lower RT24 (P < .05), growth rate (P < .001), and survival over 10 d (P < 0.06). These variables, i.e., interval between birth and first udder contact, RT24, and growth rate, were correlated with birth weight (P < .001); RT24 was also shown to decrease (P < .001) with the time taken to reach the udder. Overall, results suggest that piglet suffering from asphyxia during delivery are less viable at birth and less prone to adapt to extrauterine life.

Animals↗

Interferon-beta strong cytopathic effect on human papillomavirus type 16-immortalized HPK-IA cell line, unexpectedly not shared by interferon-alpha.

We report a novel, unusually severe cytopathic effect of interferon-beta (IFN-beta). Data concerning antibody neutralization, induction and recovery time course, CPE50 dose, impact on oxidative metabolic activity and 1D SDS-PAGE total cellular protein analysis are provided for preliminary characterization. This cytopathic effect appears to be linked to human papillomavirus type 16 (HPV-16) genome presence as it is markedly evident in the HPV-16-immortalized HPK-IA cell line, but is not induced in diploid keratinocytes. It is also not induced in highly malignant SiHa cells suggesting that it also requires a fairly conserved phenotype. This effect is unexpectedly not shared by IFN-alpha pointing to a discrimination between IFN-alpha and -beta signal despite the well-known sharing of a common receptor. It remains to be clarified whether this divergence, undetectable in other cellular systems, represents a direct effect of viral presence or a non-specific consequence of cellular homoeostatic disregulation induced by the papillomavirus genome.

Cell Line, Transformed↗

Cold-induced changes in circulating levels of catecholamines and thyroid hormones are modulated by energy intake in newborn pigs.

Newborn pigs were kept at a low ambient temperature from 6 until 54 h of age and supplied with a limited (LI, 415 g (kg body weight)-1) or a high (HI, 655 g (kg body weight)-1) intake of milk. At the end of the treatment, both groups had similar deep body temperatures and metabolic rates. However, plasma adrenaline and noradrenaline levels were, respectively, 5.8- and 3.0-fold lower (P < 0.01) in HI than LI piglets, whereas plasma 3,5,3'-triiodothyronine (T3) was 1.5-fold higher (P < 0.01) in HI piglets. It is concluded that the hormonal control of cold-induced thermogenesis is modulated by energy intake, with catecholamines and thyroid hormones acting in a closely related and complementary manner.

Aging↗

Serotonin level and turnover rate in brown adipose tissue of developing rats.

The level and turnover rate (TR) of serotonin (5-HT) were determined in the brown adipose tissue (BAT) of rats born and reared at 28 degrees C and 16 degrees C. The serotonin/norepinephrine ratio was high in BAT of both groups for the first 2 days. Thereafter it fell. During the first 3 days, the TR was three times higher in 16 degrees C rats than in 28 degrees C rats. A similar difference was observed for the 5-HIAA/5-HT ratio during that period. It is concluded that 5-HT may act on BAT thermogenesis in cold-exposed pups but its mechanism of action is still hypothetical.

Adipose Tissue, Brown↗

Chlamydia trachomatis genitourinary infections: laboratory diagnosis and therapeutic aspects. Evaluation of in vitro and in vivo effectiveness of azithromycin.

Chlamydia trachomatis (C.t.) cell culture represents a sensitive method for the diagnosis of chlamydial infection and the only one which makes it possible to determine the susceptibility of an isolate to antibiotics so that an appropriate drug can be selected for individual treatment. In 11 patients, affected by urethroprostatitis and suspected of treatment failure with standard drug regimens, either due to lack of compliance with therapy or antibiotic resistance, C.t. was isolated in McCoy cell culture from urethral swabs, after prostatic massage. The in vitro activity of azithromycin against these isolates and the in vivo efficacy of the drug in the patients treated with a single 1 g dose have been evaluated. All the C.t. strains tested were susceptible to the action of azithromycin (MIC range 0.125-1.0 microgram/ml). Bactericidal values were one dilution higher (MBC range 0.25-2.0 microgram/ml). These in vitro results are consistent with clinical observations as all the patients treated had negative culture at a 4-week follow-up visit.

Azithromycin↗

Postnatal development of nonshivering thermogenesis in rats: effects of rearing temperature.

A comparative chronological study (from 1 to 33 days post partum) was performed to establish the capacity for nonshivering thermogenesis (NST) in rats born and reared at 28 degrees C and at 16 degrees C. The resting metabolism measured at 33 degrees C was higher in the 16 degrees C rats than in the 28 degrees C rats from the 3rd day. When expressed per weight or per surface area units it was higher in 16 degrees C pups than in 28 degrees C pups until the end of the 3rd week. In fact the resting metabolism was significantly proportional to different powers of weight (W0.67 at 16 degrees C and W0.75 at 28 degrees C) during the suckling period. At birth, respiratory quotient (RQ) was the same in both groups (0.70); it increased slowly to the end of the 3rd week (about 0.80). During the 3rd week RQ was lower in 16 degrees C rats than in 28 degrees C animals. This indicates that 16 degrees C rats are more dependent on the milk supplied by their mother. After weaning there were no differences in RQ values (0.90). Rectal temperature was low in both groups on day 1 (about 32 degrees C). It increased until weaning when it stabilized at 37 degrees C. From day 1 to day 18, it was significantly lower in cold reared rats. The capacity for NST was measured by investigating the effect of an injection of norepinephrine (NE) on the metabolic rate at 33 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗