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Biomedical subjects

M Orlando

Publications and source records attributed to M Orlando.

At least 37 records · Page 2Linked to original sources
PubMed2000

New York State universal newborn hearing screening demonstration project: effects of screening protocol on inpatient outcome measures.

OBJECTIVE: To examine differences among various test protocols on the fail rate at hospital discharge for infants in the well-baby nursery (WBN) and neonatal intensive care unit (NICU) who received hearing screening through a universal newborn hearing screening demonstration project. DESIGN: The outcomes of several screening protocols were examined. Two technologies were used: transient evoked otoacoustic emissions (TEOAEs) alone or in combination with the auditory brain stem response (ABR). The performance of test protocols in both nurseries within eight hospitals was examined over a 2- to 3-yr period. In the WBN, six hospitals used a screening protocol of TEOAE technology first followed by an ABR (automated or conventional) technology screening for newborns who referred on TEOAE screening. Two hospitals used TEOAE only in the WBN. Seven hospitals used screening protocols in the NICU that used a combination of TEOAE and ABR technologies (TEOAE technology administered first or second, before or after TEOAE, or TEOAE and ABR tests on all infants). Only one hospital used TEOAE technology exclusively for hearing screening. RESULTS: Significant differences among screening protocols were found across hospitals in the first, second, and third years of the program. The combination of TEOAE technology and ABR technology (a two-technology screening protocol) resulted in a significantly lower fail rate at hospital discharge than the use of a single-technology (TEOAE). Fail rates at discharge were twice as high using the one-technology protocol versus two-technology protocol, even when the best outcomes from program year 3 were considered exclusively. Results of two-technology versus one-technology protocols were similar in the NICU. Use of a second technology for screening TEOAE fails significantly reduced every hospital that used the protocol's fail rate at discharge. CONCLUSIONS: A two-technology screening protocol resulted in significantly lower fail rates at hospital discharge in both the WBN and NICU nurseries than use of a single-technology (TEOAE) hearing screening protocol.

Evoked Potentials, Auditory, Brain Stem↗
PubMed2000

The effect of copayments on drug and alcohol treatment following inpatient detoxification under managed care.

OBJECTIVE: The study examined the rate and duration of outpatient substance abuse treatment following inpatient detoxification under managed care. METHODS: Seven years of claims data from a large behavioral health care carve-out plan were used to identify patients. Rates and duration of formal substance abuse treatment following detoxification were calculated, and regression models were used to explore factors that may affect participation in treatment. RESULTS: Seventy-nine percent of the detoxification patients received formal substance abuse treatment, the majority within the week following discharge. Formal follow-up care lasted an average of ten weeks, with visits occurring on average about once a week. When other variables likely to influence participation in substance abuse treatment were controlled for, the level of outpatient copayments significantly affected the rate of participation in treatment. CONCLUSIONS: These findings indicate that the rate of participation in outpatient treatment after detoxification is high, but room for improvement remains. The results suggest that reducing copayment levels is one mechanism for increasing the likelihood that individuals with severe drug and alcohol problems will receive subsequent treatment. The need for such treatment is underscored by the severity of illness of those who undergo detoxification and the societal costs of untreated substance use disorders.

Adult↗
PubMed2000

Evaluation of techniques for assessing neurobehavioral development in children.

A battery of tests has been designed to explore functional disabilities in children 10-12 years of age arising from adverse conditions during early development. At these ages, it becomes possible to use more complex and challenging tests than those typically used at earlier ages. Although the battery was prompted originally by questions arising from methylmercury exposure, it was also designed for applicability to neurotoxicant exposures arising from pesticides, solvents, persistent organic pollutants such as PCBs and dioxins, other metals, and nutrient excesses and deficiencies as well. The test battery includes the following categories: (1) neuropsychological tests with established psychometric properties not widely exploited in studies of developmental neurotoxicity; (2) electrophysiological and behavioral tests of sensory functioning spanning a broader range of indices than those used generally in studies of neuropsychological development; and (3) adaptations of performance tasks used previously only in animals. The battery was developed in Rochester, New York, and then field-tested on a group of 61 children in the Republic of the Seychelles, where the Ministry of Health had established the Child Development Center. Our findings suggest a number of tests and procedures with the potential for inclusion in test batteries aimed at the exploration of adverse neurodevelopmental effects.

Adolescent↗
PubMed1999

Auditory brainstem response forward-masking recovery functions in older humans with normal hearing.

We investigated the auditory brainstem response (ABR) recovery from forward masking using toneburst maskers and probes. Two subject groups matched for hearing thresholds were evaluated: normal-hearing young adults (21-40 years) and older subjects (63-77 years) with normal audiometric thresholds. Stimuli consisted of 1, 4 and 8 kHz tonebursts, with 2-4 cycle rise/fall time and no plateau. Forward maskers were tonebursts of the same frequency, with a 5 ms rise/fall time and a 20 ms plateau time. Probes were presented at 40 dB above threshold, and the forward masker was adjusted to a level that just eliminated the ABR to the 40 dB sensation level toneburst when the probe onset occurred at masker offset. Forward-masker intervals varied from 2 to 64 ms. ABR wave V latencies were similar for the young and old age groups regardless of toneburst frequency. Under forward-masking conditions, wave V latency was prolonged for the shorter intervals, and recovered to baseline latency by 64 ms. The forward-masker recovery functions were nearly identical for the two age groups for the 1 kHz toneburst. In contrast, there were clear differences in the recovery functions for the two age groups for the 4 and 8 kHz tonebursts. Specifically, the mean latency shift was greater for the aged group for forward-masker intervals of 16 ms or less. The two age groups showed identical latency shifts for longer forward-masker intervals. These data demonstrate prolonged recovery from forward masking in older human subjects. As these subjects had audiometric thresholds within normal limits, one plausible interpretation of this finding is that the prolonged recovery time is a manifestation of an aging effect on the central auditory nervous system rather than the periphery.

Acoustic Stimulation↗
PubMed1999

Single-agent gemcitabine in pretreated patients with non-small-cell lung cancer: results of an Argentinean multicentre phase II trial.

The activity and mild toxicity profile of single-agent gemcitabine therapy in untreated (chemonaive) patients with non-small-cell lung cancer (NSCLC) is well documented. This phase II trial was conducted to determine the objective tumour response rate and toxicity profile of single-agent gemcitabine in pretreated patients with NSCLC. Patients with histological evidence of advanced NCSLC stage IIIB or IV; at least one prior chemotherapy regimen including a platinum or taxane analogue; an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; clinically measurable disease; adequate bone marrow reserve; and adequate renal function; received 1000 mg m(-2) gemcitabine administered over 30 min on days 1, 8 and 15 of a 28-day cycle defined as 3 weekly treatments followed by 1 week of rest. Twenty-nine patients were evaluated for efficacy and 32 for toxicity. One patient achieved a complete response and five patients had a partial response resulting in a total response rate of 20.6% (95% confidence interval (CI) 6-34). Median response duration was 7 months (range 4-11 months). Twelve (41%) patients reached stable disease after two cycles of therapy and 11 (38%) patients had disease progression. Median progression-free survival time was 3 months and median overall survival time was 5.5 months. Toxicity was generally mild (grades 0-2). Severe (grade 3 or 4) haematological toxicities included grade 3 anaemia in one patient and grade 3 thrombocytopenia in two patients. Severe non-haematological toxicities included one patient each with grade 3 liver transaminase elevations, nausea/vomiting and diarrhoea. This study confirms the activity and safety of single-agent gemcitabine in pretreated patients with advanced NSCLC who are refractory or sensitive to first-line therapy.

Antimetabolites, Antineoplastic↗
PubMed1998

DNA fragmentation, DNA-protein crosslinks, postlabeled nucleotidic modifications, and 8-hydroxy-2'-deoxyguanosine in the lung but not in the liver of rats receiving intratracheal instillations of chromium(VI). Chemoprevention by oral N-acetylcysteine.

An in vivo study was carried out with the objectives of evaluating (a) the localization of DNA lesions resulting from exposure to chromium(VI) by the respiratory route, (b) the molecular nature of DNA alterations, and (c) modulation of DNA damage by a known chemopreventive agent. To this purpose, Sprague-Dawley rats received intratracheal instillations of sodium dichromate (0.25 mg/kg body weight) for three consecutive days, and the day after the last treatment lung and liver were removed for DNA purification. The results showed a selective localization of DNA lesions in the lung but not in the liver, which can be ascribed to toxicokinetics and metabolic characteristics of chromium(VI). DNA alterations included DNA-protein crosslinks, DNA fragmentation, nucleotidic modifications, and 8-hydroxy-2'-deoxyguanosine. The last two endpoints were evaluated, for the first time in chromium toxicology, by means of postlabeling procedures. This methodology was adapted to the detection of the DNA damage produced by those reactive oxygen species which result from the intracellular reduction of chromium(VI). The oral administration of the thiol N-acetylcysteine completely prevented any induction of DNA lesions in lung cells.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Effect of satisfaction with one's abilities on positive and negative affect among individuals with recently diagnosed rheumatoid arthritis.

OBJECTIVE: The purpose of this study was to examine the effect that self-evaluation processes have on psychologic well-being among individuals with rheumatoid arthritis (RA). METHODS: The study used a longitudinal research design with 4 data collection points. Participants were 227 adults with recently diagnosed RA. Data were collected via mailed questionnaire and telephone interview. Two dimensions of psychologic well-being were assessed--positive affect and negative affect. RESULTS: We found that, among participants who viewed the abilities being evaluated as very important, greater satisfaction at time 1 was associated with less negative affect at time 2 and time 4. Satisfaction was not associated with positive affect at any of the time points, however. CONCLUSION: Study findings indicate that dissatisfaction with illness-related abilities can exacerbate psychologic distress. The findings also highlight the need for research examining the role that positive affect plays in adaptation to RA.

Activities of Daily Living↗
PubMed1998

In vitro inhibition by N-acetylcysteine of oxidative DNA modifications detected by 32P postlabeling.

Reactive oxygen species are involved in the pathogenesis of cancer and other chronic degenerative diseases through a variety of mechanisms, including DNA damage. We investigated by 32p and 33P postlabeling analyses the nucleotidic modifications induced in vitro by treating calf thymus DNA with H2O2 and CuSO4, interacting in a Fenton type reaction. Six different enrichment procedures and three chromatographic systems were comparatively assayed. The chromatographic system using phosphate/urea, which is more suitable for detecting bulky DNA adducts, was rather insensitive. In contrast, the system using acetic acid/ammonium formate revealed high levels of mononucleotidic modifications. In terms of ratio of adduct levels in treated and untreated DNA, the enrichment procedures ranked as follows: nuclease P1 (19.6), no enrichment (18.3), digestion to trinucleotides (17.6), digestion to monophosphate mononucleotides (8.4), digestion to dinucleotides (3.4), and extraction with butanol (<1.0). The system using formic acid/ammonium formate was quite efficient in detecting 8-hydroxy-2'-deoxyguanosine. Labeling with 33p further enhanced the sensitivity of the method. The oxidative damage was so intense to produce a strong DNA fragmentation detectable by agarose gel electrophoresis, and nucleotidic modifications were more intense when DNA fragmentation was greater. The DNA alterations produced by H2O2 alone were significantly lower than those produced following reaction of H2O2 with CuSO4. The thiol N-acetylcysteine (NAC) was quite efficient in inhibiting both nucleotidic modifications and DNA fragmentation produced in vitro by either H2O2 or the .OH generating system. These results support at a molecular level the findings of previous studies showing the ability of NAC to inhibit the genotoxicity of peroxides and of reactive oxygen species generated by electron transfer reactions.

Acetylcysteine↗
PubMed1996

Human erythrocyte metabolism is modulated by the O2-linked transition of hemoglobin.

The metabolic behaviour of human erythrocytes has been investigated with particular regard to the effect of their oxygenation state. Experiments performed at high phosphate concentration (80 mM) within the pH range 7.0-7.8 on erythrocytes at high (HOS) and low (LOS) oxygen saturation showed that at any pH value: (1) glucose consumption was independent of the oxygenation state; (2) pentose phosphate pathway (PPP) flux was about 2 times higher in the HOS than in the LOS state. At low phosphate concentration (1.0 mM) the PPP flux doubled in HOS as well as in LOS erythrocytes, whereas the decrease in glucose consumption was more marked in the HOS state. Metabolism of LOS erythrocytes approached that of HOS erythrocytes under the following conditions: (1) erythrocytes having band 3 modified by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid; (2) CO-saturated erythrocytes. These data support the hypothesis of a modulation of the relative rates of PPP and glycolysis achieved through competition between deoxy-hemoglobin (deoxy-Hb) and glycolytic enzymes for the cytoplasmic domain of band 3.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1996

Adducts to nuclear DNA and mitochondrial DNA as biomarkers in chemoprevention.

DNA adducts are biomarkers evaluating the biologically effective dose of carcinogens, which reflects, more realistically than the external exposure dose, an enhanced risk of developing cancer. Likewise, inhibition of DNA adduct formation can be assumed as an indicator of decreased risk. Molecular dosimetry techniques can be exploited in anticarcinogenicity studies in animal models as well as in Phase II clinical chemoprevention trials. We have extensively used these end points in animal studies using individual carcinogens and complex mixtures. As assessed by 32P-postlabelling, DNA adducts were formed in the liver of rats fed a diet supplemented with 2-acetylaminofluorene. DNA adducts were detected by synchronous fluorescence spectrophotometry (SFS) in rat liver, lung, heart and testis following intratracheal (l.t) instillations of benzo[a]pyrene. The whole-body exposure of rats to mainstream cigarette smoke resulted in the appearance of DNA adducts in lung, heart, aorta and kidney, whereas adducts were not detected by SFS in liver, brain, oesophagus and testis. Moreover, typical diagonal radioactive zones and multiple DNA adducts were revealed by 32P-postlabelling in the tracheal epithelium, nasal mucosa, aorta and testis of smoke-exposed rats. Formation of adducts to lung DNA, as assessed by both 32P-postlabelling and SFS, also occurred in rats receiving i.t. instillations of air particulate extracts from polluted urban and rural areas. The oral administration of the thiol N-acetylcysteine (NAC) significantly inhibited the formation of DNA adducts in all organs of the rats exposed to the aforementioned carcinogens, which correlated with the parallel inhibition of biochemical, cytogenetic and histopathological alterations as well as with inhibition of preneoplastic and neoplastic lesions in rodents. Our working hypothesis is that DNA adducts in trachea/lung, heart and aorta may be associated with lung cancer, cardiomyopathies and atherosclerosis, respectively. DNA adducts were consistently detectable in the DNA of smooth muscle cells from abdominal aorta specimens taken at surgery from atherosclerotic patients. Even broader are the consequences of mitochondrial (mt) DNA impairment, which has been associated with aging, cancer, and other degenerative diseases. Our data show that adduct levels are consistently higher in mtDNA than in the nuclear DNA in different organs of rats exposed either to benzo[a]pyrene, 2-acetylaminofluorene or cigarette smoke. NAC significantly decreased the formation of adducts to mtDNA when administered with drinking-water. Inhibition of adducts to nuclear DNA is one of the end points evaluated in ongoing Phase II chemoprevention trials in high-risk individuals.

Animals↗
PubMed1991

[Anastomosis or closure of the pancreatic stump after duodenopancreatectomy?].

From 1986 to June 1990, 10 pancreaticoduodenectomies were performed in our Department (VIII Patologia Chirurgica, Università "La Sapienza", Roma). The reconstructive sequence was based on the pancreaticojejunal anastomosis (2 end-to-end pancreaticojejunostomies after invagination, 3 end-to-side Wirsung jejunostomies) in 5 patients. The pancreatic stump was sutured using a 50mm linear stapler in the remaining 5 patients. There was a high incidence (75%) of fistulization after direct suture of the pancreatic stump, although related mortality was null. Among patients treated with pancreaticojejunal anastomosis, a fistula on the end-to-end pancreaticojejunostomy with exitus of the patient, was registered in 1 case. On principle, we believe a end-to-side Wirsung jejunostomy should be performed after pancreaticoduodenectomy. When a safe anastomosis of the pancreatic stump cannot be performed (because of the soft parenchyma, easily lacerable) the technique of the direct suture with stapler is advisable.

Adenocarcinoma↗
PubMed1991

[Reconstructive microsurgery].

Progress in microsurgery has been accomplished by the technical improvements of the operative microscope and other delicate surgical instruments. Therefore, even small arteries as well as female tuba and male deferens, either presenting mechanical obstruction or a section, can be reconstructed. The same procedure may be applied in case of nerve injuries. Since Microsurgery was born, it has been employed in different medical fields offering lately good chances in sterility. Furthermore, microsurgical techniques offer a great support to Plastic Surgery. In fact, it is possible to repair wide tissue damages of the skin, muscles or bones using free flaps. The percentage of success of this Surgery increased the overall percentage obtained in General Surgery. Therefore a close multidisciplinary relation between the different Medical fields is absolutely required for a correct application of microsurgical techniques.

Adolescent↗
PubMed1990

Arrhythmogenic age-related effects of lysophosphatidylcholine in the rat heart.

Ventricular arrhythmias are the most common cause of death among patients with coronary artery disease; this is more evident in the elderly, who tend to have more severe coronary artery disease and age-dependent modifications of cardiac electrophysiology. Lysophosphoglycerides, which accumulate in the ischemic myocardium, are responsible for oscillatory after-potentials and may contribute to the development of ventricular arrhythmias. The aim of this study was to examine the effects of lysophosphatidylcholine (5 x 10(-5) M) in the absence or presence of epinephrine (10(-6) M) in isolated, perfused hearts from adult (6-12 months old) and senescent (24 months old) rats. Rat hearts (30/group) were randomly divided into four groups each of which included hearts of 6, 12 and 24-month old rats. The groups comprised a control group, a group treated with epinephrine, a group treated with lysophosphatidylcholine and a group treated with both epinephrine and lysophosphatidylcholine. Analysis of arrhythmias indicated a linear correlation between epinephrine- and lysophosphatidylcholine-induced ventricular arrhythmias and age. The incidence of arrhythmias was higher in the hearts treated with epinephrine and lysophosphatidylcholine together than in those treated with either substance separately (p less than 0.01). The results indicate that age influences the arrhythmogenic action of lysophosphatidylcholine, and that epinephrine contributes to this effect.

Aging↗
PubMed1990

Synthesis of 1-O-alkyl-2-O-methyl-glycerophospholipids with potential antitumor activity.

Some synthetic alkyl-lysophospholipid analogs have been described as a new class of immunopotentiating and antitumor agents. Among them, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine has been reported to possess the highest antitumor activity. A new method for the synthesis of this compound and of the ethanolamine- and serine-containing analog is reported. 1-Alkyl-2-methyl-rac-glycerol, prepared from 1,2-isopropylidene-glycerol, is phosphorylated and the intermediate is condensed either with N-t-BOC-protected ethanolamine or with N-t-BOC-protected serine benzhydryl ester. The choline-derivative is obtained by methylation with CH3I of the ethanolamine derivative. The same synthetic sequence has been used also for synthesizing compounds unsaturated at the fatty alkyl chain in position 1 of the glycerol moiety. Preliminary observation are reported on the selective cytolytic action of the compounds on a tumor cell line.

Animals↗
PubMed1988

[Action of magnesium salts on the toxic effects of calcium overload in the isolated and perfused rat heart].

The toxic effect of calcium overload and the action of magnesium sulfate (4 mM) and magnesium chloride (4 mM) on heart rate, coronary flow rate, left ventricular systolic pressure, dp/dt max and voltage epicardial electrogram were studied in the isolated and perfused rat heart. Increasing calcium load by increasing [Ca]o from 1 to 6 mM we observed a progressive increase in heart rate coronary flow rate, left ventricular systolic pressure, dp/dt max and a decrease in voltage epicardial electrogram. During the exposure to [Ca]o 8 mM the toxic manifestations of calcium overload developed and we observed a reduction in heart rate, coronary flow rate, left ventricular systolic pressure, dp/dt max and an increase in voltage epicardial electrogram. Magnesium sulfate and magnesium chloride had similar effect: in fact, in both procedures we observed a decrease in heart rate, left ventricular systolic pressure, dp/dt max, voltage epicardial electrogram and an increase in coronary flow rate at [Ca]o 2 mM. When magnesium salts were administered at the same time as the heart was exposed to [Ca]o 8 mM, we observed a reduction in the toxic effect of calcium overload. When magnesium salts were administered after the appearance of the calcium overload, they did not revert the toxic effect of calcium overload but prevented the insurgence of cardiac standstill. Thus, in the isolated perfused rat heart, the toxic manifestations of calcium overload develop at [Ca]o 8 mM and magnesium salts are able to reduce the toxic effects of calcium overload and the appearance of cardiac standstill according to their calcium-antagonism mechanism.

Animals↗
PubMed1987

Factor VII in subjects at risk for thromboembolism: activation or increased synthesis?

In this study the preliminary results obtained by investigating factor VII antigen and activity in 38 subjects with arterial disease of the extremities are reported. The antigen determination (VII:Ag) was performed by using an inhibitor neutralization assay; factor VII activity (VII:C) was determined by one-stage assay with human factor VII artificially depleted plasma. All the patients showed increased levels of VII:C and VII:Ag compared to the reference population (p less than 0.001). There is a significant correlation between VII:C and VII:Ag (r = 0.47), but the ratio VII:C/VII:Ag is slightly increased. Our results confirm that elevated levels of factor VII are present in patients with tendency to thrombosis.

Adult↗
PubMed1985

Carrier detection in factor VII congenital deficiency.

Thirty obligate and 28 possible carriers of factor VII congenital deficiency, belonging to 16 families, were studied in relation to the immunological variants to which the kindreds belonged, namely, VII+, VIIR and VII-. Factor VII activity and antigen determinations in these subjects formed two phenotypical patterns: a discrepant pattern characterized by a low ratio activity/antigen present in VII+ heterozygotes, and a non-discrepant pattern (normal ratio activity/antigen) which is present in the VII- and VIIR variants. In the first genetic variant the detection of carriers can be performed using the ratio VII:C/VII:Ag. In the other variant, which accounts for the vast majority of heterozygotes, the distribution of the carriers' factor VII is so widespread that a large overlap results between these subjects and the normals. The application of a probabilistic calculation performed by combining the actual values of factor VII:C and the genetic probability of carriership using Fisher's linear discriminant analysis, makes discrimination between carriers and normals easier.

Adolescent↗