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Biomedical subjects

F Lombardi

Publications and source records attributed to F Lombardi.

At least 109 records · Page 6Linked to original sources
PubMed1993

Biliary excretion of rufloxacin in humans.

Rufloxacin is a new once-daily antibacterial fluoroquinolone with a long half-life. The aim of the present study was to evaluate the plasma and biliary kinetics and biliary and urinary excretion of rufloxacin in patients with extrahepatic cholestasis. Twelve patients with total external percutaneous transhepatic biliary drainage were given a single oral dose of 400 mg of rufloxacin. Plasma, bile, and urine samples and fractions were collected over 72 h after drug administration. Rufloxacin and its major metabolite, the N-desmethyl derivative, were measured by high-performance liquid chromatography. Maximum rufloxacin concentrations in plasma and bile (means +/- standard deviations) were 4.05 +/- 1.38 micrograms/ml and 8.24 +/- 7.16 micrograms/ml, respectively, and were reached in 4.2 +/- 3.0 h and 4.2 +/- 3.5 h, respectively. The terminal elimination half-life of rufloxacin in plasma was 45.1 +/- 13.5 h. Apparent plasma clearance was 31.3 +/- 10.5 ml/min, while biliary clearance was 0.4 +/- 0.2 ml/min and renal clearance was 12.7 +/- 6.0 ml/min. In 72 h, 0.9% +/- 0.8% of the dose given was recovered in bile and 27.2% +/- 12.0% was recovered in urine. Biliary concentrations exceeded the MICs of most common biliary tract pathogens for at least 24 h after administration. The broad antibacterial spectrum of rufloxacin and its high and prolonged biliary concentrations suggest that this drug may be useful for treatment of biliary tract infections.

Administration, Oral↗
PubMed1993

Effect of captopril on sympathetic preganglionic efferent activity in cats.

In 13 decerebrate cats, we studied the effects of captopril (10 mg/kg iv bolus) on the background discharge of thoracic preganglionic sympathetic fibers. After drug administration there was an initial reduction in systolic arterial pressure (SAP), which was followed by a later inhibition of sympathetic discharge (from 2.7 +/- 0.5 to 0.79 +/- 0.1 imp/0.1 s; P < 0.01). Captopril significantly reduced the excitatory response of sympathetic fibers to premature ventricular contraction (70 +/- 17 vs. 257 +/- 30%), inferior vena cava obstruction (176 +/- 56 vs. 315 +/- 85%) and asphyxia (143 +/- 20 vs. 245 +/- 51%). Vice versa the sympathetic response to aortic occlusion was unaffected (-58 +/- 8 vs. -62 +/- 6%). A similar reduction in sympathetic discharge was observed after captopril administration in anesthetized cats (n = 3). On the contrary, no changes in background neural discharge were noticed in decerebrate-spinalized cats (n = 5), despite comparable hemodynamic effects. These data indicate that captopril reduces sympathetic efferent activity and its responsiveness to excitatory stimuli. The lack of neural effects in decerebrate-spinalized cats is consistent with a brain stem site of action of captopril.

Animals↗
PubMed1993

Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas.

PURPOSE: A single-center, prospective, nonrandomized trial was conducted to evaluate therapeutic results of a short-term program of chemotherapy followed by locoregional radiotherapy in stage I or II intermediate/aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1985 to 1990, 183 consecutive patients with a diagnosis of NHL (Working Formulation [WF] E through J excluding Burkitt's type), Ann Arbor stage I or II, and no more than three sites of disease involvement were treated with four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (six cycles in partial responders). Radiation therapy to initial sites of disease involvement (40 to 44 Gy) and to proximal uninvolved nodal region (36 Gy) was delivered shortly after completion of the chemotherapy program. RESULTS: The complete remission (CR) rate was 98% at the end of combined therapy. Diagnostic excision of all measurable disease was performed in 33% of patients. In the remaining patients, 87% achieved CR with chemotherapy and 11% with radiation therapy, while three patients failed to achieve CR. After a median follow-up of 51 months, 26 patients have relapsed and 25 have died. The 5-year relapse-free and total survival rates were 83%. Aside from age older than 60 years, no other factor such as histology, stage, extranodal disease, bulky lymphoma, or abnormal lactic dehydrogenase (LDH) could predict for treatment outcome. There was a trend toward higher relapse rate for patients achieving CR at the time of radiation therapy (31%) as opposed to patients achieving CR with chemotherapy (15%) or with initial surgery (10%). Treatment was well tolerated and no deaths due to acute toxicity were observed. CONCLUSION: For patients who present with limited-stage, aggressive NHL, a short course of CHOP chemotherapy followed by locoregional irradiation is safe, highly effective, and curative for most. Therefore, at the present time this approach can be regarded as standard therapy for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Hypotension following maximum physical exercise. Evaluation of hemodynamic and humoral mechanisms].

The period after exercise has received little attention although there are rapid and arge changes in the loading conditions of the heart and circulation which may precipitate hypotension or arrhythmias. Little is known of the time course of the recovery of cardiac output and humoral changes occurring during this periods. After a single bout of prolonged muscular exercise, systolic and diastolic blood pressure decrease, sometimes for several hours. In a recent controlled study for the possible effects of the expecting of the exercise, a reduction in diastolic blood pressure was observed particularly in the first 10 min and lasting to 60 min. The mechanisms of the acute hypotensive effect of upright dynamic exercise have not yet been clarified. Little is known of the time course of the recovery of cardiac output, humoral and autonomic changes occurring during this period. Conflicting data are presented by different authors. The aim of the present study was to study the role of the haemodynamic and humoral changes in the modifications in blood pressure occurring in the hour of recovery after maximal exercise in normal subjects. Nine normal male volunteers (age: 28:34 years) have been studied on 2 separate days. Subjects were studied on a non-exercise (control) day (the subjects maintained the upright position for 30 min, followed by 60 min supine) and an exercise day (maximal upright bicycle exercise followed by supine rest for 60 min), in a random order. The following data have been recorded before the test and serially during 60 minute supine: systolic and diastolic blood pressure, heart rate, haemodynamic changes (by suprasternal aortic Doppler), and humoral changes (renin).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Beta-blocking effect of propafenone based on spectral analysis of heart rate variability.

RR variability was analyzed in 15 patients with ventricular arrhythmias to evaluate whether the antiarrhythmic action of propafenone is associated with alteration of neural control mechanisms. Before drug administration, spectral analysis of RR variability was characterized by 2 major components at low and high frequency, which are considered to reflect sympathetic and parasympathetic modulation of the heart period. After propafenone (600 to 900 mg/day), there was a marked reduction in RR variance (826 +/- 184 to 412 +/- 77 ms2; p < 0.05), although the mean RR interval was unchanged. The drug significantly reduced the low-frequency component (52 +/- 6 to 28 +/- 4 nu) and augmented the high-frequency component (39 +/- 6 to 55 +/- 5 nu). As a result, the low-/high-frequency ratio (an index of sympathovagal balance) decreased from 2.0 +/- 0.4 to 0.6 +/- 0.1. A positive correlation between serum levels and drug-induced changes in the low-frequency component was also observed. Furthermore, the increase in the low-frequency component induced by tilt (53 +/- 5 to 79 +/- 3 nu) was markedly attenuated after drug administration (27 +/- 5 to 54 +/- 7 nu). Thus, propafenone administration is associated with changes in spectral components that are consistent with a beta-blocking effect of the drug.

Adrenergic beta-Antagonists↗
PubMed1992

High-performance liquid chromatographic determination of rufloxacin and its main active metabolite in biological fluids.

A high-performance liquid chromatographic method is described for the determination of a fluoroquinolone, rufloxacin, and its N-desmethyl metabolite in plasma, urine and bile. Samples are chromatographed on a poly(styrene-divinylbenzene) column, the eluate being monitored with a fluorescence detector. The method was validated and a detection limit of 10 ng/ml for both rufloxacin and its metabolite in all the biological matrices considered was found. The method was successfully applied in pharmacokinetic studies.

Anti-Infective Agents↗
PubMed1992

Circadian variation of spectral indices of heart rate variability after myocardial infarction.

The circadian variations of spectral indices of heart rate variability were analyzed in 20 patients 4 weeks after a first and uncomplicated myocardial infarction (MI) and in 20 control subjects. R-R interval and variance showed a characteristic day-night pattern with a significant reduction of the latter parameter in patients after MI (10,967 +/- 1109 msec2 vs 16,860 +/- 2132 msec2). Control subjects were characterized by a predominance of low-frequency (approximately 0.1 Hz) component during the day and of high-frequency (approximately 0.25 Hz) component during the night, which reflected the expected 24-hour pattern of variation of sympatho-vagal balance. A 24-hour elevation (64 +/- 3 normalized units [nu] vs 56 +/- 2 nu; p less than 0.05) of the low-frequency component and a smaller (23 +/- 2 nu vs 32 +/- 2 nu; p less than 0.05) high-frequency component during the night differentiated patients after MI from subjects. The difference between the two groups was even more evident when the 24-hour sympatho-vagal balance was assessed with the low frequency/high frequency ratio. Thus spectral analysis of heart rate variability indicates that in patients after MI there is an alteration of neural control mechanisms as indicated by the presence of signs of sympathetic activation and by the attenuation of the nocturnal increase in vagal tone.

Aged↗
PubMed1992

Spectral analysis of sympathetic discharge, R-R interval and systolic arterial pressure in decerebrate cats.

In 19 decerebrate and artificially ventilated cats, we analyzed, with a power spectral methodology, the variability simultaneously present in R-R interval and in thoracic preganglionic sympathetic outflow. R-R interval was characterized, as already described in humans and other experimental preparations, by two rhythmic components occurring at a frequency of about 0.1 Hz (low-frequency, LF) and at one corresponding to respiratory rate (high-frequency, HF) which, in these experiments, was set at 0.32 Hz. Two similar rhythmic components were also present in the sympathetic discharge. Arterial pressure changes were produced by aorta or vena cava flow obstruction in order to produce reflex responses in sympathetic activity. Reflex sympathetic excitations induced an increase in the LF component of both R-R interval and sympathetic discharge variabilities, while the HF components were simultaneously reduced. In contrast, reflex sympathetic inhibitions were accompanied by a decrease in LF components of both variability signals, while the HF components were simultaneously increased. A significant and positive correlation was found between changes in impulse activity and the amplitude of LF component of either R-R interval or sympathetic discharge variabilities. These data support the hypothesis that the low-frequency component of R-R variability can be used as a marker of sympathetic modulation.

Animals↗
PubMed1992

Hypofractionated accelerated radiotherapy in osteogenic sarcoma.

A method of hypofractionated accelerated radiotherapy (3 weekly fractions of 6 Gy over 2 weeks to a total tumor dose of 36 Gy) was used as single modality in 14 patients with osteogenic sarcoma for palliative treatment of the primary tumor site (six cases) or skeletal metastases (15 sites). A durable response, radiologically assessed, was obtained in 17 of the 21 (81%) irradiated sites. When this irradiation modality was combined with chemotherapy, to treat patients presenting with synchronous metastases (eight cases) or refusing amputation (five cases), a radiologically assessed response was observed in 12 of 13 (92%). In no case did a local recurrence occur before surgery or death because of progressive disease elsewhere. Of the seven patients who later had to undergo ablative surgery, a 100% and 95% tumor necrosis was observed in 6 and 1, respectively. Because of intralesional resection of primary osteogenic sarcoma after preoperative chemotherapy, seven additional patients were irradiated. None recurred at the level of the primary site. Although effective in inducing remission of osteogenic sarcoma, this irradiation method produced severe damages to normal tissues in a high proportion of patients.

Adolescent↗
PubMed1992

Effects of mexiletine, propafenone and flecainide on signal-averaged electrocardiogram.

The effects of mexiletine, propafenone and flecainide on the parameters of signal-averaged electrocardiogram in 40 subjects with symptomatic and repetitive ventricular arrhythmias were studied. Mexiletine (n = 16) suppressed ventricular arrhythmias in 10 patients and did not produce any significant changes in filtered QRS duration (fQRS), root mean square voltage of the final 40 ms of filtered QRS (RMS40) or low amplitude terminal component duration (LAS40). Acute (n = 8, 450 mg) and chronic (n = 16, 600-1200 mg.day-1) administration of propafenone determined a significant increase in fQRS (from 123 +/- 2.2 to 139 +/- 3 ms) and a reduction in RMS40 (from 54 +/- 8.8 to 34 +/- 6.7 microV); as a consequence the incidence of ventricular late potentials rose from 43 to 62%. The observed effects were independent of anti-arrhythmic efficacy, which was 86% for this drug. Acute (n = 8, 200 mg) and chronic (n = 13, 200-300 mg.day-1) administration of flecainide was associated with a marked prolongation in fQRS (from 123 +/- 2.8 to 138 +/- 4.1 ms) and a reduction in RMS40 (from 69 +/- 11.5 to 47 +/- 11 microV); thus determining an increase in the incidence of ventricular late potentials from 29 to 48%. Changes in signal-averaged electrocardiogram were not related to drug efficacy, which was 81%. These data indicate that 1c anti-arrhythmic drugs consistently modified the parameters of signal-averaged electrocardiogram; the observed changes might reflect an inhomogeneous slowing of intramyocardial impulse propagation.

Adult↗
PubMed1992

Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor infusion makes high-dose etoposide a safe outpatient regimen that is effective in lymphoma and myeloma patients.

PURPOSE: This study assessed the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or recombinant human granulocyte colony-stimulating factor (rhG-CSF) in ameliorating the extent and duration of hematologic toxicity after high-dose etoposide cancer therapy. PATIENTS AND METHODS: Thirty-two non-Hodgkin's lymphoma and myeloma patients were treated with 2 to 2.4 g/m2 etoposide infused intravenously (IV) during a 10- to 12-hour period, followed 72 hours later by subcutaneous administration of rhGM-CSF or rhG-CSF. Hematologic toxicity was compared with that observed in 29 patients who were treated with high-dose etoposide without growth factors. RESULTS: The median duration of grade 4 neutropenia in growth factor-treated patients was 3 days, and granulocyte counts never decreased to less than 100/microL in approximately half of the patients. The corresponding figures in the control patients were 8 and 3 days, respectively (P < .0001). No effect was observed in platelet and RBC recovery. Growth factor-treated patients became eligible to receive additional myelotoxic chemotherapy a median of 5 days earlier than controls. Nonhematologic toxicity was minimal. Grade 1 mucositis was observed in two of 61 patients (3%). Antitumor activity assessed within 1 month after etoposide administration was documented in 58% of 38 assessable patients. Finally, high-dose etoposide expanded and mobilized the pool of peripheral-blood hematopoietic progenitors. CONCLUSION: The use of rhGM-CSF or rhG-CSF makes high-dose etoposide a safe outpatient regimen and should encourage the inclusion of this highly effective and well-tolerated drug in novel treatment strategies that use high-dose therapy early in the clinical course of chemosensitive tumors.

Adult↗
PubMed1992

Autonomic nervous system adaptations to short-term exercise training.

Signs of sympathetic hyperactivity and low parasympathetic activity have been found during the acute and recovery phases of myocardial infarction and have been associated with an increased risk of cardiac mortality. Beneficial effects of physical training have been recently reported in post-myocardial infarction patients. We tested the hypothesis that physical training would be effective in improving the autonomic balance by studying 22 patients with a first and recent myocardial infarction who were randomly assigned to enter or not enter a 4-week in-hospital physical training program. Spectral indices of heart rate variability were analyzed at rest and during 70 degrees head-up tilt before and after the index training, not training period. As expected, physical training induced a significant increase in exercise duration (13.7 +/- 0.8 vs 17.1 +/- 0.1 min, p less than 0.001) and in the anaerobic threshold (9.5 +/- 0.7 vs 12.0 +/- 1.0 min, p less than 0.02) in trained patients, while no changes were observed in the untrained group. At entry, in both groups, spectral profile of heart rate variability was characterized by a predominant LF component and a smaller HF component with no further modification after head-up tilt. After 4 weeks, in resting conditions, no significant changes in spectral components were observed in both trained and untrained patients. After physical training, head-up tilt produced significant modifications in spectral profile with an increase in the LF component (84 +/- 3 vs 69 +/- 5 nu, p less than 0.01) and a decrease in the HF component (7 +/- 1 vs 19 +/- 4 nu, p less than 0.05) in trained patients, while no changes were observed in the untrained patients. Our data suggest that in postmyocardial infarction patients, 4 weeks of physical training may induce an improvement in the autonomic balance with a restoration toward normal in the reflex activity of the system.

Adaptation, Physiological↗
PubMed1992

Power spectral analysis of RR variability.

The analysis of beat-to-beat spontaneous oscillations of heart rate variability is a recent and noninvasive approach capable of providing important information on neural mechanisms controlling cardiovascular function. In particular, with spectral analysis of RR variability, two major components can be detected at low (LF, approximately 0.1 Hz) and high (HF, approximately 0.25 Hz) frequency. They have been demonstrated to be appropriate indices of, respectively, sympathetic and parasympathetic modulations of heart period. In control subjects, at rest, LF is slightly predominant over HF. In post myocardial infarction patients there is a predominant LF and a diminished HF that suggests an alteration of sympatho-vagal balance with a predominance of sympathetic tone. This approach, by providing indices of sympathetic and vagal neural regulatory outflows, appears adequate to evaluate several pathophysiological conditions such as ischemic heart disease, hypertension or congestive heart failure, which are characterized by important alterations of neural regulatory mechanisms.

Electrocardiography↗
PubMed1991

Primary and salvage chemotherapy in advanced Hodgkin's disease: the Milan Cancer Institute experience.

This paper reviews the most relevant therapeutic results achieved by the Milan Cancer Institute through successive randomized studies in advanced Hodgkin's disease. The experience achieved confirms the therapeutic importance of an anthracycline-containing regimen such as ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) as salvage treatment and as primary chemotherapy, either when combined with irradiation or cyclically alternated with MOPP (mechlorethamine/vincristine/procarbazine/prednisone). Anthracycline-based combinations can be further refined to decrease toxicity. The biologic aspects of drug-sensitive v drug-resistant tumor cells and the accurate definition of prognostic categories at the time of first treatment failure are also discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Prolonged disease-free survival after high-dose sequential chemo-radiotherapy and haemopoietic autologous transplantation in poor prognosis Hodgkin's disease.

Although effective in achieving durable remission in selected tumors incurable by conventional-dose chemotherapy, high-dose regimens requiring bone marrow transplantation remain too toxic for widespread use. With the aim to improve the therapeutic index of high-dose therapy, we have developed a novel program whereby several non-cross-resistant agents (including total body irradiation at myeloablative dose) were delivered sequentially rather than concurrently. The regimen has been tested in 25 patients with Hodgkin's disease refractory to primary chemotherapy (MOPP and ABVD) or relapsed within 12 months after first complete remission. The efficacy of the sequential regimen (72% complete response rate, 49% event-free survival and freedom from progression at four years, with a median observation of 3.5 years for patients remaining alive) compares favorably with the activity so far reported for the most effective high-dose regimens. Toxicity was low; no toxic deaths occurred and only three life-threatening adverse events were documented after autografting. The excellent tolerability of the final myeloablative course most likely reflects the speed and completeness of haematologic recovery that followed the use of peripheral blood progenitors as the sole or additional source of myeloid stem cells. The reduction of haematologic toxicity was further emphasized when rhG-CSF was employed to both shorten post-chemotherapy neutropenic intervals and to collect large amounts of peripheral blood stem cells. We expect that the use of growth factors will have a major impact on the therapeutic index of high-dose regimens. This, in turn, will confirm their safety as primary treatment in selected high-risk subsets.

Adult↗
PubMed1991

Signal averaging of pre- and post-extrasystolic beats in patients with ventricular arrhythmias.

To evaluate the effects of premature ventricular beats on the impulse conduction of adjacent sinus cycles, we compared the high amplification signal-averaged electrocardiogram parameters of the pre- and post-extrasystolic beats with those of the remaining sinus cycle. According to the duration of filtered QRS (fQRS), to the voltage of root mean square of the terminal 40 ms (RMS 40) and to the duration of low amplitude terminal components of the sinus cycles, ventricular late potentials were detected in nine out of 29 subjects. Patients with an abnormal signal-averaged electrocardiogram exhibited a longer fQRS (146 +/- 6 versus 116 +/- 2 ms), a reduced RMS40 voltage (18 +/- 2 versus 80 +/- 10 microV) and a prolonged duration of less than 40 microV components (42 +/- 4 versus 17 +/- 2 ms). Analysis of the pre-extrasystolic beats did not reveal any significant variation in the above parameters, showing a mean difference of 0.44 +/- 2.4 ms; 0.02 +/- 1.14 microV; 1 +/- 1.9 ms and of -1.45 +/- 1.02 ms; 3.5 +/- 8.6 microV; -0.7 +/- 0.84 ms respectively, for patients with and without ventricular late potentials. In addition, no significant variation was observed when the post-extrasystolic beats were considered. These results indicate that the sinus cycles adjacent to premature ventricular discharges do not present variations of signal-averaged electrocardiogram parameters that may suggest an influence of the ectopic beats on their intramyocardial impulse propagation.

Adult↗