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Biomedical subjects

F Lombardi

Publications and source records attributed to F Lombardi.

At least 145 records · Page 8Linked to original sources

Advanced neuroblastoma: results of two treatment programs including sequential hemibody irradiation.

Results of two consecutive treatment programs for advanced neuroblastoma, including sequential hemibody irradiation, are analyzed and compared. The first treatment program (I-TP) included one single-fraction (7 Gy) irradiation to the upper and lower halves of the body as consolidation of remission achieved by previous chemotherapy with CDDP and VP16. A fractionated technique (2 Gy daily for 4 consecutive days to each hemibody) was used in the second treatment program (II-TP) for children in remission following a combination of CDDP + VP16 and ADM + VCR + CTX. In both treatment programs, chemotherapy was continued according to the same pre-radiation regimen following the two sessions of hemibody irradiation. Overall response rate to pre-radiation chemotherapy was 84% and 60% for I-TP and II-TP, respectively. Thirty-month overall progression-free survival was 0 for I-TP and 20% for II-TP. No treatment-related fatalities occurred. In the subsets of patients who reached complete or good partial remission during the pre-radiation chemotherapeutic phase, 30-month progression-free survival in I-TP and II-TP was 0 and 33%, respectively. The role of fractionated hemibody irradiation in prolonging the progression-free survival can be inferred.

Adolescent↗

Premature ventricular contractions and reflex sympathetic activation in cats.

In 27 decerebrate cats under various experimental conditions, we studied the effects of programmed premature ventricular contractions on the impulse activity of preganglionic sympathetic fibres isolated from the third left thoracic ramus. Single extrastimuli increased the sympathetic discharge by 319(SEM 43)% [from 10.3(1.7) to 36(3.7) imp.s-1, p less than 0.05]. The neural response was significantly enhanced after bilateral vagotomy by 394(34)% [from 12(2.6) to 53.3(9.8) imp.s-1, p less than 0.05], but abolished when the stimuli were delivered during bilateral carotid artery occlusion. No sympathetic reflex response was observed in cats with chronic sino-aortic denervation. In eight cats, during occlusion of the left anterior descending coronary artery, the control sympathetic response was progressively and reversibly attenuated from 239(28)% to 36(14)%, at 90 s from the beginning of the occlusion. After bilateral vagotomy, this inhibitory interaction was no longer present and the sympathetic neural response to programmed stimulation was maintained throughout the occlusion period. The data indicate that the sympathetic reflex response initiated by baroreceptive deactivation could be attenuated by cardiac vagal afferent activity induced by coronary occlusion.

Animals↗

Circadian changes in vascular sympathetic activity in ambulant subjects.

In 10 ambulant subjects we studied the circadian changes in sympathetic vasomotor control as assessed by the spectral power of the 0.1-Hz low-frequency component of systolic arterial pressure variability measured with a Millar phi 3F tip transducer. The low-frequency component was higher during the daytime, while the subjects were performing light physical activity, and lower during the night, thus paralleling the circadian systolic blood pressure pattern. However, the morning low-frequency rise preceded the blood pressure increase by about 3 h, suggesting that vasometer control and blood pressure control are at least partly related to different mechanisms.

Adult↗

Restraining effect of captopril on cardiovascular sympathetic efferent neural activity.

In 13 decerebrate cats we studied the effects of captopril (10 mg/kg, intravenous bolus) on the background cardiac preganglionic sympathetic discharge and on its responsiveness to brief baroreceptor deactivations induced by premature ventricular contractions. Captopril caused a significant reduction of 57 +/- 7% (from 2.4 +/- 0.4 impulses/0.1s) in sympathetic discharge, with a mean latency of 35 +/- 3 min from the time of drug administration. In addition, the increase in cardiac sympathetic firing during premature ventricular contractions was markedly reduced, from 257 +/- 30% to 70 +/- 17%, before and after administration of captopril. These data indicate that captopril is not only likely to inhibit sympathetic discharge to the heart, but is also likely to restrain the excitatory sympathetic responses to baroreceptor deactivation.

Animals↗

[Treatment technic and clinical dosimetry in whole-body irradiation].

At the Istituto Nazionale Tumori, Milan, total-body irradiation (TBI) is delivered by a 15 MV linear accelerator, with two lateral opposed beams. Maximum build-up at the skin is achieved by lateral slabs of perspex 3 cm thick. Attenuation filters or bolus are used for dose compensation, or reduction, to the head and lungs. The dose delivered to clinically relevant anatomic regions is determined by "in vivo" dosimetry. For this purpose, calibrated diodes are employed, which are positioned at the entrance and at the exit of the beams. "In vivo" dosimetry data show our TBI technique to allow an homogeneous irradiation of all body areas, with maximum deviation of the mean dose value from reference point dose of -11% in the posterior abdomen, at the spinal cord shielded by arms.

Humans↗

Cisplatin (P) versus cyclophosphamide, adriamycin and cisplatin (CAP) for stage III-IV epithelial ovarian carcinoma: a prospective randomized trial.

In 1982 a randomized trial was started to compare a cisplatin-containing polychemotherapy (CAP: cyclophosphamide - CPA 750 mg/m2, adriamycin - ADM 50 mg/m2, cisplatin - P 50 mg/m2 on day 1 every 21 days) with full-dose cisplatin as single agent (P 60 mg/m2/day on days 1 and 2 every 28 days) in 44 patients undergoing exploratory laparotomy or debulking surgery for stage III-IV epithelial ovarian carcinoma with residual disease greater than 5 cm. The response was evaluated at second-look surgery with random biopsies and peritoneal washing. On the basis of the final results the authors underline some data which, although merely indicative (because of the small number of patients) appear to be worth considering since they are in accordance with the latest reports: a) similar response rate (CR + PR = 47%) to first-line treatment in the two groups; b) the CAP treatment may achieve a longer median duration of CRs than the P treatment (20 versus 11 months); c) overall survival seems similar in the two groups of patients (19 versus 18 months), whereas the survival of CRs seems longer in the CAP treated patients (greater than 32 versus 25 months). The authors also discuss some observations on a possible salvage therapy.

Adult↗

Determination of hydroxylamine traces in propionohydroxamic acid bulk drug and pharmaceutical preparations by capillary gas chromatography.

A specific, sensitive, accurate, and precise capillary gas chromatographic assay for determining trace levels of hydroxylamine, a well-known mutagen, in propionohydroxamic acid bulk drug and oral preparations is described. The analytical procedure involves derivatization in a nonaqueous medium with cyclohexanone and use of an internal standard. The derivative is then determined by capillary GC with a cool on-column injector and a nitrogen-selective detector. Effects of different matrices on the measurement were also determined. The lower limit of quantitation was 7 ppm, and the response was linear from 10 to 260 ppm. The procedure is simple and rapid enough for routine purposes.

Capsules↗

Spectral analysis of heart rate variability in the assessment of autonomic diabetic neuropathy.

We studied heart rate variability in 49 uncomplicated diabetics (27 with insulin therapy; 22 with oral hypoglycemic agents) and in 40 age-matched controls. An automatic autoregressive algorithm was used to compute the power spectral density (PSD) of beat by beat RR variability derived from the surface ECG. The PSD contains two major components (a low frequency approximately 0.1 Hz (LF) and a high frequency, respiratory linked, approximately 0.25 Hz (HF] that provide, respectively, quantitative markers of sympathetic and vagal modulatory activities and of their balance. As compared to controls, in diabetics, besides a reduced RR variance at rest (2722 +/- 300 and 1436 +/- 241 ms2, respectively), we observed during passive tilt an altered response of spectral indices of sympathetic activation and vagal withdrawal, suggestive of a complex modification in the neural control activities. In addition, we compared this approach to the commonly used clinical tests score, and observed that the latter provides overall results similar to those obtained with spectral changes induced by tilt (r = 0.42; P less than 0.01). Of potential clinical importance is that the data obtained with spectral analysis appear more thoroughly quantifiable and do not require the active collaboration of the patients.

Adolescent↗

Sympathetic predominance in essential hypertension: a study employing spectral analysis of heart rate variability.

In this study on 91 subjects we tested the hypothesis of an enhanced sympathetic activity in uncomplicated essential hypertension employing spectral analysis of heart rate variability. With this technique the tonic sympathetic and vagal activities and their changes are respectively assessed by the power of approximately 0.1 Hz (low frequency, LF) and approximately 0.25 Hz (respiratory linked, high frequency, HF) components of the spectrum of the beat by beat variability of RR interval. When comparing the 40 subjects with diastolic blood pressure consistently greater than 95 mmHg (hypertensives, Ht), with 35 age-matched controls (diastolic arterial pressure less than 90 mmHg, Nt), we observed that LF was greater and HF smaller in Ht as compared to Nt, thus suggesting an enhanced sympathetic activity and a reduce vagal activity in Ht. Additionally, passive tilt, which in Nt enhances LF [delta = 26 +/- 2 normalized units (nu)] and reduces HF (delta = -22 +/- 2, nu), produced smaller (P less than 0.05) changes in Ht (delta LF = 6.3 +/- 2.7 and delta HF = -7.5 +/- 2.3 nu). Furthermore, the values of LF at rest and the altered effects of tilt on LF and HF were significantly correlated with the degree of the hypertensive state. Chronic beta-adrenergic blockade (atenolol 100 mg once daily for 2 weeks, n = 13) reduced heart rate and blood pressure (from 162/103 to 136/88 mmHg) together with a significant diminution of LF and an increase of HF. Thus, spectral analysis of RR variability appears to be a convenient non-invasive technique to follow the progressive alterations in sympatho-vagal balance present in essential hypertension.

Adult↗

Combined radiotherapy and chemotherapy in stage T3 and T4 nasopharyngeal carcinoma in children.

Twelve children younger than 16 years affected by undifferentiated nasopharyngeal carcinoma (NPC) with advanced primary tumor (T3, T4) were treated with chemotherapy consisting of Adriamycin (ADM [doxorubicin; Adria Laboratories, Columbus, OH]), vincristine (VCR), and cyclophosphamide (CYC), and radiotherapy. Preradiation chemotherapy produced partial responses in eight of ten evaluable patients. Eleven of 12 patients achieved a complete response following radiotherapy. The actuarial 3-year continuous relapse-free survival (CRFS) was 75%. This represents a significant improvement when compared with the 8% rate obtained in a previous series of patients treated with radiotherapy either with or without adjuvant CYC.

Adolescent↗

Heart rate variability as an index of sympathovagal interaction after acute myocardial infarction.

By analysis of spectral components of heart rate variability, sympathovagal interaction was assessed in patients after acute myocardial infarction (AMI). At 2 weeks after AMI (n = 70), the low-frequency component was significantly greater (69 +/- 2 vs 53 +/- 3 normalized units [NU], p less than 0.05) and the high-frequency component was significantly smaller (17 +/- 1 vs 35 +/- 3 NU) than in 26 age-matched control subjects. This difference was likely to reflect an alteration of sympathovagal regulatory outflows with a predominance of sympathetic activity. At 6 (n = 33) and 12 (n = 29) months after AMI, a progressive decrease in the low- (62 +/- 2 and 54 +/- 3 NU) and an increase in the high-frequency (23 +/- 2 and 30 +/- 2 NU) spectral components was observed, which suggested a normalization of sympathovagal interaction. An increase in sympathetic efferent activity induced by tilt did not further modify the low-frequency spectral component (78 +/- 3 vs 74 +/- 3 NU) in a subgroup of 24 patients at 2 weeks after AMI. Instead, 1 year after AMI, this maneuver was accompanied by an increase in the low-frequency component (77 +/- 3 vs 53 +/- 3 NU, p less than 0.05) of a magnitude similar to the one observed in control subjects (78 +/- 3 vs 53 +/- 3 NU). These data indicate that the sympathetic predominance that is detectable 2 weeks after AMI is followed by recovery of vagal tone and a normalization of sympathovagal interaction, not only during resting conditions, but also in response to a sympathetic stimulus.

Adult↗

Bone sarcomas linked to radiotherapy and chemotherapy in children.

We estimated the risk of subsequent bone cancer among 9170 patients who had survived two or more years after the diagnosis of a cancer in childhood. As compared with the general population, the patients had a relative risk of 133 (95 percent confidence interval, 98 to 176) and a mean (+/- SE) 20-year cumulative risk of 2.8 +/- 0.7 percent. Detailed data on treatment were obtained on 64 patients in whom bone cancer developed after childhood cancer. As compared with 209 matched controls who had survived cancer in childhood but who did not have bone cancer later, patients who had had radiation therapy had a 2.7-fold risk (95 percent confidence interval, 1.0 to 7.7) and a sharp dose-response gradient reaching a 40-fold risk after doses to the bone of more than 6000 rad. The relative dose-response effect among patients who had been treated for retinoblastoma resembled that among patients with all other types of initial tumors, although the cumulative risk of bone cancer in the retinoblastoma group was higher. Similar numbers of patients were treated with orthovoltage and megavoltage; the patterns of risk among categories of doses did not differ according to the type of voltage. After adjustment for radiation therapy, treatment with alkylating agents was also linked to bone cancer (relative risk, 4.7; 95 percent confidence interval, 1.0 to 22.3), with the risk increasing as cumulative drug exposure rose. We conclude that both radiotherapy and chemotherapy with alkylating agents for childhood cancer increase the subsequent risk of bone cancer.

Alkylating Agents↗

Paralytic poliomyelitis in Italy (1981-85).

Fifteen cases of presumptive poliomyelitis occurring in Italy between 1981-85 were studied in order to differentiate between paralysis caused by poliovirus and that of different etiology. Out of seven confirmed cases three were "temporally associated with vaccination". Three aspects are discussed: the need for a careful differential diagnosis of paralytic cases; the over concern about the problem of vaccine-associated cases: the risk connected with re-importation of wild poliovirus strains.

Child, Preschool↗

Heart rate variability signal processing: a quantitative approach as an aid to diagnosis in cardiovascular pathologies.

The heart rate variability (HRV) signal carries important information about the systems controlling heat rate and blood pressure, mainly elicited by autonomic nervous system (sympathetic and parasympathetic) controls. The present paper illustrates methods of HRV signal processing by using autoregressive (AR) modeling and power spectral density estimate. The information enhanced in this way seems to be particularly sensitive in discriminating various cardiovascular pathologies (hypertension, myocardial infarction, diabetic neuropathy, etc.). This method provides a simple non-invasive analysis, based on the processing of spontaneous oscillations in heart rate. Particular emphasis is directed to the algorithms used and to their direct application by using proper computerized techniques: only a few paradigmatical examples will be illustrated as preliminary results.

Cardiovascular Diseases↗

Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma.

Serum CA 125 was measured in 100 patients with ovarian epithelial carcinoma at diagnosis and in follow-up. Levels over 35 U/ml were found in 43 (75.4%) of 57 cases at diagnosis and in 21 (48.8%) of 43 cases in follow-up. A correlation was found between tumor burden and marker positivity: advanced Stages (III and IV) and recurrences had 84.2 and 91% of positivity, compared to 59.1% in early disease (Stages I and II). Analysis by histotype and FIGO grade revealed a difference between the mucinous type and the others and a positive association with less differentiated tumors. In the 30 patients submitted to second-look laparotomy a correlation was found between CA 125 levels and pathological response in 86.7% of cases. This ovarian cancer marker may thus be more useful in monitoring the response to treatment and in long-term follow-up than in diagnosis.

Antigens, Neoplasm↗

Effects of sympathetic activation on ventricular ectopic beats in subjects with and without evidence of organic heart disease.

In a selected group of 10 apparently healthy subjects and 22 patients with organic heart disease, all with frequent ventricular ectopic beats on Holter monitoring, we assessed the influence of sympathetic activation by comparing the arrhythmogenic effects of a symptom-limited bicycle exercise stress test and 90 degree head up tilt. Tilting reduced ventricular arrhythmias in the normal subjects (-48 +/- 18% from 9 +/- 2 beats min-1, P less than 0.05). Exercise stress testing caused small and insignificant changes in arrhythmias during the early (50-75 W) phases and an almost complete suppression of ventricular ectopic beats in the final stages (-99 +/- 1%, P less than 0.01). In six of the 10 subjects, ventricular arrhythmias reappeared in the early recovery phase. In the 22 patients with organic heart disease, tilting increased ventricular ectopic beats (43 +/- 17% from 9 +/- 3 beats min-1, P less than 0.05); augmented repetitive forms in 12 patients (179 +/- 88% from 1.4 +/- 0.6 per 3 min) and produced repetitive forms in six of the 10 remaining patients who did not show repetitive forms during control conditions. Exercise stress testing caused a marked increase in ectopic activity in the early phase (84 +/- 35%) while the response during the maximal phase of exercise as well as during recovery was related to the effort capabilities. Arrhythmias were increased in 12 patients with limited exercise duration and were reduced in 10 patients with good exercise tolerance. These data indicate that sympathetic activation has different effects on ventricular arrhythmias depending on the clinical setting and that tilting is a useful maneuver to evaluate the arrhythmogenic effects of increased sympathetic activity.

Adult↗

Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat.

Brain serotoninergic neurons are known to participate in cardiovascular regulation. Administration of the serotonin precursor 5-l-hydroxytryptophan in conjunction with the monamine oxidase inhibitor phenelzine and the selective peripheral l-amino acid decarboxylase inhibitor carbidopa has been shown to raise the repetitive extrasystole threshold in the canine heart. The present investigation demonstrates that this drug regimen increases the cerebrospinal fluid concentration of serotonin and its major metabolite, 5-hydroxyindoleacetic acid, by 330 and 830%, respectively. By contrast, cerebrospinal fluid concentrations of norepinephrine and its major brain metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate, and of dopamine's metabolite, 3, 4-dihydroxyphenylacetic acid, were not significantly altered. Concomitantly, the ventricular fibrillation threshold was elevated by 42% and the effective refractory period prolonged by 7%. Efferent sympathetic neural activity was suppressed in the normal heart (from 7.9 +/- 1.3 to 3.9 +/- 1.1 impulses/s). The surge in sympathetic activity associated with acute myocardial ischemia was markedly attenuated. These results indicate that enhancement of central serotoninergic neurotransmission can reduce the susceptibility to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.

3,4-Dihydroxyphenylacetic Acid↗

Attenuation of baroreceptive mechanisms by cardiovascular sympathetic afferent fibers.

By sectioning spinal dorsal roots from C8 to T6, we analyzed the contribution of sympathetic cardiovascular afferent fibers to the reflex bradycardia induced by arterial pressure rises in 24 anesthetized and in 21 decerebrate cats. In anesthetized cats, the reflex bradycardia was obtained in 16 animals with occlusions of the thoracic aorta and in 8 animals with phenylephrine injections (25-75 micrograms/kg). In both experimental conditions, the dorsal root section enhanced the bradycardia response, which thus increased from 15 +/- 3 to 20 +/- 3% during aortic constrictions and from 11 +/- 3 to 19 +/- 6% during phenylephrine injections (P less than 0.05). The enhancement, after rhizotomy of the reflex bradycardia during aortic occlusion, was more pronounced in eleven decerebrate cats as it increased from 21 +/- 4 to 34 +/- 4%, P less than 0.05. In five vagotomized and decerebrate cats, the reflex bradycardia was also increased after rhizotomy despite the overall reduction of the reflex response. In five decerebrate cats with beta-adrenergic receptor blockade (propranolol 0.2-0.4 mg/kg iv), aortic occlusion resulted in a small reduction in heart rate which was not significantly affected by dorsal root section. Our data indicate that excitatory reflexes mediated by dorsal roots are likely to modulate the inhibitory supraspinal reflexes that determine the heart rate reduction during acute rises in arterial blood pressure.

Adrenergic beta-Antagonists↗