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R Amici

Publications and source records attributed to R Amici.

At least 19 recordsLinked to original sources

Risk factors and occurrence of rash in HIV-positive patients not receiving nonnucleoside reverse transcriptase inhibitor: data from a randomized study evaluating use of protease inhibitors in nucleoside-experienced patients with very low CD4 levels (<50 cells/microL).

BACKGROUND: Most of the studies evaluating rash in HIV-positive patients have focused on nonnucleoside reverse transcriptase inhibitors (NNRTI), particularly nevirapine, and little is known about the occurrence of rash and the risk factors for its development in patients receiving regimens not based on NNRTI. METHODS: We evaluated all cases of rash observed during a 48-week randomized multicentre trial in 1251 nucleoside-experienced patients who started treatment with protease inhibitors (ritonavir or indinavir) at CD4 counts below 50 cells/microL. Incidence rates for rash were calculated according to gender, clinical status, age, use of highly active antiretroviral therapy (HAART), Pneumocystis carinii pneumonia (PCP) prophylaxis and use of individual antiretroviral drugs at enrollment. Differences between groups defined according to the above characteristics were tested for statistical significance using the log-rank test in a Kaplan-Meier survival analysis. All factors that gave results in the univariate analyses below the significance level of 0.05 were included in a multivariate analysis using a Cox regression model. RESULTS: During a follow-up period of 9690 person-months, 66 patients (5.3%) developed rash (0.68 events/100 person-months). In the univariate analyses, risk of rash did not differ with trial treatment (indinavir or ritonavir), clinical status, PCP prophylaxis, or age. During follow-up, rash was observed in 7.5% of enrolled women and in 4.5% of enrolled men (P=0.03). Serious rash occurred in 4.5% of enrolled women and in 1.6% of enrolled men (P=0.003). Use of HAART (P<0.001) and inclusion of zidovudine and of zalcitabine in the prescribed regimen (P=0.02) appeared to be associated with a lower risk of rash. In the multivariate analysis, the variables that remained significantly predictive of rash were gender (risk for women compared to men: 1.65, 95% confidence interval (CI): 1.00-2.72, P=0.048) and use of a non-HAART regimen (risk for non-HAART patients compared to HAART: 2.73, 95% CI: 1.49-5.02, P=0.001). CONCLUSIONS: In our study, about 5% of HIV-positive patients who started treatment with protease inhibitors at very low CD4 counts developed rash, generally in the first few weeks after treatment. Risk was significantly higher in women and in patients who did not receive a HAART regimen. Our data indicate that women have a higher risk of rash than men, also with regimens that do not include NNRTI.

Adult↗

REM sleep enhancement due to rhythmical auditory stimulation in the rat.

From a physiological viewpoint, REM sleep (REMS) is a period during which homeostatic physiological regulations are impaired. In the rat, REMS occurs in two forms respectively characterized by episodes separated by long intervals (single REMS episodes) and by episodes which have short intervals and occur in sequences (REMS clusters). Since the partition of REMS in the form of either single or clustered episodes may reveal how the REMS drive and body homeostatic processes interact in the control of REMS occurrence, we have used this approach to clarify the effects of the rhythmical delivery of an auditory stimulus (1000 Hz, 63 or 88 dB, 50 ms, every 20 s), which has been previously observed by different authors to enhance REMS in the absence of a previous sleep deprivation. Stimuli were delivered to pairs of animals and triggered by the occurrence of REMS in one rat (REMS-selective stimulation), whilst the other animal received the same stimulus irrespectively of the stage of the wake-sleep cycle (REMS-unselective stimulation). The results showed that the REMS-selective stimulation did not change the overall amount of REMS, since an increase in the occurrence of REMS clusters was concomitant with a decrease in the occurrence of single REMS episodes. In contrast, under the REMS-unselective stimulation, the total amount of REMS was increased during the second day of stimulation through an increase in the duration of both types of REMS episodes. Since during the REMS-unselective stimulation 87% of the stimuli fell outside REMS (i.e., during the REMS interval), the results show that the occurrence of REMS is more consistently affected when the stimuli are delivered in a period during which homeostatic physiological regulations are fully operant.

Acoustic Stimulation↗

Pattern of REM sleep occurrence in continuous darkness following the exposure to low ambient temperature in the rat.

The occurrence of REM sleep episodes, separated by intervals >3 min (single episodes) and < or =3 min (sequential episodes), was determined in the rat during the recovery (ambient temperature (Ta) 23 degrees C, L period of the LD [12 h:12 h]-cycle), which followed the exposure to low Ta (0 and -10 degrees C) during the D period of the previous LD-cycle, either in normal light (DL) or in continuous darkness (DD). Both exposures were characterized by an almost complete disappearance of REM sleep, whilst the recoveries showed an increase in the amount of REM sleep in the form of sequential episodes, which in DD was particularly prominent and concomitant with a decrease in the amount of REM sleep in the form of single episodes. The initial 2 h-rate of REM sleep occurrence was lower following the exposure to Ta -10 degrees C, than to Ta 0 degrees C. In DD, such an effect was due to the large reduction in the occurrence of sequential REM sleep episodes. A functional correlate of this finding is that the accumulation capacity of a second messenger (cAMP) was found to be lower at the end of the exposure to Ta -10 degrees C, with respect to both the control (Ta 23 degrees C) and the end of exposure to Ta 0 degrees C, in the preoptic-anterior hypothalamus, but not in the cerebral cortex.

Analysis of Variance↗

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

Adult↗

Changes in REM sleep occurrence due to rhythmical auditory stimulation in the rat.

The effects of the rhythmical delivery of an auditory stimulus (1000 Hz, from 50 to 100 dB, 20 ms, every 20 s) on the pattern of rapid eye movement (REM) sleep occurrence was studied in the rat. The stimulation was simultaneously carried out on pairs of rats over 5 consecutive days (10-h recording sessions), during which a tone of increasing intensity (50, 63, 75, 88, 100 dB) was used. In each experimental session, auditory stimulation was triggered by the REM sleep occurrence of one rat (REMS-selective stimulation) whilst the other rat simultaneously received the same stimuli, but during any stage of the wake-sleep cycle (REMS-unselective stimulation). The results showed that the total amount of REM sleep in the 10-h recording session was increased over the 5 days of stimulation in the REMS-unselective group. This effect was due to an increase in the mean duration of REM sleep episodes. However, no significant changes were observed in animals under REMS-selective stimulation, nor in a third group of animals in which the spontaneous evolution of REM sleep occurrence (REMS-spontaneous) was studied. Since 86% of the stimuli under the REMS-unselective auditory stimulation fell outside REM sleep, the result would suggest that REM sleep occurrence is affected when the stimuli are delivered during a time period (i.e. during wakefulness or non-REM sleep) in which it is well known that physiological regulations are fully operant.

Acoustic Stimulation↗

Sodium channel activity and sigma binding of 2-aminopropanamide anticonvulsants.

Sodium channel blocking, anticonvulsant activity, and sigma (sigma) binding of selected leads in a series of alpha-amino amide anticonvulsants were examined. While anticonvulsant compounds were always endowed with low micromolar sodium (Na+) channel site-2 binding, compounds with low site-2 Na+ channel affinity failed to control seizures. No correlation could be drawn with sigma1 binding. Both anticonvulsant and Na+ channel blocking activities were independent of stereochemistry, while sigma1 binding seems to be favoured by an S-configuration on the aminoamide moiety.

Amides↗

Control of REM sleep: an aspect of the regulation of physiological homeostasis.

Since REM sleep is characterized by a suspension of the hypothalamic integration of homeostatic regulations, it has been assumed that the duration of both REM sleep episodes and of the time interval between the end of one episode and the beginning of the following episode may be regulated according to sleep related processes and the homeostatic needs of the organism. A series of studies performed on the rat has shown that REM sleep episodes occur as two basic types: single REM sleep episodes, that are separated by intervals > 3 min and sequential episodes, that are separated by intervals < or = 3 min and appear in a cluster. Moreover, it has been observed that, in this species, a change in REM sleep occurrence is caused by a modification in the number of episodes and not in their duration. With respect to this, sleep deprivation and recovery are characterized by a decrease and an increase, respectively, in the number of sequential REM sleep episodes, but the number of single episodes tends to be kept constant. The central aspects of this kind of regulation have been examined biochemically in the preoptic-anterior hypothalamus, an area involved in the control of autonomic and sleep related processes. The results show that the accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) is impaired, in this region, during sleep deprivation and appears to return to the control levels, during the recovery, with a rate inversely related to the degree of the previous deprivation. Moreover, it has been observed that the systemic administration of DL-propranolol and LiCl reduces cAMP accumulation mainly in the preoptic-anterior hypothalamus; this condition is concomitant with a reduction in REM sleep occurrence.

Animals↗

The influence of a heavy thermal load on REM sleep in the rat.

This study was carried out in order to further test the hypothesis that the occurrence of REM sleep in the rat in the form of episodes separated by long intervals (single REM sleep episodes) and by short intervals (sequential REM sleep episodes) is differently influenced by changes in both sleep and ambient related processes. Rats were studied during the exposure to Ta -10 degrees C for 24 or 48 h and during a 12 h recovery period at laboratory Ta (23 degrees C) following either the first or the second 24 h of cold exposure. The exposure to such a low Ta induced an almost complete abolition of REM sleep which was followed, during recovery, by a marked REM sleep rebound. However, in spite of the larger REM sleep deprivation, the REM sleep rebound was weaker following the 48 h-exposure than that following the exposure for 24 h. The increase in the amount of REM sleep during the recovery period was due to an increase in the amount of that occurring in the form of sequential episodes, whilst that in the form of single episodes did not change with respect to control levels. However, the occurrence of REM sleep in the form of sequential episodes was partially impaired during the REM sleep rebound observed in the recovery period following the 48 h-exposure. These results would suggest that the homeostatic regulation of physiological variables may conflict with that of REM sleep occurrence and that the degree of such a contrast is indicated, at low Ta, by the amount of REM sleep in the form of single episodes and, during the following recovery, by the amount of REM sleep in the form of sequential episodes.

Animals↗

The capacity to accumulate cyclic AMP in the preoptic-anterior hypothalamic area of the rat is affected by the exposition to low ambient temperature and the subsequent recovery.

The accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) was measured in the preopticanterior hypothalamic area, the cerebral cortex, and the hippocampus of rats exposed to different ambient temperatures: (1) 23 +/- 0.5 degrees C, for 53 h +/- 20 min (control); (2) -10 +/- 1 degrees C, for 53 h +/- 20 min (exposure to low ambient temperature); (3) -10 degrees C for 48 h and 23 degrees C for the following 5 h +/- 20 min (recovery). The capacity to accumulate cAMP was tested by subjecting animals to acute hypoxia, a stimulus which is known to induce a large increase in brain cAMP concentration. In the control condition, hypoxic stimulation increases cAMP concentration in all the brain regions studied. In contrast, during the exposure to low ambient temperature, whilst both the cerebral cortex and the hippocampus show the same levels of accumulation found in the control condition, cAMP accumulation is reduced in the preoptic-anterior hypothalamic area. However, during the first few hours of the recovery period, the preoptic-anterior hypothalamic area is able to reattain the capacity for cAMP accumulation observed in the control condition.

Animals↗

cAMP accumulation in the hypothalamus, cerebral cortex, pineal gland and brown fat across the wake-sleep cycle of the rat exposed to different ambient temperatures.

The concentration of adenosine 3':5' cyclic monophosphate (cAMP) was determined in the anteroventro-medial hypothalamus, the cerebral cortex, the pineal gland and the interscapular brown adipose tissue, during the different stages of the wake-sleep cycle of rats kept, under a 12-12-h light-dark cycle, in different environmental conditions, i.e., control (47-52 h at ambient temperature (Ta) 23 +/- 0.5 degrees C), exposure (47-52 h at Ta 0 +/- 1 degree C) and recovery (1-4 h at Ta 23 degrees C after 48 h at Ta 0 degree C). The results show that cAMP concentration consistently changed: (1) during the wake-sleep cycle in the anteroventro-medial hypothalamus, decreasing from wakefulness to sleep; (2) during the dark-light transition in the pineal gland, increasing with the onset of the light phase; and (3) with the environmental condition in the interscapular brown adipose tissue increasing, with respect to the control condition, in exposure and recovery. No significant changes in cAMP concentration were observed in the cerebral cortex.

Adipose Tissue, Brown↗

Pattern of desynchronized sleep during deprivation and recovery induced in the rat by changes in ambient temperature.

The pattern of desynchronized sleep (DS) occurrence in the rat was studied during exposure to an ambient temperature (Ta) of 0 degrees C for 48 h and during a 12 h recovery period at laboratory Ta (23 degrees C) following the first and second 24 h of cold exposure. The exposure to low Ta induces a DS deprivation which is followed, during recovery, by a clear DS rebound. Both the decrease and the following increase in the amount of DS are due to changes in the frequency rather than in the duration of DS episodes. The frequency distribution of the intervals between the end of one DS episode and the beginning of the next (DS interval) has shown that two populations of DS intervals exist, i.e. short DS intervals (</=3 min) and long DS intervals (>3 min). On the basis of this, two types of DS episodes have been identified: the 'single DS episode', which is both preceded and followed by a long DS interval, and the 'sequential DS episode', which is a DS episode occurring within a cluster or a sequence of DS episodes and is characteristically separated by short DS intervals. The occurrence of such sequential DS episodes in a 'DS cluster', allows a high amount of DS to occur without increasing the duration of the DS episode. DS clusters are repressed during cold exposure, when the DS drive is counteracted by the need to thermoregulate, and enhanced during recovery, when the DS drive is unrestrained. In contrast, the occurrence of single DS episodes is much less affected by such different experimental conditions.

Journal Article↗

[Propafenone and verapamil poisoning. Report of 2 clinical cases].

We described the self-poisoning of two young adolescents who took improper doses of two major cardiovascular drugs: propafenone and verapamil. The young girls developed markedly different clinical patterns: ECG abnormalities without clinical consequences were found in one case progressively ingravescent ECG abnormalities leading to cardiac arrest in the other. These differences are probably due to varying doses taken and metabolic states. Conventional detoxication and resuscitation techniques proved successful in both cases.

Adolescent↗

[Prevalence of some cardiovascular risk factors in a sample of the aged population].

The distribution of some cardiovascular risk factors in a cohort of elderly population is reported. The study population consisted of 427 males aged 71-91, examined in 1991 and belonging to the Italian rural section of the Seven Countries Study on Cardiovascular Diseases. Systolic blood pressure shows an increasing trend with age, with mean levels greater than 160 mmHg in each quinquennium, while the prevalence of hypertension ranges between 60 and 75%. Other risk factors considered such as serum cholesterol, triglycerides, weight, height and smoking habit show decreasing levels with ageing. This trend is clear also for fasting glucose from the age group 76-80.

Age Factors↗

Ultradian and circadian changes in the cAMP concentration in the preoptic region of the rat.

The concentration of adenosine 3',5'-cyclic monophosphate was measured, during the wake-sleep cycle, in the preoptic region and the cerebral cortex of rats kept in normal laboratory conditions (ambient temperature 22 +/- 0.5 degrees C, 12 h:12 h light-dark cycle) and, during wakefulness, in the preoptic region of rats exposed to extended light and dark periods (i.e. dark in the light hours of the normal photoperiod, and light in the dark hours of the normal photoperiod). The results show that the concentration of cAMP in the preoptic region changes according to the ultradian wake-sleep cyclic, decreasing from wakefulness, through synchronized sleep and to desynchronized sleep. This pattern of change was found to occur both in light and dark hours, however, in the dark hours the levels of preoptic cAMP are higher than those observed in the light hours. In contrast, no significant modification in cAMP concentration was found in the cerebral cortex. In the extended light and dark periods preoptic cAMP concentration increases above the levels found during wakefulness in normal photoperiods. These results show that preoptic cAMP concentration is influenced by ultradian and circadian factors which also appear to be related to sleep processes.

Activity Cycles↗

The short-term effects of dl-propranolol on the wake-sleep cycle of the rat are related to selective changes in preoptic cyclic AMP concentration.

The short-term effects of the intraperitoneal administration of dl-propranolol on the wake-sleep cycle of the rat were studied in relation to the cyclic AMP concentration in the preoptic region and cerebral cortex. The results show that propranolol, but not saline, affected all stages of the wake-sleep cycle, increasing wakefulness, decreasing synchronized sleep and abolishing desynchronized sleep. These effects were associated with a decrement in cyclic AMP concentration both in wakefulness and synchronized sleep. However, this decrement was relatively larger in the preoptic region than in the cerebral cortex. The effects of the drug on cyclic AMP accumulation were also studied in hypoxia, a condition of unspecific brain stimulation. In this condition, the cyclic AMP concentration in both brain regions was found to be higher than that observed during either wakefulness or synchronized sleep. In the hypoxic condition propranolol was found to decrease the nucleotide concentration to the same levels observed in wakefulness and synchronized sleep following its administration. However, no difference in the relative magnitude of the decrement was found between the preoptic region and the cerebral cortex. These findings suggest that in both brain regions the drug acts on a cyclic AMP accumulating system, which may be defined as propranolol-sensitive. The activity of the propranolol-sensitive system in the preoptic region would appear to be related to wake-sleep processes.

Animals↗

Relationship between cAMP concentration in anterior hypothalamic-preoptic region and the ultradian wake-sleep cycle.

In the rat anterior hypothalamic-preoptic region adenosine 3':5'-cyclic monophosphate concentration changes during the ultradian wake-sleep cycle. The administration of DL-propranolol and the exposure to low ambient temperature decreased the nucleotide concentration and also modified the wake-sleep cycle. This suggests that in this region a biochemical correlation exists with different functional states.

Activity Cycles↗

[Aneurysm of the interatrial septum. Description of a case].

Echocardiography (M-mode and 2-dimensional) has identified unusual cardiac anomalies which, not related with cardiac murmurs or clicks or other clinical marks, had not been elsewhere discovered. Among them there is the atrial septal aneurysm, which often occurs with other cardiac malformations (congenital or acquired), but sometimes occurs as an isolated abnormality. The Authors report a case of isolated atrial septal aneurysm, detected in a 6 year-old boy.

Cardiomyopathies↗