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Biomedical subjects

S Di Carlo

Publications and source records attributed to S Di Carlo.

At least 19 recordsLinked to original sources

Neurosedation in dentistry of the disabled patient: the use of midazolam, propofol, and remifentanil.

AIM: This prospective randomized study, deals with neurosedation in dental treatment of 200 disabled patients and unable to cooperate, subdivided in 4 groups of 50 male only patients, with age ranging from 28 to 59 (39+/-11), ASA I-III. METHODS: The pharmaceuticals used were Midazolam (group MID) Propofol (group Prop) and Remifentanil. Midazolam and Propofol were used following a bolus-infusion sequence, both separately and in combination among themselves (MID\PROP group), or with an opioid, Remifentanil (MID\PROP\REMI group). ECG, heart rate , non invasive blood pressure (NIBP), SaO(2), EtCO(2) during the procedure were monitored. Induction time, duration of the sedation, recovery time and discharge were reported. RESULTS: The statistical analysis demonstrated the superiority of the PROP group for induction time in minute (3.1+/-0.5) in comparison with the MID group (10.6+/-2.1), the MID\PROP group (4.3+/-1.3) and MID\PROP\REMI (3.7+/-1.2). The recovery and discharge times have confirmed the superiority of the MID\PROP\REMI group in comparison with the other 3 groups. CONCLUSION: This combination proved best at leveraging the synergistic characteristics of each single pharmaceutical and minimizing the collateral effects of each individually.

Adult↗

Transcutaneous oxygen tension monitoring after successful revascularization in diabetic patients with ischaemic foot ulcers.

OBJECTIVE: To monitor transcutaneous oxygen tension (TcPO2) after percutaneous transluminal angioplasty (PTA) in diabetic patients with ischaemic foot ulcers. RESEARCH DESIGN AND METHODS: Twenty-three diabetic patients with ischaemic foot ulcers who underwent successful revascularization by PTA (SR group) were retrospectively selected. Twenty diabetic patients who underwent unsuccessful revascularization (UR group) were also included. Transcutaneous oxygen tension was measured at the dorsum of the foot before and 1 (+/- 1), 7 (+/- 1), 14 (+/- 1), 21 (+/- 1) and 28 (+/- 1) days after the surgical procedure. RESULTS: After PTA, TcPO2 progressively improved in the SR group, reaching its peak 4 weeks after angioplasty. A concomitant decrease of cutaneous carbon dioxide tension (TcPCO2) was also observed immediately after PTA which reached the lowest levels 3 weeks later. In the UR group, TcPO2 showed a slight improvement immediately after PTA but remained stable throughout the observation, while TcPCO2 levels did not change. Finally, the percentage of SR patients with a TcPO2 > or = 30 mmHg was 38.5% 1 week after PTA, while it increased to 75% 3 weeks later. CONCLUSION: Transcutaneous oxygen tension monitoring showed that after successful revascularization it takes 3-4 weeks for cutaneous oxygenation to improve and reach the optimal levels for wound healing. Transcutaneous carbon dioxide tension monitoring may be more useful to identify the negative outcome of a revascularization procedure. Our findings suggest that, when the surgical approach can be delayed, the best timing to perform a more aggressive debridement or minor amputations is 3-4 weeks after successful revascularization.

Aged↗

Cell-mediated immune response in MDMA users after repeated dose administration: studies in controlled versus noncontrolled settings.

Acute administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") produces time-dependent immune dysfunction in humans. Recreational use of MDMA generally includes repeated drug consumption, often in association with other drugs, such as alcohol and cannabis. In the laboratory setting, repeated MDMA administration to healthy MDMA consumers produced a time-dependent immune dysfunction similar to that observed with the ingestion of a single dose, and the first of the two administrations paralleled the time-course of MDMA-induced cortisol stimulation kinetics and MDMA plasma concentrations. A significant decrease in CD4 T-helper cells with simultaneous increase in natural killer (NK) cell and a decrease in functional responsiveness of lymphocytes to mitogenic stimulation was observed. Response to the second dose was either long-lasting compared with the first dose or disproportionate and did not show any parallelism with cortisol and MDMA plasma concentrations. This circumstance extended the critical period during which immunocompetence is highly impaired as a result of MDMA use. Accumulation of MDMA in the body of a poor metabolizer induced higher immunomodulatory effects with statistically significant differences in NK cell function compared with extensive metabolizers. When basal values of lymphocyte subsets were examined in a population of recreational MDMA users participating in different clinical trials, alterations in several immunological parameters were observed. The absolute number of lymphocytes, in particular T lymphocytes and CD4 T-helper cell subsets, showed a trend toward reduced values, although cell counts were within normal limits. By contrast, NK cells in MDMA consumers were reduced to one-third of those from healthy persons. A statistically significant decrease in affected immune parameters was recorded during a 2-year observation period in a subgroup of recreational MDMA users. These permanent alterations in immunologic homeostasis may result in impairment of general health and subsequent increased susceptibility to infection and immune-related disorders.

Amphetamine-Related Disorders↗

Effects of repeated doses of MDMA ("ecstasy") on cell-mediated immune response in humans.

Cell-mediated immune response after the administration of two repeated doses of 100 mg 3,4-methylenedioxymethamphetamine (MDMA) at 4-hour and 24-hour intervals was evaluated in two randomised, double-blind and cross-over clinical trials conducted in healthy male MDMA consumers. MDMA produced a time-dependent decrease in the CD4/CD8 T-cell ratio due to a decrease in the number of CD4 T-helper cells, a decrease in the functional responsiveness of lymphocytes to mitogenic stimulation, and a simultaneous increase in natural killer cells. In case of two 100 mg MDMA doses given 4 hour apart, immune alterations produced by the first dose were strengthened by the second one. At 24 hours after treatment, statistically significant residual effects were observed for all the altered immune parameters after the administration of two MDMA doses if compared to single dose and placebo. In the second clinical trial, the second 100 mg MDMA dose given 24 hours after the first dose produced immunological changes significantly greater than those induced by the initial drug administration and which seemed to show a delayed onset. Significant residual effects were observed for all the immune parameters as late as 48 hours after the second dose. These results show that repeated administration of MDMA with both a short and a long time interval between doses extends the critical period following MDMA administration, already observed after a single dose, in which immunocompetence is severely compromised.

CD4-CD8 Ratio↗

Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans.

Cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") alone and in combination with ethanol were assessed in a double blind, randomized, crossover, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interval between sessions of 1 week, in which single oral doses of MDMA (100 mg), ethanol (0.8 g/kg), the combination of both drugs, and placebo were tested. Acute MDMA administration produced a time-dependent immune dysfunction in association with serum concentrations of the drug as well as cortisol stimulation kinetics. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio due to a decrease in both the percentage and absolute number of CD4 T-helper cells and simultaneous increase in natural killer (NK) cells. Ethanol consumption produced a decrease in T-helper cells and B lymphocytes. The combination of MDMA and ethanol caused the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cytokines (transforming growth factor-beta and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-gamma) to Th2-type cytokines (interleukin-4 and interleukin-10). Disregulation in the production of pro- and anti-inflammatory cytokines with an unbalance toward anti-inflammatory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immunological homeostasis, if temporarily repeated, might alter the immune response with a risk for the general health status.

Adult↗

Immunomodulating activity of MDMA.

MDMA (3,4-methylenedioxymethamphetamine) use can cause neurochemical, behavioral and endocrine alterations, similar to those produced by exposure to acute stress, suggesting its potential as a "chemical stressor." It is known that stressful stimuli can produce a depression of immune function and an alteration in immune cells distribution. In vitro exposure to MDMA resulted in a modulation of several immune functional parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produced a rapid and sustained suppression of induced lymphocytes proliferation and a significant decrease in circulating lymphocytes. These alterations in rat immune function were accompanied by a significant rapid increase in plasma corticosterone concentrations. It was postulated that the result of altered induced proliferation response of lymphocytes could have been due to a combined effect of direct action of MDMA on lymphocytes and to the activation of the hypothalamic pituitary adrenal axis (HPA axis) and/or the sympathetic nervous system (SNS) via central mechanisms. In humans, acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in CD4+ T-cells and functional responsiveness of lymphocytes to mitogenic stimulation, while percentage of natural killer cells significantly increased. A rise of cortisol plasma concentrations similar to that observed in the rat model supported the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the median eminence of the hypothalamus and subsequent HPA axis and SNS activation. The present findings indicate that MDMA ingestion may represent a potential health hazard for an increased risk of immune system-related diseases.

Animals↗

[Immunomodulator properties of ecstasy (MDMA)].

In vitro exposure to ecstasy (3,4-methylenedioxymethamphetamine, MDMA) alters some immune parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produces a suppression of lympho-proliferation response and a decrease in circulating lymphocytes, accompanied by an increase in plasma corticosterone. It was postulated a direct action of MDMA on lymphocytes or rather an indirect action mediated by the hypothalamic pituitary adrenal axis (HPA-AXIS) and/or the sympathetic nervous system (SNS). Acute MDMA treatment effected on healthy-volunteers produces an immune dysfunction associated with pharmaceutical characteristics and so with MDMA plasma concentrations. There is a decrease in CD4+ T-cells and functional responsiveness of lymphocytes, while percentage of natural killer cells increases. A contemporary rise of cortisol plasma concentrations supports the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the hypothalamus and subsequent HPA-axis and SNS activation.

Animals↗

Immunomodulating properties of MDMA alone and in combination with alcohol: a pilot study.

Cell-mediated immune response after the administration of MDMA alone and in combination with alcohol was evaluated in a randomized, double-blind, double-dummy, cross-over pilot clinical trial conducted in four healthy MDMA consumers who received single oral doses of 75 mg MDMA (n = 2) or 100 mg MDMA (n = 2), alcohol (0.8 mg/kg), MDMA and alcohol, or placebo. Acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio as well as in the percentage of mature T lymphocytes, probably because of a decrease in both the percentage and absolute number of T helper cells. The decrease in CD4 T-cell counts and in the functional responsiveness of lymphocytes to mitogenic stimulation was dose-dependent. The correlation between MDMA pharmacokinetics and the profile of MDMA-induced immune dysfunction suggests that alteration of the immune system may be mediated by the central nervous system. Alcohol consumption produced a decrease in T helper cells, B lymphocytes, and PHA-induced lymphocyte proliferation. Combined MDMA and alcohol produced the greatest suppressive effect on CD4 T-cell count and PHA-stimulated lymphoproliferation. Immune function was partially restored at 24 hours. These results provide the first evidence that recreational use of MDMA alone or in combination with alcohol alters the immunological status.

Adjuvants, Immunologic↗

Cytokine production in saquinavir treated mice.

The effects of chronic and acute saquinavir treatment on murine cytokine production were investigated in both plasma and splenocyte cultures. Cytokine plasma levels were below the detection limit in both saquinavir treated mice and in control mice with the exception of IFN-gamma, whose levels were detectable in 15 day treated mice. Saquinavir was found to increase interferon gamma (IFN-gamma) and interleukin-2 (IL-2) production from stimulated splenocytes. Saquinavir also caused a marked reduction of transforming growth factor-beta 1 (TGF-beta 1) in supernatants of splenocytes cultures. Conversely, interleukin-1 beta (IL-1 beta), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) production was not modified by drug treatment. In the present paper we hypothesized that this protease inhibitor may be involved in the immunoregulatory cytokine network.

Animals↗

Cytokine production in blood mononuclear cells from epileptic patients.

Although convulsive disorders have been associated with immune abnormalities, little is known about cytokine production in epileptic patients. We evaluated the concentrations of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and interleukin-6 (IL-6) secreted by peripheral blood mononuclear cells (PBMC) from epileptic patients. The PBMC collected from epileptic patients, as compared with those of a control group, showed greater production of IL-1 alpha, IL-1 beta, and IL-6 in response to in vitro stimulation with mitogen. There was no statistical difference among patients treated with different antiepileptic drugs (AEDs). Significantly greater IL-2 production was observed in PBMC from carbamazepine (CBZ)-treated patients as compared with both the control group or with valproate and phenobarbital (PB)-treated patients.

Adolescent↗

Modified procedure for labelling target cells in a europium release assay of natural killer cell activity.

Lanthanide europium chelated to diethylenetriaminopentaacetate (EuDTPA) can be used to label target cells such as tumor cells and lymphocytes (Blomberg et al., 1986a,b; Granberg et al., 1988). This procedure has permitted the development of new non-radioactive methods for the detection of target cell cytolysis by natural killer (NK) cells (Blomberg et al., 1986a,b), cytotoxic T lymphocytes (CTL) (Granberg et al., 1988) or complement-mediated cytolysis (Cui et al., 1992). However, we had no success with this method because of a lack of comparability between human NK cell activity simultaneously measured by a classical 51Cr release assay (Seaman et al., 1981) and EuDTPA release assay (Blomberg et al., 1986a). Furthermore, cell division and cell viability were significantly impaired by the suggested concentrations of EuCl3. In this paper, we present a modified non-cytotoxic method for target cell labelling with EuDTPA while cells are growing in culture medium.

Cytotoxicity Tests, Immunologic↗

Macrophage functions in drugs of abuse-treated mice.

The in vivo effect of morphine, methadone and cocaine on murine peritoneal macrophage-mediated cytostasis and macrophage supernatant mediated cytostasis was investigated. In addition, the activity of drugs of abuse was studied on IL-1 alpha and TNF production by activated murine macrophages. A highly depressive effect on macrophage-mediated cytostatic activity and a decrease of IL-1 alpha and TNF levels were found in the supernatants of activated macrophages observed in morphine- and cocaine-treated mice. Conversely, a significant impairment of macrophage functions was not observed in methadone-treated mice. Our results suggest that the inhibition of macrophage defensive functions caused by drugs of abuse may be an important cofactor in the pathogenesis of infectious diseases.

Animals↗

High-performance liquid chromatographic-mass spectrometric assay of busulfan in serum and cerebrospinal fluid.

A liquid chromatographic-mass spectrometric method has been developed to determine busulfan concentrations in the cerebrospinal fluid and serum of some children undergoing bone marrow autotransplantation. After two liquid-liquid extraction steps with dichloromethane on a biological matrix, the separation of busulfan was carried out by isocratic reversed-phase chromatography. The mass spectrometric system was operated in electron-impact mode. Principal ions at m/z 175, 111 and 79 were observed for busulfan, but only m/z 175 was chosen for the quantification of the analyte. The retention time of busulfan was 2.5 min. The detection limit of 100 ng/ml allowed the determination of cerebrospinal fluid and serum busulfan concentrations during the four days of high-dose (1 mg/kg) treatment prior to autotransplantation in five child patients.

Busulfan↗

Immunomodulating properties of carbamazepine in mice.

The protective effects of carbamazepine (CBZ) were studied in mice inoculated with Lewis Lung Carcinoma (3LL), Madison Lung Carcinoma (M109), L5178Y lymphoma, L1210 leukaemia and Candida albicans. There was no significant increase in survival time of mice treated with CBZ. However, CBZ, as well as its metabolite CBZ 10-11 epoxide (CBZ 10-11 EPOX), showed a significant increase in NK-cell activity. CBZ also produced a significant increase of phagocytosis and killing properties of PMNs. There was no significant difference in the stimulation of splenic lymphocyte blastogenesis by different concentrations of phytohaemagglutinina (PHA), observed between the controls and CBZ treated mice. The results demonstrate that the effect of chronic treatment with CBZ on the immune response is a complex phenomenon which remains a challenge for future research.

Adjuvants, Immunologic↗

The social and vocational outcome of spinal cord injury patients.

Functional status, perception of adjustment, occupational outcome and social functioning were investigated in a group of spinal cord injury (SCI) patients (mean age 34, range 10-74 years) seen at a specialised spinal unit over the period January 1984-December 1988. Functional status was assessed using a standardised scale measuring patients' performance of specific tasks, and other measures of outcome were investigated by a structured interview. Almost two thirds (68%) of the patients were independent according to the standardised scale (33% quadriplegic and 84% paraplegic). Patients' autonomy appeared to be threatened by architectural barriers in and about the house: approximately one third (34%) of those classified as 'independent' on the standardised rehabilitation scale used needed some help in their everyday life. A negative occupational outcome emerged: compared to the pre-morbid situation, 43 patients (44%) were worse off; 48 (49%) did not experience substantial changes--though it must be noted that 68% of these (33/48) were virtually unemployed (ie student, home maker, retired, unemployed) before the injury; and for 6 (7%) some improvement took place. With a multivariate analysis age was the only statistically significant predictor of poor occupational outcome, with older patients being worse off irrespective of the extent of disease and functional autonomy. The paper discusses these results and stresses the need for integrating results based on the use of standardised rehabilitation scales with the analysis of potential barriers influencing a patient's ability to exploit his/her autonomy.

Activities of Daily Living↗

Immunological consequences of zidovudine treatment in control and morphine or methadone treated mice.

The effects of acute and chronic zidovudine (AZT) administration on immunologic test responses of mice were studied. The effects of AZT administration combined with morphine or methadone treatment, were also studied separately comparing the effects of each drug. We noted that AZT-treatment did not modify the T-lymphocyte subsets (L3T4/LyT2 rate), whereas morphine-treatment and AZT plus morphine treatment decreased the percentage of T helper cells. Acute and chronic AZT-treatment increased Natural Killer cell (NK) activity and also recovered the decreased NK cell activity produced by morphine-treatment. AZT-treatment, morphine-treatment, AZT plus morphine treatment and AZT plus methadone treatment strongly depressed the phagocytic physiological activity of Polymorphonuclear leukocytes (PMNs). Another evidence of immunologic responsiveness against AZT was the reduction of the mitogenic and antigenic response of lymphocytes. These results suggest a negative role of AZT-treatment especially on phagocytic activity and confirms a depressive effect of morphine-treatment on several immune functions studied. Furthermore, there is no indication of additive or synergistic toxic effects of AZT, morphine and methadone on the immune functions above that seen with each of these drugs when tested alone.

Animals↗

Different prevalence and degree of nonspecific bronchial hyperreactivity between seasonal and perennial rhinitis.

From the patients observed at our respiratory allergology service, we selected patients with rhinitis only, without any past or present respiratory symptoms, for our study. All these patients had normal pulmonary function, were administered carbachol or methacholine bronchial challenges, and had one or more skin reactions to perennial or seasonal allergens. Patients were allocated to three groups: group A, patients with seasonal rhinitis who were administered nonspecific challenges out of season; group B, patients with seasonal rhinitis tested during the season; and group C, patients with perennial rhinitis. The three groups were divided into subgroups according to the duration in years of rhinitis and to the degree of nonspecific bronchial responsiveness. The distribution into four groups of reactivity, arbitrarily defined as normal and mildly, moderately, and severely increased reactivity, was as follows: group A, 124, 21, 30, 22; group B, 75, 15, 7, and 21: and group C, 69, 17, 39, and 72, respectively. The patients of group C (perennial rhinitis) demonstrated a distribution significantly (p less than 0.001) different from subjects with seasonal rhinitis, both group A and group B. Our results are consistent with the hypothesis that perennial rhinitis is much more important than seasonal rhinitis as a risk factor for developing nonspecific bronchial hyperresponsiveness.

Age Factors↗