Memory distortion during acute and chronic pain recalling.

AIM: The aim of this study was to evaluate the presence of pain memory distorsion using different quantitative pain scales. METHODS: A retrospective study on 2333 patients treated in a Pain Therapy Centre from 1994 to 2000 was carried out. VAS and NRS scores have been evaluated, as referred by patients, at the beginning and at the end of treatment. Moreover pain relief has been evaluated by means of correlation between initial and final pain. RESULTS: Patients do not remember initial pain correctly, using both VAS and NRS. CONCLUSION: Pain memory distorsion is related to pain intensity variation during treatment rather than present pain, and it is inversely related to the initial pain intensity. For this reason, it is not correct to evaluate pain relief at the end of treatment since this procedure can under- or over-estimate the initial pain.

Molecular evidence of organ-related transmission of Kaposi sarcoma-associated herpesvirus or human herpesvirus-8 in transplant patients.

In transplant patients, Kaposi sarcoma (KS)-associated herpesvirus or human herpesvirus-8 (HHV-8) infection is associated with the development of KS, primary effusion lymphoma and Castleman disease. Whether HHV-8 is either reactivated in the recipient or transmitted by the donor has been investigated so far only by serologic studies. Thus, we addressed the issue of HHV-8 transmission in the transplantation setting by molecular methods. We exploited the high level variability of the orf-K1 gene and the polymorphism of the orf-73 gene of the HHV-8 genome to assess the genetic relatedness of the HHV-8 strains identified in the posttransplant KS lesions that developed, simultaneously, 20 months after transplantation, in 2 recipients of twin kidneys from the same cadaver donor. The 100% identity of nucleotide sequence of the most variable viral region and the presence of the same, single orf-73 type in both patients provides strong molecular evidence of organ-related transmission of HHV-8 in the setting of transplantation.

Higher plasma catecholamine and metabolite levels in the early phase of nonsegmental vitiligo.

The etiology of vitiligo is still being debated, although neural factors seem to play a pivotal role in its pathogenesis. In our search for a link between vitiligo and the activity of monoaminergic systems, we used high-pressure liquid chromatography and electrochemical detector (HPLC-ED) methods to measure the plasma levels of the following substances in 35 healthy subjects and in 70 patients suffering from nonsegmental vitiligo at the different stages of the disease: catecholamines [norepinephrine (NE), epinephrine (E), and dopamine (DA)], their precursor 3,4-dihydroxyphenylalanine (DOPA), their metabolites [3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NMN), metanephrine (MN), and homovanillic acid (HVA)], and 5-hydroxyindolacetic acid (5-HIAA) as the major metabolite of serotonin. We found that the levels of NE, E, NMN, MN, HVA, and 5-HIAA were significantly higher in patients compared to controls. The patients at an active phase of the disease (n = 49/70) showed significantly higher levels of NE, NMN, MHPG, and HVA than ones at a stable phase. The patients with progressive vitiligo and at its more recent onset (< 1 year) showed significantly increased levels of E, NE, and MN in comparison with longer-term sufferers. No significant differences were observed when the patients were subdivided according to the type of vitiligo or their age at its onset. The higher catecholamine and metabolite levels in the early phase of the disease may reflect increased activity by monoaminergic systems, probably due to stressful events, including the onset of vitiligo itself.

The influence of alprazolam on the monoaminergic neurotransmitter systems in dysthymic patients. Relationship to clinical response.

The effects of alprazolam (1.5 mg/die) on the levels of the monoaminergic neurotransmitter metabolites, on the activity of the hypothalamic-pituitary-adrenal axis and on clinical outcome in subjects with primary late-onset dysthymia were investigated. Drug treatment significantly decreased plasma and urinary cortisol levels, serotonin platelet-bound and urinary 3-methoxy-4-hydroxyphenylglycol concentrations, while it increased plasma homovanillic acid (HVA) concentrations. Significant relationships were observed between neurochemicals and global scores or some items of the Hamilton Depression Rating Scale, before and after treatment. Patients responded positively (73%) to the therapy; clinical outcome was significantly correlated with plasma and urinary HVA levels. Collected data seem to support the hypothesis that central monoaminergic systems are in part involved in therapeutic response to alprazolam.

[Superselective spinal anesthesia for saphenectomy intervention. Comparison of 2 concentrations of hyperbaric bupivacaine]. / Anestesia spinale superselettiva per l'intervento di safenectomia. Confronto fra due concentrazioni di bupivacaina iperbarica.

BACKGROUND: High concentrations of intrathecal local anaesthetics may be neurotoxic. The purpose of this study was to compare the features of superselective spinal anaesthesia (ASS) obtained with an equivalent dose (5 mg) of 0.5% (available now also in Italy) and 1% hyperbaric bupivacaine. METHODS: A prospective study was carried out on 100 patients undergoing saphenectomy, who were randomized into two groups to receive either 0.5% bupivacaine 1 ml (group A) or 1% bupivacaine 0.5 ml (group B). The anaesthetic solution was injected 1 ml/min at L2-L3 with an atraumatic needle. During dural puncture and following 20 minutes patients were held with the operative side down. In every patient were recorded: quality and level of analgesia on dependent (operative) and non dependent sides; motor-block at the 20th minute and 2nd, 3rd and 4th hours on both sides; reduction per cent of systolic artery pressure (SAP) and heart rate (HR), incidence of hypotension (SAP < 90 mmHg) and bradycardia (HR < 50 bts/min); recovery of deambulation and micturition and side effects. RESULTS: Significant differences between the two groups have been found in: 1) number of thoracic segments blocked (3.22 vs 2.02); 2) motor block at the 2nd hour; 3) number of patients able to walk (19 vs 3) and to micturate (11 vs 3) at the 2nd hour. CONCLUSIONS: 0.5% hyperbaric bupivacaine can be successfully use in ASS; early regression of motor block is especially suitable for the requirements of day surgery.

Catecholaminergic, neuroendocrine and anxiety responses to acute psychological stress in healthy subjects: influence of alprazolam administration.

We studied the effect of alprazolam (APZ) in 12 healthy volunteers on the psychological stress-induced activation of emotion and on the pituitary-adrenal, adrenomedullary and sympathoneuronal systems. After 3 days of placebo or APZ (1 mg/day orally) administration, we examined plasma levels of adrenocorticotropic hormone, cortisol, L-3,4 dihydroxyphenylalanine, dopamine, norepinephrine (NE), epinephrine, metanephrine, normetanephrine, homovanillic acid, vanillylmandelic acid, 3-methoxy-4-hydroxy phenyglycol, urinary levels of cortisol and catecholamines, circulatory responses and state anxiety levels in subjects undergoing psychological stress based on viewing horror, violence, danger and war film clips. Film viewing produced modest rises of state anxiety levels, of plasma NE concentration and of diastolic blood pressure in both the placebo and drug groups. APZ significantly reduced anxiety levels at the beginning of the experimental session and caused a decrease of noradrenergic and dopaminergic neurotransmitter and cortisol concentrations. Our data suggest that APZ reduced anxiety related to the expectation of the event, while the circuitry between structures responsible for anxiety and peripheral sympathoneural function was still found to be partly sensitive to film viewing.

Catecholamines in human dental pulp. A combined immunohistochemical and chromatographic study.

Pharmacological studies have suggested that nerve-released catecholamines may play an important role in the regulation of vascular tone and in the modulation of sensory nerve activity in animal teeth. We have used tyrosine hydroxylase-immunohistochemistry to detect catecholamine-producing cells in human dental pulp and high performance liquid chromatography to identify and quantitate catecholamines in this tissue. Tyrosine hydroxylase-immunoreactivity was confined to a sub-population of nerve fibres that were mainly localized around blood vessels. Considerable concentrations of norepinephrine (17.8 +/- 3.75 pg/mg tissue) and much lower concentrations of dopamine and epinephrine (0.27 +/- 0.10 and 0.19 +/- 0.11 pg/mg, respectively) were measured in all samples examined. It is suggested that catecholamines in human dental pulp are exclusively contained in nervous structures that are mainly associated with blood vessels and that norepinephrine is the candidate neurotransmitter of these nerve fibres. These data provide the basis to further studies addressed to clarify the possible functions of catecholamines in human dental pulp during physiological as well as inflammatory situations.

Normal-range plasma catecholamines in patients with generalized and acrofacial vitiligo: preliminary report.

BACKGROUND: There is a body of evidence that neutral factors may play a role in the pathogenesis of vitiligo. OBJECTIVE: We look for the existence of a relationship between vitiligo and monoaminergic systems. METHODS: We use high-pressure liquid chromatography to measure the plasma level of catecholamines, their precursor 3,4-dihydroxyphenylalanine and their metabolites 3-methoxy-4-hydroxy phenylglycol (MHPG), normetanephrine (NMN), metanephrine and homovanillic acid (HVA). Forty patients with the generalized (n = 31) and acrofacial (n = 9) types of vitiligo are studied. RESULTS: Significant differences are not found either between males and females or between the entire group of patients and the controls. HVA and NMN levels significantly correlate with age (r = 0.332, p < 0.05, and r = 0.331, p < 0.05, respectively). Significant correlations are also seen either between noradrenergic or between dopaminergic parameters (norepinephrine vs. MHPG, r = 0.326, p < 0.05; dopamine vs. HVA, r = 0.540, p < 0.01). When the patients are grouped on the basis of vitiligo type or age of disease onset, the plasma mean levels of the neural compounds are always nonsignificantly different from those of the controls. However, both catecholamines and metabolites show higher, although not significant, concentrations in patients with a shorter duration of disease. CONCLUSION: Monoaminergic systems seem unlikely to be related to vitiligo, at least to the generalized and acrofacial types. However, variations cannot be excluded in genetically predisposed individuals during the onset or the active phases of disease.

Dopamine synthesis, uptake and metabolism in embryonic rat mesencephalic cultures.

We have developed an HPLC method using electrochemical detection (ED) to study the synthesis, uptake and metabolism of dopamine (DA) in primary cell cultures dissociated from rat embryonic mesencephalon. The method is rapid and simple and is also able to detect, after 7 days in vitro incubation (DIV), intracellular levels of L-3,4-dihydroxyphenylalanine (L-DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC). The amount of DA synthesized and taken up from the cells is directly proportional to in vitro development time; the contents of endogenous DA is related to the number of mesencephalic neurons originally plated. When the dopa decarboxylase inhibitor alpha-methyldopa is added to the incubation medium, it reduces DA levels and conversely increases the amount of L-DOPA in a dose-dependent manner. In mesencephalic-striatal cocultures a statistically significant increase in the amount of DA is observed. This is not observed when either cerebellar or cortical cells are used in the cocultures which confirms the importance of target striatal cells in the maturation of dopaminergic mesencephalic neurons.

[Peridural anesthesia with 0.5% bupivacaine-fentanyl. Evaluation of the pre-heating effect]. / Anestesia peridurale con bupivacaina 0.5%-fentanil. Valutazione dell'effetto del preriscaldamento.

The effect of preheated (37 degrees C) mixture of 0.5% bupivacaine and fentanyl on peridural anaesthesia have been studied in a double blind randomized clinical trial. Fifty patients of both sexes, ASA I-II, undergoing elective surgery for inguinal hernia repair or radical saphenectomy have been randomly assigned either to the control group (n = 25) receiving 0.5% bupivacaine-fentanyl at room temperature (20 degrees C), or to the group receiving the same anaesthetic mixture preheated for 12 hours up to 37 degrees C (n = 25). The latency period, extension, duration and quality of anaesthetic block were evaluated. A significative difference in the extension of anaesthetic block was detected at 6' (p less than 0.05 for extension up to T10 and T11, p less than 0.025 up to T12), and at 8' (less than 0.05 for extension up to T10). However no difference was observed between the two groups at 10' and later. The use of 0.5% bupivacaine-fentanyl mixture resulted in a short latency period, as previously observed, and its preheating does not seem to affect substantially the parameters evaluated in this study.

[Loco-regional analgesia with continuous peridural technique in labor. Evaluation of 4 years of experience]. / Analgesia loco-regionale con tecnica peridurale continua nel travaglio di parto. Valutazione di 4 anni di attività.

The Authors report on the results of their experience using local-regional analgesia performed with the continuous peridural technique over four years of activity with 503 pregnant women. Protocols used over the years called for morphine-fentanyl association, but bupivacaine 0.25% plus fentanyl and bupivacaine 0.125% plus fentanyl mixtures were then employed. In order to evaluate the efficiency of this procedure, the following data were recorded for each patient undergoing the analgesia: duration of labor prior to the effect of the analgesia; time to reach complete dilatation from a 3 cm dilatation; the length of time of the expulsive phase; manifestation of side effects and complications; vacuum utilization. Furthermore, Apgar scores were taken for all newborn babies at 1st and 5th minutes. The data were then compared with those recorded for a group of women with the same obstetrical characteristics who were not treated with analgesia. The comparison showed that the length of time of the dilatation phase (from 3 to 10 cms) was significantly less in the group of treated patients, while the expulsive phase was basically similar in both groups, thus showing that labor mean time had significantly decreased in the group of patients treated with analgesia. The number of vacuum births was basically the same in both groups and comparable to the data available in the literature. These were practically no side effects or complications. In conclusion, our experience confirms the fact that this method is the most reliable in terms of safety, effectiveness and acceptability on the part of women compared to any other analgesic treatment employed during labor.

Behaviour of urinary D-glucaric acid excretion in surgical patients and anaesthesiology staff acutely exposed to isoflurane and nitrous oxide.

Liver function abnormalities have been observed in humans exposed to anaesthetics inhalation. Furthermore, experimental studies have revealed changes in microsomal enzyme activity caused by inhalation of a variety of anaesthetics. The study was designed to assess liver microsomal enzyme function by means of a simple non-invasive test, i.e., measurement of urinary D-glucaric acid (UDGA) excretion. Three groups of selected subjects were examined: (i) 20 patients undergoing orthopaedic surgery receiving an anesthetic mixture, (ii) 18 workers of an Anesthesiology and Intensive Care Unit, occupationally exposed to anesthetics, (iii) 16 controls. Both in the patients and anesthesiology staff, the post-operative UDGA mean values were significantly increased compared to the pre-operative values. The study shows that the behaviour of UDGA excretion is similar in patients and in anaesthesiology staff. Although it is not possible to clarify the mechanism involved, this finding is regarded as a response of the liver to anaesthetics administration in patients and to both environmental pollution and occupational stress in hospital staff.

Simultaneous measurement of total catecholamines and metanephrines in human urine by liquid chromatography with coulometric detection.

A simple routine method is described for simultaneous assay of total urinary norepinephrine, epinephrine, dopamine, normetanephrine and metanephrine. An internal standard of 3,4 dihydroxybenzylamine is added to the diluted urine and acidic hydrolysis of the conjugates is followed by reverse-phase HPLC separation and coulometric detection in the redox mode. The method is rapid and precise and it has a broad linear working range for all substances making it suitable for clinical analysis. Examples are shown of excretion patterns of catecholamines and metanephrines for healthy subjects and depressed patients.

[D-glucaric acid. A new method proposed to investigate damage from exposure to anesthetic gas and vapors]. / Acido D-Glucarico. Una nuova metodologia proposta per indagare il danno da esposizione a gas e vapori anestetici.

Acute exposure and hepatotoxicity following full anesthetic doses is controversial, despite various experimental trials. On the other hand, microsomial enzyme induction following the chronic use of anesthetic gases and vapours, even with minimal metabolism, has been established. Therefore, there is increasing interest in the field of prevention to develop techniques and instruments to minimize pollution of anesthetic vapours and screening methods to detect early liver-damage. We have evaluated the reliability of D-Glucaric Acid test in monitoring microsomial enzyme induction after anesthesia. We evaluated urinary excretion of D-Glucaric Acid before and after exposure to anesthetic gases in 53 subjects, including medical personnel and patients. Statistical analysis of these data confirm the usefulness of this technique to assess acute liver damage in patients undergoing general anesthesia (postoperative increase of 10.5 microns/l as average value of urinary acid excretion, chi 2 = 9.8; p less than 0.01). This technique is also valuable in demonstrating damage in operating room personnel due to chronic exposure (base values greater than 12 microns/l in anesthesiologists with a 9 microns/l increase at the end of surgical intervention, chi 2 = 8.1; p less than 0.01). Data of patients submitted to local anesthesia are more difficult to interprete. They presented a decrease in acid urinary excretion (less than 10 microns/l; chi 2 = 1.93; p less than 0.2) probably due to hemodynamic changes which occurred during spinal block or due to degree of sedation related to de-afferentation itself.

Aspects of amitriptyline and nortriptyline plasma levels monitoring in depression.

Fifty-nine depressed female inpatients were treated with 100 mg amitriptyline (AMT) IM for 4 weeks. Depression ratings and determinations of the parent drug and nortriptyline (NT) were performed weekly. No direct relationship between plasma AMT + NT concentrations and therapeutic response was apparent, but beneficial therapeutic responses and significantly lower side-effect scores were more frequently noted in subjects with concentrations in the 100-200 ng/ml range. AMT + NT concentrations were significantly correlated with age. No significant difference was found in the number of responders between younger and older subjects with two clinical improvement criteria; however, a significant difference emerged when a third more restrictive clinical outcome criterion was adopted. The implications of the present findings for patient treatment and for the interpretation of previous studies are discussed. The data collected point to a possible usefulness of monitoring AMT and NT plasma levels, even if further investigations are needed.

Noradrenergic output and clinical response in depressed women during amitriptyline therapy.

The measurement of the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) in 59 unipolar depressed women before and during administration of 100 mg amitriptyline (AMT) i.m. daily for four weeks showed that the patients could be divided into high or low MHPG excretors. An analysis of the excretion course of MHPG and 3-methoxy-4-hydroxy mandelic acid during therapy showed, in most patients, a lower urinary excretion of both these noradrenaline (NA) metabolites in comparison with basal values. Therapy also decreased plasma noradrenaline concentrations and blood pressure values both at rest and on orthostatic challenge. Available evidence seems to suggest that AMT administration caused a lower overall noradrenergic output that might be partially responsible for a diminished sympathetic nervous activity. The authors were unable to confirm that the baseline MHPG level can predict the clinical response to antidepressant treatment and they found no significant correlations between changes in bio-chemical or physiological variables and drug plasma concentrations or clinical response. The possibility that depressed patients might be grouped according to their different NA metabolism needs to be validated in a larger patient sample.

Idiopathic hydrocephalic dementia in aging brain the neurosurgical approach.

On the basis of our 16 years' experience, we have treated 36 patients by extrathecal shunt for idiopathic normal pressure hydrocephalus. All patients were submitted to clinical evaluation, neuroradiological, and neuropsychological (Mini Mental Test) tests. Seventy-six per cent of patients showed a significant clinical improvement. No change was found in 24% of them, including two patients who died. In a group of 13 patients we measured the level of main neurotransmitter metabolites (MHPG, HVA, 5-HIAA) in order to evaluate the functional status of encephalic monoaminergic system. If care is taken to make a correct diagnosis and give adequate treatment with a shunt, hydrocephalic dementia has a good prognosis.