Demographical and clinical indices for long-term evolution of patients in vegetative or in minimally conscious state.

Objective. To evaluate the prognostic value of demographical, anamnestic, and clinical findings on long-term outcome (up to 36 months) in individuals with severe brain injury in vegetative state (VS) or in minimally conscious state (MCS).Participants. Patients (N = 216) in VS (N = 159) or in MCS (N = 57) consecutively admitted to a neurorehabilitation unit within 1-3 months after severe anoxic (n = 71), vascular (n = 96), or traumatic (n = 49) brain injury.Main outcome. Mortality and improvements in clinical diagnosis at 12, 24, and 36 months after brain injury. Multivariable logistic regression analyses were performed to verify independent relationships of variables collected at study entry with outcome measures.Results. In patients in VS, at the 12-month follow-up, higher level of responsiveness assessed by the Coma Recovery Scale-Revised (CRS-R) total scores at study entry predicted a higher likelihood of both survival and clinical improvement, whereas younger age predicted survival only. At 24 months, female sex and higher CRS-R total scores tended to be associated with clinical improvements. In patients in MCS, younger age and female predicted consciousness recovery at 12 months.Conclusions. Several patients' features easy to collect in rehabilitation setting might help clinicians in prognostication of long-term mortality and clinical evolution of VS and MCS.

Prevalence of Dio2(T92A) polymorphism and its association with thyroid autoimmunity.

The 3,5,3'-L-triiodothyronine (T3) partly derives by the deiodination of the prohormone 3,5,3',5'-L-tetraiodothyronine (T4) by the type 2 iodothyronine deiodinase (D2). The single-nucleotide polymorphism in the D2 gene at position 92 (Dio(2T92A)), generates an enzyme with a reduced T4 to T3 conversion velocity. Because thyroid hormones can modulate the immune response, we hypothesized a pathophysiological role for Dio(2T92A) polymorphism in autoimmunity. The objective of this study was to investigate the Dio(2T92A) polymorphism in relation to thyroid autoimmunity (TA). We compared the prevalence of Dio(2T92A) polymorphism and serum thyroid hormone levels in healthy subjects and subjects with TA. A total of 110 subjects with TA and 106 controls were genotypized for Dio(2T92A) polymorphism. Free T3 (FT3), free T4 (FT4) and TSH were measured and compared with the Dio(2T92A) polymorphism. Dio(292T/A), Dio(292A/A), and Dio(292T/T) healthy subjects were 40.9%, 46.4%, and 12.7%, respectively. These prevalences were similar to those of some European countries whilst significantly different from that of Brazil. In the two groups of healthy subjects and TA subjects, Dio(2T92A) polymorphism had a similar distribution with non-significant differences. Similarly, no significant differences were observed in the serum concentration of FT3, FT4, and TSH between subjects with different Dio(2T92A) polymorphism. The FT4/FT3, and TSH/FT3 ratios were higher in Dio(292T/T) than in Dio(292T/A) and Dio(292A/A) subjects in both TA and healthy groups, but these differences were not significant. In conclusion, the distribution of Dio(2T92A) polymorphism may reflect geographical and ethnic differences, and it is not associated with TA.

When all else fails: stepwise multiple solutions for a complex cancer pain syndrome.

In the presence of insufficient pain relief and substantial adverse effects, application of alternative routes of administration and a change of opioid are the main methods used to improve the analgesic response. When all else fails, the result may further be optimized using adjuvant drugs by an alternative route, namely the intrathecal route. A stepwise approach with multiple drugs and routes of administration is described. This was implemented to resolve a complex pain syndrome otherwise considered uncontrollable. We found it possible to manage a very difficult pain situation by intrathecal home infusion through the efforts of a well-trained family and GP and a continuous exchange of information and advice with the pain relief team about changes in therapy to adapt to the clinical situation. A stepwise and a meaningful approach to clinical problems with use of advanced techniques and alternative drugs in the patient's home may be helpful in the treatment of conditions otherwise considered intractable.

Ondansetron in nausea and vomiting induced by spinal morphine.

Nausea and vomiting induced by opioids are relatively frequent in advanced cancer patients, although other factors may play a role. These effects, which tend to disappear after repeated dosing, can usually be controlled with antiemetic drugs, including metoclopramide, haloperidol, and phenothiazines. Occasionally, nausea and vomiting persist, in spite of the prolonged administration of the antiemetic treatment. We report a patient who had nausea and vomiting that was resistant to common antiemetic treatments, change in opioid drugs, and change in route of administration, and who had a complete and immediate response to parenteral or oral ondansetron.

Opioid-sparing effect of diclofenac in cancer pain.

This study investigated the opioid-sparing effect of diclofenac using patient-controlled analgesia with oral methadone. Fifteen patients with advanced cancer participated. After achieving adequate analgesia with regular dosing of oral methadone (T1), patient-controlled analgesia with methadone was administered for 3 days (T2). Intramuscular diclofenac 75 mg twice daily was then added to this regimen for 3 days (T3). Compared to T2 values, methadone dose was significantly reduced at T2 and T2, and pain report (recorded on a visual analogue scale) was significantly reduced at T3. A reduction in methadone plasma concentration was also observed at T2 and T3, although it did not attain statistical significance. Significant decreases in the intensity of several symptoms other than pain were also found at T2 and T3. Diclofenac appears to have a relevant opioid-sparing effect when using patient-controlled analgesia with oral methadone.

Treatment of pain in chronic bowel subobstruction with self-administration of methadone.

Chronic treatment with opioids in cancer patients with chronic intestinal obstruction is hazardous, as uncontrolled constipation may result in definitive bowel obstruction. Intermittent use of opioids adjusted for fluctuating pain levels may enable patients to take the lowest opioid doses that will have sufficient effect, with a consequently lower risk of intestinal side effects. Methadone has many pharmacokinetic characteristics that fit it for use in this clinical situation. In two patients with recurrent episodes of bowel obstruction, methadone used at low doses and at flexible intervals regulated by the patients according to their pain level avoided the occurrence of new episodes of intestinal obstruction. Oral patient-controlled analgesia with methadone may be a simple, safe and cheap method of treating patients with pain associated with subtotal intestinal obstruction.

Subcutaneous fentanyl infusion in a patient with bowel obstruction and renal failure.

Inoperable bowel obstruction in patients with renal failure is a difficult clinical situation. In the last days of life, an accumulation of morphine metabolites in patients with impaired renal function may cause opioid toxicity, including terminal agitation. The use of an alternative drug may prevent morphine metabolite accumulation in uremic patients. Fentanyl may be an alternative to morphine. It has a large apparent volume of distribution, a short plasma half-life, and extensive biotransformation without active metabolites. A patient with acute renal impairment and bowel obstruction was successfully treated with a subcutaneous continuous infusion of fentanyl (25 micrograms/hr) and boluses of 12.5 micrograms for the last 2 days of life, limiting the worsening of the dramatic clinical picture of bowel obstruction combined with renal impairment. No local toxicity was evidenced.

Patient-controlled analgesia with oral methadone in cancer pain: preliminary report.

BACKGROUND: Methadone is a very useful drug in cancer pain because of its low cost, lack of active metabolites, high oral availability, and the rapid onset of its analgesic effect. It seems to be well tolerated in patients with difficult pain syndromes who are receiving high doses of opioids, and it may deter the development of tolerance, but a high individual variation in terminal elimination half-life can result in different rates and extents of drug accumulation. For this reason, oral patient-controlled analgesia with methadone was used in 24 advanced-disease patients with pain. PATIENTS AND METHODS: A regimen of self-administered oral methadone at fixed doses and flexible patient-controlled dosage intervals to achieve adequate analgesia, while avoiding toxic effects of methadone accumulation, was used in 24 patients requiring opioid therapy. After a priming period of three days with fixed doses of 3-5 mg three times a day for naïve patients and 50% of the morphine equivalent of methadone in patients switched from morphine, patients and relatives were instructed to maintain the night-time dose and to administer a second dose when the pain recurred. When more than four doses of methadone a day were used, an increase of the dosage was prescribed. Continuous pain assessment and monitoring of symptoms were offered. RESULTS: The majority of patients achieved good pain relief until death, and three were switched to very low doses of subcutaneous morphine in their final days. The methadone escalation index was about 2% a day, with a mean dosage increase of 0.3 mg a day for an average of 60 days of treatment at doses ranging from 9 to 80 mg. The plasma concentration in 14 patients ranged from 0.013 to 0.273 mcg/ml with dosages of 20-80 mg during chronic treatment. A mean of 2.4 doses a day was reported, including the fixed night-time dose. The extent of side effects was considered acceptable. CONCLUSION: Patient-administered analgesia with oral methadone appears to be a simple, cheap and relatively safe technique for controlling cancer pain, permitting individualization by the patient him- or herself and avoiding the risk of accumulation. Continuous assessment is necessary.

Long-term ketamine subcutaneous continuous infusion in neuropathic cancer pain.

Neuropathic cancer pain may be less responsive to opioids than other pain. Several studies suggest that N-methyl-D-aspartate (NMDA)-receptor antagonists could play a role in the treatment of neuropathic pain. Ketamine is an NMDA-receptor antagonist that is used as an anesthetic and has been suggested as a useful drug for neuropathic pain. Subanesthetic doses of ketamine can yield analgesia without hypnosis. We describe a patient who developed neuropathic cancer pain unresponsive to opioid escalation and spinal administration of a combination of bupivacaine-morphine and was subsequently treated by subcutaneous continuous ketamine infusion. A starting dose of 150 mg/day provided good pain relief and a dramatic reduction of the oral morphine dose (from 5 g to 200 mg). A slow and progressive increase of ketamine and morphine dosage (400 mg and 200 mg by the subcutaneous route, respectively) continued to provide adequate pain relief after 13 months of therapy despite signs of progressive disease.

Suprascapular nerve block by catheter for breakthrough shoulder cancer pain.

BACKGROUND AND OBJECTIVES: Incidental shoulder pain due to movement renders pain control difficult because it requires high basal dosages or additional doses of opioids. Shoulder pain can be alleviated by suprascapular nerve block, and the placement of a catheter can permit the injection of local anesthesia as needed. METHODS: In a patient with lung cancer and continuous chest pain well controlled by opioids but with shoulder breakthrough pain necessitating extra doses of opioids, a suprascapular nerve block was performed via an indwelling catheter. RESULTS: The breakthrough events due to scapular involvement were treated with local injections of 5 mL bupivacaine 0.5% until death (4 weeks later) without any complications. CONCLUSIONS: Continuous suprascapular nerve block is safe and simple and has proven to be useful in avoiding extra doses of opioids.

Effect of clonidine on postpartum shivering after epidural analgesia: a randomized, controlled, double-blind study.

In obstetric patients treated with epidural analgesia during labor and delivery, shivering is quite frequent due to stress, vasodilatation, infusion of fluids, low ambient temperature, and the direct effect of solution injected into the epidural space. Sixty obstetric patients who developed shivering after receiving epidural analgesia for delivery were randomly assigned to treatment with clonidine 0.150 mg i.v. (N = 20), meperidine 50 mg i.v. (N = 20), or saline solution (N = 20). Drug administration was double blind. The effect on shivering (graded as all or none), drowsiness, heart rate, and systolic arterial pressure was evaluated 5 min after the study drug was administered. Clonidine was as effective as meperidine in controlling shivering and caused a greater reduction in heart rate. Drowsiness occurred after clonidine as well as meperidine. Thus, clonidine proved to be effective in controlling shivering and adrenergic response after delivery using epidural analgesia and produced an acceptable level of drowsiness.

[In vitro and in vivo effects of propofol on the hemoglobin dissociation curve]. / Effets du propofol sur la courbe de dissociation de l'oxyhémoglobine in vivo et in vitro.

This study assessed in vivo and in vitro the effects of propofol on the affinity of hemoglobin for oxygen in seven ASA 1 adults. For the in vivo study, venous blood samples were withdrawn before and after premedication, after the injection of 2.5 mg.kg-1 of propofol and after 15 minutes of maintenance at an infusion rate of 0.2 mg.kg-1.min-1. For the in vitro study, propofol was added to the blood withdrawn before premedication in order to obtain two samples at a concentration of 1 microgram.mL-1 and 2 micrograms.mL-1 respectively. Propofol changed neither in vivo, nor in vitro, the P50 and the number of Hill indicating the angle of the slope of the dissociation curve, nor in vivo the concentration of 2,3-DPG.

Long-term follow-up evaluation in HCV chronic hepatitis treated with alpha-2b interferon. A comparison of two protocols.

In a long-term study (27 months) of patients affected by C-virus active hepatitis we have evaluated the effect of decreasing the dose of interferon by 50% and by 75% with respect to the initial efficacious dose (6 MU tiw). Sixty patients received recombinant interferon alpha-2b(r-IFN- alpha-2b) 6 MU tiw for two months followed by 3 MU for seven months (Group A), and 60 patients received r-IFN alpha-2b 6 MU tiw for two months followed by 1.5 MU for seven months (Group B). Three patients in group B failed to return to follow-up and were not considered in subsequent evaluations. Side effects such as to cause suspension of treatment occurred only during the first two months of the study at 6 MU of interferon (3 patients in group A and 6 in group B). During the two months at 6 MU, transaminase values returned to normal in 94 patients (80%). At the end of follow-up, 49 of these patients (42% of the 117 patients examined; or 48.3% in group A and 35.1% in group B) had normal transaminase levels. In no case did the anti-HCV test become negative. On a reduced dose of interferon, relapses occurred more frequently in group B (21.4%) than in group A (9.6%), but the difference was not significant. No difference between responders and non-responders, including relapsing patients, was observed in relation to gender, age, presence of cirrhosis, presence of B-virus antibodies and initial levels of serum transaminase.

Gastric endoscopic features in patients with liver cirrhosis: correlation with esophageal varices, intra-variceal pressure, and liver dysfunction.

This study was aimed at evaluating the gastric endoscopic features in patients with liver cirrhosis and at assessing whether endoscopic findings correlated with the severity of portal hypertension and of the underlying liver disease. We studied 394 cirrhotic patients and 110 controls. Prevalence of a mosaic-like pattern of the gastric mucosa was significantly higher in cirrhotics than controls (80.5 vs. 0.9%; p < 0.001). Red spots of the gastric mucosa were found in 8.1% of cirrhotic patients and in none of the control subjects. Erosions and petechiae were found in 14.5 and 5.4% of the control population, but their prevalence was significantly higher in cirrhotics (28.7 and 12.7%, respectively; p < 0.05). Severity of the mosaic-like pattern as well as the presence of red spots were closely related to the size and hemorrhagic risk of esophageal varices and to the presence of fundic varices. Also, severe mosaic-like patterns were found more frequently in patients with severe impairment of liver function, as assessed by the Child-Pugh's criteria. Furthermore, the mosaic-like pattern was more severe in cirrhotic patients with a higher degree of portal hypertension as indirectly assessed by measurement of esophageal intravariceal pressure. In conclusion, (1) a mosaic-like pattern and red spots of the gastric mucosa are the only specific signs of congestive gastropathy in liver cirrhosis, and (2) the severity of the mosaic-like pattern correlates with the severity of liver dysfunction and of portal hypertension.

Regional variations in total and nonprotein sulfhydryl compounds in the human gastric mucosa and effects of ethanol.

This study evaluated the regional distribution of sulfhydryl compounds in the human gastric mucosa and the effect of ethanol on gastric sulfhydryl tissue levels. Total sulfhydryl, glutathione, and cysteine and their oxidized forms were measured in biopsy specimens taken from the gastric body and antrum of 22 healthy volunteers. Total sulfhydryl and glutathione contents of the body of the stomach were significantly higher than those of the antrum. In contrast, cysteine concentration was higher in the gastric antrum than in the body. No difference was found in the levels of oxidized sulfhydryls between the gastric body and antrum. The effect of acute administration of ethanol on gastric sulfhydryl content was studied in nine subjects. Ethanol caused gross mucosal damage and lowered the concentration of sulfhydryl compounds in both the body and the antrum. In 10 chronic alcoholics total sulfhydryl and glutathione, but not cysteine, were markedly decreased in the gastric body but not in the antrum as compared with nonalcoholic controls. In conclusion, 1) the human gastric body contains significantly higher tissue levels of total sulfhydryls and glutathione and lower concentrations of cysteine than the antrum; 2) ethanol in a damaging concentration significantly decreases gastric tissue levels of sulfhydryl compounds; and 3) chronic ethanol intake lowers total sulfhydryl and glutathione tissue levels in the gastric body.

[Importance of an outpatient record in obstetric anesthesia]. / Importanza dell'ambulatorio di anestesia ostetrica.

A computerised record was used to collect data following an anesthesiological check-up of pregnant women at approximately 30 weeks of pregnancy. The record was input onto a portable PC in the anesthesia outpatient clinic, memorized on disk (3.5") and then transferred onto a PC network (one PC for each operating theatre) for "real time" consultation of each patient's data. All pregnant women attending the antenatal clinico were also given a folder illustrating epidural anesthetic techniques. Seven hundred and nine outpatient visits have been performed over the past two years with a 62% utilisation ratio. The collection of data using a computerised system allows a rapid and efficacious system of communication to be set up among the membranes of the anesthesiological team, thus encouraging the use of epidural techniques during labour. The distribution of the folder also facilitated the task of the anesthetist who found that pregnant women visiting the anesthesia clinic were already familiar with the epidural technique.

[Continuous infusion peridural analgesia in labor]. / Analgesia peridurale per infusione continua nel travaglio di parto.

A technique of continuous infusion epidural anesthesia was used during labour in 933 patients divided into three groups according to age: Group A (14-18 years old), Group B (19-35 years old) and Group C (greater than 35 years old). Infusion was carried out using the following system: a PVC pressurized bag containing 0.3% marcain connected to 2 flow regulators which ensured a flow of 6 ml/h. During the dilatation phase, 85% of patients received sufficient analgesia, whereas 15% required extra boluses. During the expulsive phase 80% of patients received adequate analgesia of the perineal plane, 12% received an extra bolus of marcain 0.3% and local anesthesia was performed in 8% to allow infiltration. Instruments were required in 5.6% of patients in Group A, 11.3% in Group B and 7.4% in Group C. The incidence of Caesarian section was 5.6% in Group A, 9% in Group B and 14.8% in Group C. No maternal complication was observed. Epidural anesthesia via continuous infusion was therefore shown to be an efficacious and safe method for ensuring analgesia during labour.

[Evaluation of the liberation of urinary necrosis enzymes (NAG-AAP) after administration of plasma expanders: study of dextran 40, hydroxyethyl starch and polymerized gelatin]. / Valutazione della liberazione degli enzimi urinari di necrosi (NAG-AAP) dopo somministrazione di plasmaexpanders: studio su destrano 40, amido-idrossietilico e gelatina polimerizzata.

We studied the 24-hour urinary elimination of enzymatic markers of renal tubular necrosis (NAG-AAP) in 21 patients (mean age 34.6 years old) who were treated with plasma expanders before peridural anesthesia. The patients were divided into three groups of seven subjects each: - 14 ml/Kg -1 of dextran 40 was administered to group 1 - 14 ml/Kg -1 of gelatin was administered to group 2 - 14 ml/Kg -1 of hydroxyethyl starch was administered to group 3. Urinary elimination of N-acetylglucosaminidase and of alanine aminopeptidase was determined in the 24-hour urine the day before surgery (controls), the day of surgery (G1) and the day after surgery (G2). The values of the samples, taken after plasma expander administration, did differ significantly from the control values (G1, G2). Therefore the administration of 14 ml/Kg -1 of dextran, gelatin or hydroxyethyl starch does not affect the renal tubular epithelium.

Prevalence of HBcAg and delta-Ag in liver tissue of patients with HBsAg positive chronic hepatitis.

One hundred and twenty HBsAg positive patients with chronic liver disease, 94 with CAH and 26 with CPH, were studied in order to characterize chronic HBsAg positive hepatitis virologically. All patients came from a geographical area (Campania, Italy) with a high prevalence of HBV and HDV infection. Each patient was tested for the presence of HBsAg, HBeAg, anti-HBe and anti-delta in serum (by RIA techniques), and of HDV (by direct immunofluorescence) and HBcAg (by indirect immunofluorescence and PAP-immunoperoxidase) in liver biopsy specimens. Anti-delta serum positivity was remarkably more frequent in patients with CAH (40%) than in those with CPH (19%). Delta-Ag was found in 94.7% of the anti-delta positive patients with CAH, but in none of the five anti-delta positive patients with CPH. In contrast, the frequency of HBcAg tissue positivity was similar in CAH and CPH. Positivity for HBcAg was less frequent in CAH with cirrhosis than in CAH without cirrhosis, while there was no difference in the prevalence of delta-Ag.