A device to select the optimal time to replace the pacemaker activated by a lithium-iodine battery: results of 8 years of experience

The discharge curve of lithium-iodine batteries does not havefeatures which make the clinical decision to replace the pacemakereasy. The output voltage fall corresponding to the end of theirlife is evidenced by variations of the output variables (frequencyand/or length of pulse) and the time of elective replacementtime (ER) is arbitrarily established by the manufacturer, ERmay be too early or too late in relation to the threshold valueof myocardial stimulation. Furthermore, the variables indicatingend of life may be changed by troubles in the circuit components,irrespective of the state of battery. A device to detect theoptimal time for replacement (OR) of pacemaker was studied in1692 subjects with implanted LEM VVl electro-stimulators. Thisdevice consists of a resistance of 110 connected in serieswith the catheter through a magnetic switch, which is activatedby placing a magnet over the skin. The transient connectionof the resistor reduces the output voltage by an amount dependingon the resistive load between the electrodes. In a follow-up of 35 000 months the OR device revealed a verygood reliability. Pacemaker replacement, established when stimulation becomesineffective during the application of the magnet or when thespike amplitude in the standard oscilloscope rapidly declined,was necessary in 77 patients (six of them were excluded dueto a circuit blackout). The OR device was useful in 53 patients(74.6%) with a chronic myocardial threshold of more than 2.5V, useless in 18 patients with a myocardial threshold lowerthan 2.5 V; to obviate this limitation a new OR device is describedfeigning a temporary increment of battery impedance. The employmentof the OR device rather than using ER enabled the patients togain 1333 months of stimulation. The gain of pacing varied froma few months to 3 years, with an average of 18.7 months.     

Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration.

The involvement of adenosine A(1) and A(2A) receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A(1) receptor agonist CPA and the A(2A) receptor agonist CGS 21680 by caffeine, the selective A(1) receptor antagonist CPT, and the A(2A) receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motor-activating effects of acutely administered caffeine in rats involve the central blockade of both A(1) and A(2A) receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true cross-tolerance to CPT. The present results suggest that development of tolerance to the effects of A(1) receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A(2A) receptor blockade.     

Soluble CD30 serum antigen in Kawasaki disease

⁴Very high levels of sCD30, a glycoprotein surface antigen expressed by T lymphocytes and other mononuclear cells of the immune system, were found in serum samples from 10 children with typical Kawasaki disease (KD), but not in blood specimens from a vast cohort of paediatric control subjects. These data strongly support an involvement of CD30+T cells in the immune processes which take place at the level of lymphoid organs during the acute phase of KD.     

Exposure to delta-9-tetrahydrocannabinol (THC) increases subsequent heroin taking but not heroin's reinforcing efficacy: a self-administration study in rats.

One concern about the widespread use of cannabis is that exposure to its active ingredient, delta-9-tetrahydrocannabinol (THC), might increase future reinforcing effects of other abused drugs such as heroin. In this study, we investigated the effects of pre-exposure to THC on subsequent intravenous self-administration of heroin by Sprague-Dawley rats. In one group of rats, we studied (1) acquisition of heroin self-administration behavior using a continuous-reinforcement (fixed-ratio (FR) 1) schedule, (2) heroin dose-response relationships using an FR1/variable-dose schedule, and (3) reinforcing efficacy of heroin using a progressive-ratio schedule. The number of rats pre-exposed to THC that subsequently learned to self-administer 50 microg/kg injections of heroin within 10 daily sessions did not differ from vehicle-pretreated controls. In contrast, rats pre-exposed to THC subsequently self-administered significantly more heroin injections per session and showed significantly shorter post-injection pauses over a range of heroin doses (12.5-100 microg/kg/injection) using the variable-dose schedule. Interestingly, the maximum effort rats would exert to receive an injection of the different doses of heroin under the progressive-ratio schedule was not altered by THC pre-exposure. In a second group of rats, we varied the 'price' of heroin (responses required/dose), by manipulating FR response requirements at different doses of heroin across sessions, to calculate demand and response output curves. Again, consumption was significantly higher in the THC-treated rats at the lowest prices of heroin (FR1/100 microg/kg and FR1/50 microg/kg) but there were no differences in the reinforcing efficacy of heroin between THC- and vehicle-pretreated rats. Altogether, these results demonstrate that pre-exposure to THC alters some pharmacological effects of heroin that determine frequency of heroin taking, but offer no support for the hypothesis that pre-exposure to THC alters heroin's efficacy as a reinforcer.     

Prospective study of the meaning of indeterminate results of the Recombinant Immunoblot Assay for hepatitis C virus in blood donors

Background

The interpretation of “indeterminate” results of the recombinant immunoblot assay (RIBA) is a particularly sensitive issue for Transfusion Services, and donors with such a serological condition require long-term follow-up.

Materials and methods

In the Immunohaematology and Transfusion Medicine Division of Umberto I University Hospital (Rome, Italy), 102,979 donor blood units were screened for hepatitis C virus (HCV) antibodies by enzyme-linked immunosorbent assay (ELISA) over a 5-year period (01.01.2000 – 31.12.2004). Since 24.10.2001, HCV -RNA testing was added. All samples repeatedly reactive by ELISA were then submitted to a HCV confirmatory assay (RIBA).

Results

Among the 102,979 donors we found 271 positive to HCV ELISA testing. The results of the RIBA assay for these donors were negative in 178 (65.7%) cases, positive in 28 (10.3%) and indeterminate in 65 (24.0 %).Of the 65 subjects with an indeterminate pattern, 24 completed a sufficient follow-up (median 25 months; range, 6 – 52), during which some (n=8; 33%) converted to a negative status, some (n=16; 67%) maintained their reactivity pattern, but none became seropositive for HCV.

Conclusions

The HCV-RIBA indeterminate status may indicate either a non-specific reaction (false positive) or a real pre-existing or initial infection and does not, therefore, enable a prediction of outcome. The use of HCV genomic assays (nucleic acid amplification testing), which are more specific than antibody-based assays (ELISA, RIBA), therefore improves HCV blood donor testing by allowing an accurate interpretation of such primary assays.     

Hepatitis C virus genotypes: distribution and clinical significance in patients with cirrhosis type C seen at tertiary referral centres in Europe

The aim of this study was to evaluate the distribution and clinical significance of hepatitis C virus (HCV) genotypes in European patients with compensated cirrhosis due to hepatitis C (Child class A) seen at tertiary referral centres. HCV genotypes were determined by genotype-specific primer PCR in 255 stored serum samples obtained from cirrhotics followed for a median period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, absence of complications of cirrhosis and exclusion of all other potential causes of chronic liver disease. The proportion of patients with types 1b, 2, 3a, 1a, 4 and 5 were 69%, 19%, 6%, 5%, 0.5% and 0.5%, respectively. Kaplan–Meier 5-year risk of hepatocellular carcinoma (HCC) was 6% and 4% for patients infected by type 1b and non-1b, respectively ( P =0.8); the corresponding figures for decompensation were 18% and 7% ( P =0.0009) and for event-free survival were 79% and 89% ( P =0.09), respectively. After adjustment for baseline clinical and serological features, HCV type 1b did not increase the risk for HCC [adjusted relative risk=1.0 (95% confidence interval=0.47–2.34)], whereas it increased the risk for decompensation by a factor of 3 (1.2–7.4) and decreased event-free survival by a factor of 1.7 (0.9–3.10). In conclusion, type 1b and, to a lesser extent, type 2, are the most common HCV genotypes in European patients with cirrhosis. HCV type 1b is not associated with a greater risk for HCC, but increases the risk for decompensation by threefold in patients with cirrhosis.     

Laparoscopic and open gastric resections for malignant lesions: A prospective comparative study

Background Whereas laparoscopy for benign diseases provides clear advantages over traditional surgery, the benefits of laparoscopic gastric resection for malignant diseases are less clear. The objectives of this study were to compare prospectively the clinical outcomes between completely laparoscopic and open total and partial gastrectomies for malignant diseases and to assess whether laparoscopic gastrectomies obtain adequate margins and follow oncologic principles.Methods Between April 1995 and March 2004, a prospective comparative study was performed comparing eight patients who underwent laparoscopic total gastrectomy with 11 patients who underwent open total gastrectomy, and 16 patients who underwent laparoscopic partial gastrectomy with 17 who patients underwent open partial gastrectomy. Stage, extent of lymphadenectomy, and long-term follow-up were examined. The intraoperative and postoperative details of the two groups were compared.Results The laparoscopic group patients had fewer intraoperative complications while the operative time was similar to that of the open group. Both ambulation and hospital stay were significantly shorter in the laparoscopic groups than in the open groups. The short-term morbidity was lower in the laparoscopic groups and there were no cases of death, whereas one case of postoperative death occurred after an open total gastrectomy. There was no need to convert to open surgery. The number of lymph nodes obtained in the laparoscopic and open procedures was not significantly different. In addition, all resected margins were tumor free in the laparoscopic group, whereas tumor involvement was presented in the margin of one specimen in the open group.Conclusions The totally laparoscopic approach to total and partial gastrectomies had good results and was proven to be a feasible and safe procedure. In addition, the laparoscopic procedures are superior to open surgeries in terms of faster postoperative recovery, shorter hospital stay, and better cosmetic outcomes. A totally laparoscopic approach for early and advanced gastric cancer can obtain adequate margins and follow oncologic principles.