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.     

Frequent loss of expression of the cyclin-dependent kinase inhibitor p27(Kip1) in estrogen-related Endometrial adenocarcinomas.

PURPOSE: p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P 相似文献   

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.     

Everything You Always Wanted to Know about Sarcopenia but Were Afraid to Ask: A Quick Guide for Radiation Oncologists (impAct oF saRcopeniA In raDiotherapy: The AFRAID Project)

Sarcopenia (SP) is a syndrome characterized by age-associated loss of skeletal muscle mass and function. SP worsens both acute and late radiation-induced toxicity, prognosis, and quality of life. Myosteatosis is a pathological infiltration of muscle tissue by adipose tissue which often precedes SP and has a proven correlation with prognosis in cancer patients. Sarcopenic obesity is considered a “hidden form” of SP (due to large fat mass) and is independently related to higher mortality and worse complications after surgery and systemic treatments with worse prognostic impact compared to SP alone. The evaluation of SP is commonly based on CT images at the level of the middle of the third lumbar vertebra. On this scan, all muscle structures are contoured and then the outlined surface area is calculated. Several studies reported a negative impact of SP on overall survival in patients undergoing RT for tumors of the head and neck, esophagus, rectum, pancreas, cervix, and lung. Furthermore, several appetite-reducing side effects of RT, along with more complex radiation-induced mechanisms, can lead to SP through, but not limited to, reduced nutrition. In particular, in pediatric patients, total body irradiation was associated with the onset of SP and other changes in body composition leading to an increased risk of cardiometabolic morbidity in surviving adults. Finally, some preliminary studies showed the possibility of effectively treating SP and preventing the worsening of SP during RT. Future studies should be able to provide information on how to prevent and manage SP before, during, or after RT, in both adult and pediatric patients.     

Characterization of COR627 and COR628, two novel positive allosteric modulators of the GABA(B) receptor

The potential efficacy of GABA(B) receptor agonists in the treatment of pain, drug addiction, epilepsy, cognitive dysfunctions, and anxiety disorders is supported by extensive preclinical and clinical evidence. However, the numerous side effects produced by the GABA(B) receptor agonist baclofen considerably limit the therapeutic use of this compound. The identification of positive allosteric modulators (PAMs) of the GABA(B) receptor may constitute a novel approach in the pharmacological manipulation of the GABA(B) receptor, leading to fewer side effects. The present study reports the identification of two novel compounds, methyl 2-(1-adamantanecarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate (COR627) and methyl 2-(cyclohexanecarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate (COR628), which act as GABA(B) PAMs in 1) rat cortical membranes and 2) in vivo assay. Both compounds potentiated GABA- and baclofen-stimulated guanosine 5'-O-(3-[(35)S]thio)-triphosphate binding to native GABA(B) receptors, while producing no effect when given alone. GABA concentration-response curves in the presence of fixed concentrations of COR627 and COR628 revealed an increase of potency of GABA rather than its maximal efficacy. In radioligand binding experiments [displacement of the GABA(B) receptor antagonist, 3-N-[1-((S)-3,4dichlorophenyl)-ethylaminol]-2-(S)hydroxypropyl cyclo-hexylmethyl phosphinic acid ([(3)H]CGP54626)], both COR627 and COR628 increased the affinity of high- and low-affinity binding sites for GABA, producing no effect when administered alone up to a concentration of 1 mM. In vivo experiments indicated that pretreatment with per se ineffective doses of COR627 and COR628 potentiated the sedative/hypnotic effect of baclofen. In conclusion, COR627 and COR628 may represent two additional tools for use in investigating the roles and functions of positive allosteric modulatory binding sites of the GABA(B) receptor.     

Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study

OBJECTIVES

This study investigated the prognostic value of left ventricular (LV) mass at echocardiography in uncomplicated subjects with essential hypertension.

BACKGROUND

Only a few single-center studies support the prognostic value of LV mass in uncomplicated hypertension.

METHODS

The MAssa Ventricolare sinistra nell’Ipertensione study was a multicenter (45 centers) prospective study. The prespecified aim was to explore the prognostic value of LV mass in hypertension. Admission criteria included essential hypertension, no previous cardiovascular events, and age ≥50. There was central reading of echocardiographic tracings. Treatment was tailored to the single subject.

RESULTS

Overall, 1,033 subjects (396 men) were followed for 0 to 4 years (median, 3 years). Mean age at entry was 60 years, and systolic/diastolic blood pressure was 154/92 mm Hg. The rate of cardiovascular events (×100 patient-years) was 1.3 in the group with normal LV mass and 3.2 in the group (28.5% of total sample) with LV mass ≥125 g/body surface area (p = 0.005). After adjustment for age (p < 0.01), diabetes (p < 0.01), cigarette smoking (p < 0.01) and serum creatinine (p = 0.03), LV hypertrophy was associated with an increased risk of events (RR [relative risk] 2.08; 95% CI [confidence interval]: 1.22 to 3.57). For each 39 g/m² (1 SD) increase in LV mass there was an independent 40% rise in the risk of major cardiovascular events (95% CI: 14 to 72; P = 0.0013).

CONCLUSIONS

Our findings show a strong, continuous and independent relationship of LV mass to subsequent cardiovascular morbidity. This is the first study to extend such demonstration to a large nationwide multicenter sample of uncomplicated subjects with essential hypertension.     

Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis

Objective: The aim of this study was to evaluate the incidence, prognostic factors and clinical significance of delayed clearance of serum HBsAg in compensated cirrhosis B.
Methods: This was a retrospective cohort study of 309 consecutive white patients with biopsy-proved compensated cirrhosis type B.
Results: During a mean follow-up of 68 months, HBsAg loss occurred in 32 patients, including 16 (8%) of 196 untreated patients (mean annual incidence 0.8%), 8 (10%) of 82 interferon (IFN) alpha–treated patients and eight patients who had been treated with other antivirals or steroids. The 5-yr probability of HBsAg loss was 4% and 16% for untreated and IFN-treated patients, respectively (   p = 0.0001  ). Cox's regression analysis identified hepatitis B e antigen–positivity at entry as the sole independent prognostic factor for HBsAg loss. Of the 32 patients who lost HBsAg, one (3%) subsequently developed hepatocellular carcinoma (HCC) and died, whereas, among the patients who remained HBsAg-positive, 11% developed HCC and 20% had died. The probability of HCC appearance was lower (   p = 0.0137  ) and survival was longer (   p = 0.0006  ) in patients who cleared HBsAg compared with patients with HBsAg persistence.
Conclusion: The incidence of HBsAg loss is about 0.8% in cirrhosis type B. Prognostic factors for clearance of HBsAg are initial HBeAg positivity and therapy with alpha interferon. Patients with cirrhosis type B, who lose HBsAg, have a low risk for liver cancer or liver-related death.