Behavioral naltrexone therapy: an integrated treatment for opiate dependence

Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.     

Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT)

The skin sensitization potential of eight unsaturated and one saturated lipid (bio)chemicals was tested in both the LLNA and the GPMT to address the hypothesis that chemicals with unsaturated carbon–carbon double bonds may result in a higher number of unspecific (false positive) results in the LLNA compared to the GPMT. Seven substances (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene and octinol) gave clear positive results in the LLNA (stimulation index (SI)  3) and thus would require labelling as skin sensitizer. Fumaric acid and succinic acid gave clearly negative results. In the GPMT, besides some sporadic skin reactions, reproducible skin reactions indicating an allergic response were found in a few animals for four test substances. Based on the GPMT results, only undecylenic acid would have to be classified and labelled as a skin sensitizer according to the European Dangerous Substance Directive (67/548/EEC) (results for linoleic acid were inconclusive), while the other seven test substances would not require labelling. Possible mechanisms for unspecific skin cell stimulation and lymph node responses are discussed. In conclusion, the suitability of the LLNA for unsaturated compounds bearing structural similarity to the tested substances should be carefully considered and the GPMT should remain available as an accepted test method for skin sensitization hazard identification.     

Relationship between impaired pulmonary diffusion and cardiopulmonary exercise capacity after heart transplantation

STUDY OBJECTIVES: Diffusion impairment and reduced performance in cardiopulmonary exercise testing (CPX) have been found in patients after heart transplantation. The pathogenesis of these abnormalities is unclear. In particular, the contribution of pulmonary interstitial changes has not yet been verified. DESIGN: We analyzed pulmonary function tests, high-resolution CT (HRCT), echocardiography, left heart catheterization, and CPX in transplanted patients. PATIENTS: Forty long-term survivors were studied at a median of 47 months (range, 12 to 89 months) after heart transplantation. RESULTS: Diffusion was impaired in 40% (transfer factor for carbon monoxide) or 82.5% (carbon monoxide transfer coefficient) of the patients. Diffusion impairment was caused by a decreased diffusing capacity of the alveolar capillary membrane in 89% and/or by a decreased blood volume of the alveolar capillaries in 46% of cases. In five patients (12.5%), CT revealed interstitial lung changes. These patients did not have different values of diffusion capacity. Maximal oxygen uptake and ventilatory efficiency during exercise (minute ventilation/carbon dioxide output slope) were impaired in 92% and 46% of the cases, respectively. CONCLUSIONS: Our data show that the diffusion abnormalities are caused by an impaired diffusion status of the alveolar capillary membrane. Interstitial changes detectable in HRCT were found not to be involved in this process. The reduced performance in CPX in our long-term survivors is caused by pulmonary perfusion abnormalities and low tidal volume, which is due to the deconditioning of respiratory muscle, rather than by interstitial changes or diffusion abnormalities.     

CrossLaps and beta-glucuronidase in peri-implant and gingival crevicular fluid

Collagen degradation products of the carboxyterminal region possibly reflect bone and attachment loss. In the present study, the Serum CrossLaps One-Step enzyme-linked immunosorbent assay was used to determine a specific part of the carboxyterminal region of type I collagen, the CrossLaps. Samples of peri-implant and gingival crevicular fluid of 111 implants and 53 teeth from 47 partially or completely edentulous patients were examined in reference to levels of CrossLaps and beta-glucuronidase (beta G), an established marker of periodontal disease. Clinical probing pocket depth (PPD), bleeding on probing (BOP), plaque accumulation, mobility, radiographic bone loss, and the occurrence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia were assessed. The mean values were: for PPD at implants 3.76 +/- 1.41 mm, at teeth 3.44 +/- 0.88 mm; for beta G at implants 0.364 +/- 0.392 pU/min, at teeth 0.314 +/- 0.209 pU/min; for CrossLaps at implants 0.069 +/- 0.059 pmol/min, at teeth 0.082 +/- 0.053 pmol/min. Bleeding on probing was significantly higher on implants than on teeth (McNemar test, P = .004). No significant difference of beta G levels was found between teeth and implants (Wilcoxon test). A negative correlation was found between beta G levels and CrossLaps levels at teeth (Pearson-rank correlation, P = .002). On implants, no significant correlation of these 2 parameters was seen, but significant correlations were found between sulcus fluid flow rate and PPD (P = .012), beta G levels and bone loss (P < 0.0005), and CrossLaps levels and PPD (P = .011). CrossLaps can be detected in both gingival and peri-implant crevicular fluid. While rising levels of beta G may indicate acute peri-implantitis, CrossLaps may not, but could play a role as a marker of ongoing attachment loss.     

Differences of two Borrelia burgdorferi strains in complement activation and serum resistance.

Complement activation and serum resistance of the Borrelia burgdorferi strains B31 (American strain) and PKo (European strain) were compared. In 25% (v/v) normal human serum (NHS) free of B. burgdorferi-specific antibodies the cells of the PKo strain were high activators of complement as indicated by rapid and strong C9 consumption, by deposition of up to 336763 C9 molecules per cell and by the formation of the terminal complement complex on the cell surface. By comparison, complement activation by the B31 strain was low with 5.4-fold less C9 deposited per cell. The addition of B. burgdorferi-specific antibodies to NHS either as purified IgG or heat-inactivated patient sera, had no influence on the results with both strains. After an incubation period of 2h at 37 degrees C in 25% (v/v) NHS most cells of the PKo strain had lost their viability as indicated by cell immobilization and failure to multiply in subcultures. In addition, extensive cell fragmentation and bleb formation were observed in the electron microscope. In contrast, the B31 strain remained alive and morphologically intact after the same incubation with NHS. We conclude from our results that complement activation and serum resistance are properties which differ considerably between isolated strains of B. burgdorferi.     

Molecular mechanisms of gamete recognition and fusion at fertilization

Advances in many areas of reproductive technology have been rapid and, in many respects, have outstripped our knowledge of the fundamental processes of human and animal sperm-egg interactions at fertilization. This is particularly true of human fertilization, where the availability of eggs for research purposes is severely restricted. As a consequence of this, most of the significant advances in our understanding of mammalian fertilization have resulted from studies on animals, particularly the mouse. This review summarizes our current knowledge of the molecular aspects of mammalian fertilization from the point of view of the fertilizing spermatozoon. Particular reference is made to those advances in our knowledge of human fertilization mechanisms. Further understanding of the molecular basis of human fertilization is of paramount importance for the development of new methods of contraception and also for the rational diagnosis and treatment of certain forms of infertility.      

Short-term cardiovascular effects of somatostatin in patients with cirrhosis

Abstract: Somatostatin is used to treat variceal hemorrhage in patients with cirrhosis and portal hypertension. Its systemic hemodynamic effects, however, are not yet well defined. Since cardiomyopathy or pulmonary artery hypertension may occur in patients with cirrhosis, definition of the systemic hemodynamic effects of somatostatin or its analogue octreotide is of clinical importance. The aim of this study was to evaluate the effects of somatostatin, at different doses and under different conditions of administration, on the systemic hemodynamics in 17 patients with cirrhosis. Two sets of experiments were performed. In the first, eight patients received two different bolus doses (100 and 250 μg) of somatostatin. The second set of experiments was designed to study the hemodynamic effects of the combination of a bolus and an infusion of somatostatin. Nine other patients received one bolus of 250 μg of somatostatin, followed by a 250 μg/h infusion for 65 min. A second bolus of 250 μg of somatostatin was injected in these patients after 35 min of infusion. Before and for 30 min after each bolus, systemic hemodynamics were measured. Following a bolus of somatostatin, a dose-dependent decrease in heart rate (from 77±3 to 73±5 beats/min with 100 μg, and from 78±4 to 68±5 beats/min with 250 μg, p<0.05) and increases in systemic and pulmonary artery pressures were observed. The combination of an infusion and a bolus of somatostatin significantly reduced the increases in systemic and pulmonary artery pressures. These results suggest that a combination of an infusion and a bolus of somatostatin might have less deleterious effects on systemic hemodynamics than a bolus alone.     

Glucocorticoid safety for treating rheumatoid arthritis

Introduction: Glucocorticoids (GCs) are often used in the treatment of rheumatoid arthritis and many other inflammatory diseases. Besides strong favorable effects on disease activity, GCs can cause (serious) side effects as well.

Areas covered: Side effects of GCs that are ranked as most important by rheumatologists as well as by patients are bone loss and fractures, cardiovascular events, hypertension, and diabetes mellitus. In evaluating these side effects, confounding by indication is a disturbing factor: not only the use of GCs can increase the risk of several side effects, but so can the activity of the underlying disease, which in turn is related to the amount of GCs that is prescribed to the patient.

Expert opinion: Generally, side effects predominantly occur in patients with a high disease activity and when used in high doses and for a long period of time. For these patients, caution and monitoring are most warranted. However, monitoring is not only recommended in patients with a high disease activity, and high-dose or long-term use of GCs, but in all GC users, since side effects may also occur in patients treated with low-dose GCs. When detecting possible negative effects in time, they might be managed and serious damage due to side effects might hopefully be prevented.