Buprenorphine/naloxone versus methadone in opioid dependence: a longitudinal survey.

BACKGROUND AND OBJECTIVES: Buprenorphine and methadone are widely used for the treatment of opioid dependence, but their diversion and/or misuse are frequent. In principle, buprenorphine/naloxone combination therapy should be associated with a lower frequency of drug abuse/misuse than methadone. This study assessed the efficacy of the substitution of buprenorphine treatment with the buprenorphine/naloxone combination in opioid-dependent patients. MATERIAL AND METHODS: 3812 drug-addicted outpatients selected from 10 Italian Public Services for Addiction (Ser.T.) centres in Naples (Italy) were enrolled: 3105 (81.5%) were treated with methadone and 707 (18.5%) with buprenorphine. The buprenorphine treatment was switched to buprenorphine/naloxone (4:1), and the patients were followed for about 1 year. The number of subjects still on treatment after 1 year, their status according to social, educational and toxicologic (assessed by a urine toxicology test) parameters were assessed. RESULTS: 1 year after the therapy switch, the number of patients still on treatment was similarly reduced with methadone (2883; -7.5%) and buprenorphine/naloxone (632; -10.6%; p=0.369). However, in patients treated with buprenorphine/naloxone, a significant improvement was reported in social life status (63% versus 39% of the buprenorphine/naloxone and methadone treated subjects, respectively, were married/cohabiting p<0.001), in the educational level (43% of buprenorphine/naloxone treated versus 32% of the methadone treated subjects obtained at least a high school certificate, p<0.001) and in the toxicological conditions (53% of buprenorphine/naloxone treated subject versus 30% of methadone treated individuals had opioid- and cocaine- negative urine tests, p<0.001). DISCUSSION: These preliminary data suggest that buprenorphine/naloxone treatment of opioid dependence reduces the percentage of treated subjects similarly to methadone, and is associated with an improvement in social life, educational and toxicological conditions, compared with methadone treatment. However, we cannot exclude a selection bias, i.e. patients who were more likely to stabilize their opiate dependence switched to buprenorphine/naloxone.

Diurnal changes in gas exchange and carbon partitioning in needles of fast- and slow-growing families of loblolly pine (Pinus taeda).

We investigated diurnal and seasonal changes in carbon acquisition and partitioning of recently assimilated carbon in fast- and slow-growing families of loblolly pine (Pinus taeda L.) to determine whether fast-growing families exhibited greater carbon gain at the leaf level. Since planting on a xeric infertile site in Scotland County, NC, USA in 1993, five Atlantic Coastal Plain (ACP) and five "Lost Pines" Texas (TX) families have been grown with either optimal nutrition or without fertilization (control). In 1998 and 1999, gas exchange parameters were monitored bimonthly in four families and needles were analyzed bimonthly for starch and soluble sugar concentrations. Although diurnal and seasonal effects on net photosynthesis (A(net)) and maximum rate of light-saturated photosynthesis (A(max)) were significant, few family or treatment differences in gas exchange characteristics were observed. The A(net) peaked at different times during the day over the season, and A(max) was generally highest in May. Instantaneous water-use efficiency (WUE(i)), derived from gas exchange parameters, did not differ among families, whereas foliage stable isotope composition (delta(13)C) values suggested that TX families exhibited lower WUE than more mesic ACP families. Although there were no diurnal effects on foliar starch concentrations, needles exhibited pronounced seasonal changes in absolute concentrations of total nonstructural carbohydrates (TNC), starch and soluble sugars, and in partitioning of TNC to starch and sugars, mirroring seasonal changes in photosynthesis and shoot and root growth. In all families, foliar starch concentrations peaked in May and decreased to a minimum in winter, whereas reducing sugar concentrations were highest in winter. Some family and treatment differences in partitioning of recently assimilated carbon in needles were observed, with the two TX families exhibiting higher concentrations of TNC and starch and enhanced starch partitioning compared with the ACP families. We conclude that growth differences among the four families are not a function of differences in carbon acquisition or partitioning at the leaf level.

First confirmed case of Neospora caninum-associated abortion outbreak in Portugal.

In a dairy herd experiencing an abortion outbreak, 49% of the 119 cows were positive for Neospora caninum antibodies and the remaining 51% were seronegative. Using immunohistochemical analysis of foetal brain tissue, Neospora cysts and bradyzoite clusters were identified in two of the 15 aborted foetuses submitted for testing. Other agents that commonly cause abortions were not found. These results, coupled with neurological clinical symptoms in new-born calves, implicated N. caninum as the major cause of abortions in this dairy herd. This is the first report that associates N. caninum infection with bovine abortions in Portugal.

Differential diagnosis between hepatocellular carcinoma and cirrhosis through a discriminant function based on results for serum analytes.

We applied a multivariate analysis to a large series of serum biochemical tests in an attempt to identify a function that could efficiently discriminate cirrhosis from hepatocellular carcinoma (HC). We analyzed two successive temporal cohorts (1987-90; 1991-94) of HC and cirrhotic patients, all histologically classified (first cohort: 69 cirrhosis and 39 HC; second cohort: 66 cirrhosis and 38 HC). Using data from the first temporal cohort of patients, we obtained a discriminant function based on seven serum analytes: alpha-fetoprotein, the hepatic isoenzyme of alkaline phosphatase, lactate dehydrogenase isoenzyme 5, total gamma-glutamyltransferase (GGT), GGT isoforms complexed with low-density lipoprotein, aspartate aminotransferase, and copper. The same panel of analytes emerged when the second cohort was tested and also when both cohorts were tested together. In the two successive cohorts (total, 212 patients) with a prevalence of cirrhosis vs HC of approximately 2:1, the discriminant function correctly classified 93% of cases, the highest percentage of correct classification of the two diseases obtained so far by laboratory approaches. Validation with the jackknife reallocation statistical algorithm confirmed these results. In addition, of six patients with liver cirrhosis for whom we had the opportunity of following up and observing the evolution to HC, five were classified as HC at diagnosis by the multivariate discriminant analysis; i.e., discriminant analysis provided a diagnostic lead time of 6-12 months over histology. This discriminant function, based on easy-to-perform serum biochemical tests, may help solve a fundamental problem of differential diagnosis in the evolution of chronic liver diseases from cirrhosis to HC.

Discriminant function based on serum analytes differentiates hepatocarcinoma from secondary liver neoplasia.

Hepatocellular carcinoma (HC) is often difficult to distinguish from secondary liver neoplasia (SLN) by physical and imaging diagnostic procedures alone. To this aim we have extended and improved a laboratory approach based on a serum lactate dehydrogenase isoenzyme ratio (LD4:LD5) by adding the carcinoembryonic antigen: alpha-fetoprotein ratio, alkaline phosphatase, and serum iron concentrations to obtain a highly efficient discriminant function. In two successive cohorts, for a total of 102 patients, all histologically diagnosed, with a prevalence of HC vs SLN of 3:1, we correctly classified 96% of cases (100% of SLN cases). Subsequent verification with the jackknife reallocation statistical algorithm confirmed these results. In conclusion, this discriminant function based on simple laboratory assays of a few analytes is an important tool in solving a diagnostic dilemma in cases of liver neoplasia.

Total discrimination of peritoneal malignant ascites from cirrhosis- and hepatocarcinoma-associated ascites by assays of ascitic cholesterol and lactate dehydrogenase.

No laboratory test completely distinguishes malignant ascites (MA) from ascites associated with cirrhosis and (or) hepatocellular carcinoma (A/C-HC). Ascitic cytology is highly specific but has a diagnostic sensitivity of only 40-60%. We determined 11 ascitic analytes and cytology in 58 patients with cirrhosis, 15 with hepatocellular carcinoma, and 21 with MA (10 ovarian cancers, 4 mesotheliomas, 6 gastrointestinal neoplasias, 1 leukemia). Ascitic total protein, cholesterol, pseudouridine, and lactate dehydrogenase (LD), and the ascitic:serum ratios of total protein and of LD showed the most significant differences between the two groups of patients. Stepwise multiple linear discriminant analysis (applying the Wilks' lambda criterion) of several variables, corroborated by the "jack-knife" reallocation procedure, showed that the ascitic cholesterol and ascitic LD association correctly identified 100% of MA and A/C-HC; cytology had a diagnostic specificity of 100%, but identified only 48% of MA. This association may represent a primary tool for the discrimination of ascites of unknown origin, particularly in the presence of negative cytology findings.

Carbon and phosphorus partitioning in Pinus serotina seedlings growing under hypoxic and low-phosphorus conditions.

Ten-week-old pond pine (Pinus serotina Michx.) seedlings were grown in solution culture at 5 or 100 microM P and under aerobic or hypoxic solution conditions. After 6 and 10 weeks in the treatments, changes in relative growth rate (RGR), P acquisition and allocation, and carbohydrate partitioning were determined by analyzing tissue for total P, soluble sugars and starch. Six weeks of low-P growth conditions decreased seedling dry weight and the ratio of shoot dry weight to root dry weight (S/R) by 39 and 51%, respectively, in comparison to seedlings from the aerobic, high-P (control) treatment. Mean RGRs of shoots in the low-P treatment were reduced by 33%, whereas root growth was unaffected. After 10 weeks of low-P growth conditions, however, both shoot and root RGRs were significantly reduced, and plants had lower S/R ratios than in any other treatment. Slowed shoot growth was accompanied by starch and nonstructural carbohydrate accumulation in needles, indicating that needle growth was not limited by carbohydrate supply. Six weeks of low-P growth conditions decreased total seedling P by 75%, reflecting a 97% reduction in the net uptake rate (NUR). Shoot NUR as a fraction of seedling NUR was also greatly reduced in the low-P treatment, indicating that low-P growth conditions affected P translocation to the shoot more than P accumulation by roots. In contrast, 6 weeks of hypoxic growth conditions decreased total dry weight of seedlings in the high-P treatment by 41% relative to their aerobic counterparts. Root growth was affected more than shoot growth, however, and S/R ratios increased. After 10 weeks, S/R ratios doubled, primarily because of the reduction in root RGR. Nevertheless, roots of hypoxic seedlings contained a higher percentage of total seedling P than their aerobic counterparts. Net P acquisition per seedling decreased by more than 50% under hypoxic growth conditions, as a result of reductions in both root RGR and seedling NUR. Starch accumulation in shoots of hypoxic seedlings reflected reductions both in root growth and in transport of carbohydrates to nonwoody roots. Carbohydrate availability did not appear to be limiting growth of hypoxic woody roots, which are well-aerated internally, but it may have limited metabolic processes in nonwoody roots of seedlings from the high-P treatment.

Serum lactate dehydrogenase isoenzyme 4/5 ratio discriminates between hepatocarcinoma and secondary liver neoplasia.

Total lactate dehydrogenase (LD; EC 1.1.1.27) and its five isoenzymes were determined in sera from (a) 98 cases of cirrhosis at various stages classified according to Child and Turcotte; (b) 37 cases of hepatocarcinoma (HC) at different stages of the Okuda classification; (c) 17 patients with secondary liver neoplasia (SLN), mainly from an abdominal primary site; and (d) 19 cases of abdominal neoplasia without liver metastasis, in an attempt to contribute to the differential diagnosis between these conditions. LD-4 was enhanced in SLN and LD-5 in HC, thus indicating the LD-4/LD-5 ratio as a potential index with which to differentiate between HC and SLN patients. At a cutoff value of 1.05, 91% of these patients were correctly classified (82% for SLN and 95% for HC). Consequently, this biochemical index appears to be an efficient and rapid indicator to distinguish HC from SLN. On the other hand, the LD isoenzymes are unable to discriminate between HC and cirrhosis or between abdominal neoplasia with and without liver metastases.

Effects of anaerobic growth conditions on phosphorus tissue concentrations and absorption rates of southern pine seedlings.

A non-circulating, continuously flowing solution culture was used to examine the long- and short-term effects of anaerobic growth conditions on phosphorus uptake in 12-week-old seedlings of three pine species. Sand pine (Pinus clausa (Engelm.) Sarg.) and a drought-hardy loblolly pine (P. taeda L.) had the largest reductions in biomass after 8 weeks in anaerobic solution, whereas the more flood-tolerant pond pine (P. serotina Michx.) and wet-site loblolly pine seedlings were least affected. Anaerobic growth conditions reduced P concentrations in the shoot and increased P concentrations in the root. Short-term (32)P-uptake experiments were conducted with intact seedlings to determine absorption rates (influx) of inorganic phosphate (Pi) by aerobically and anaerobically grown pine seedlings. Influx of Pi was weakly correlated with shoot fresh weight, root fresh weight, root P and shoot P per gram fresh weight root, suggesting that internal P levels and biomass influenced Pi absorption. The highest Pi absorption rates were found in anaerobically grown seedlings under anaerobic (32)P-uptake conditions. Of these, sand pine had the highest absorption rate in 50 microM KH(2)PO(4) (0.96 micromol Pi g(-1) FW root h(-1)), and the wet-site loblolly pine exhibited the lowest rate (0.24 micromol Pi g(-1) FW root h(-1)). Aerobically grown seedlings had similar Pi absorption rates that were not significantly affected by O(2) concentration in the (32)P-uptake solution.

Evoked potential maps in learning disabled children.

Some childhood learning disabilities are associated with altered synchrony patterns of brain evoked potentials. Scalp recorded electrical synchrony between selected brain regions was measured in response to visual, auditory and somatosensory stimuli and compared between a group of learning disabled children and a group of normal children. Statistically significant inter-group differences revealed stimulus dependent greater inter-regional EP synchrony in the learning disabled group. These findings support the notion that some childhood learning disabilities reflect, in part, altered connections between selected brain regions.