Ageing alters intrahypothalamic release patterns of vasopressin and oxytocin in rats

The ageing process has been shown to have a profound impact on the hypothalamo-neurohypophysial system (HNS) and the hypothalamo-pituitary-adrenocortical (HPA) axis in humans as well as in rodents. Therefore, in this study, the intracerebral and peripheral release patterns of both vasopressin and oxytocin have been studied in aged male Wistar rats under basal conditions and in response to ethologically relevant stressors, using intracerebral microdialysis and chronic blood sampling techniques, respectively. Approximately a twofold higher basal release of arginine vasopressin (AVP) within the hypothalamic paraventricular nucleus (PVN), but not within the supraoptic nucleus (SON), was found in aged rats, whereas basal oxytocin (OXT) release did not differ in comparison with young rats. With increasing age the rise in intra-PVN release of both AVP and OXT was blunted in response to forced swimming. In contrast, the intra-SON release of AVP was unrelated to age. Simultaneously recorded basal secretion of both AVP and OXT from the neurohypophysis into blood was increased in aged rats, with a blunted OXT response to swim stress. Opposed to that, plasma AVP levels remained unchanged in both groups. Basal plasma levels of corticotropin (ACTH) and corticosterone were elevated in aged rats, whereas stress-elicited ACTH and corticosterone responses were indistinguishable. These results indicate age-related changes in the HNS and HPA axis with an enhanced basal activity opposed to a blunted response to stressors with increasing age. The increased basal release of AVP within the PVN suggests a role of intracerebral AVP in age-associated alterations of HPA axis regulation.     

Validation of BIOMED-2 multiplex PCR tubes for detection of TCRB gene rearrangements in T-cell malignancies.

The BIOMED-2 Concerted Action BMH4-CT98-3936 on 'Polymerase chain reaction (PCR)-based clonality studies for early diagnosis of lymphoproliferative disorders' developed standardized PCR protocols for detection of immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements, including TCR beta (TCRB). As no comparable TCRB PCR method pre-existed and only a limited number of samples was tested within the BIOMED-2 study, we initiated this study for further validation of the newly developed TCRB PCR approach by comparing PCR data with previously generated Southern blot (SB) data in a series of 66 immature (ALL) and 36 mature T-cell malignancies. In 91% of cases, concordant PCR and SB results were found. Discrepancies consisted of either failure to detect SB-detected TCRB rearrangements by PCR (6.5%) or detection of an additional non-SB defined rearrangement (2.5%). In 99% of cases (99/100), at least one clonal TCRB rearrangement was detected by PCR in the SB-positive cases. A predominance of complete Vbeta-Jbeta rearrangements was seen in TCRalphabeta(+) T-cell malignancies and CD3-negative T-ALL (100 and 90%, respectively), whereas in TCRgammadelta(+) T-ALL, more incomplete Dbeta-Jbeta TCRB rearrangements were detected (73%). Our results underline the reliability of this new TCRB PCR method and its strategic applicability in clonality diagnostics of lymphoproliferative disorders and MRD studies.     

Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial

The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.     

CAD/CAM technology-elaboration of electronic model through optical impression in the fabrication of the dental prostheses by a computer assisted device

In modern CAD/CAM technology of dental prosthetics, the "optical impression" taken by special video cameras deploying 3D-recording of the oral situation (Cerec 1, Cerec 2) initiates the computer-generated production of a digital model. The computer receives and renders the digital data obtained through "optical impression" i.e. data acquisition not as a "negative" of the oral situation but as a "positive" copy of it, namely as a digital model in a virtual environment which can be displayed on the screen and be further used in the fabrication of dental prostheses by means of a computer-assisted device (CAM or CIM).     

A follow-up study of infants ≤ 2000 g birthweight treated in central Queensland

This follow-up study was undertaken in an effort to ascertain the morbidity in the survivors of infants ≤2000 g birthweight cared for in the two Rockhampton intensive care nurseries.

Methodology:

The records of all infants ≤2000 g delivered in or transferred to Rockhampton during the 11 year period 1979 through 1989 inclusive were extracted. Efforts were made to contact and examine all of these children. Those found to be disabled were assessed as being mildly, moderately or severely affected.

Results:

Of the 482 infants of birthweight ≤2000 g treated in the period under review, 393 survived to be discharged from hospital. Eight were known to have died subsequently. Of the remaining 385 children, 288 (74.8%) were able to be contacted and their health status determined. A total of 36 infants were found to have significant disabilities. Twenty-four were mildly affected, five moderately and seven severely affected. Severe disability in infants of ≤1000 g was 16% (3/19).

Conclusions:

The incidence of disability was established in 74.8% of the surviving population, It was not dissimilar to the incidence of disability in similar birthweight groups in some Australian tertiary centres for the years under study. It is emphasized that the follow-up was incomplete and recognized that the survival rates and incidence of disability in survivors has improved in tertiary centres since the time frame of this study.     

Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus leucovorin in the second-line treatment of metastatic breast cancer: Results of a phase II study

Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC).Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m², leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m², weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m² was administered additionally on days 1 and 22, q 50 days.Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting.Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.