BACKGROUND: Telomeres are highly conserved repeats at the ends of chromosomes that maintain chromosome stability and reflect the replicative potential of cells. Telomere length can be determined by Southern blot hybridization or quantitative fluorescence in situ hybridization (Q-FISH). Recently, two flow cytometry-based (Flow) FISH protocols have been published. METHODS: We compared the telomere length measured by Southern blotting and Flow FISH using standard beads to calibrate and quantify the fluorescence intensity. RESULTS: The telomeric fluorescence of cord blood and peripheral blood mononuclear cells was similar to that reported by other studies. There was a linear relationship between the telomeric fluorescence determined by Flow FISH and the telomere fragment size determined by Southern blotting (r = 0.89; P < 0.001). CONCLUSION: It is important to set up a center-specific curve and select appropriate cell lines for reference. This Q-Flow FISH protocol will facilitate the measurement of telomere length and allow more meaningful comparison of data (in standard fluorescence units or fragment size) between institutes.

Adult↗

PubMed2001

Imidazoline-modified benzylimidazolines as h5-HT(1D/1B) serotonergic ligands.

Sumatriptan, a h5-HT1D and h5-HT1B receptor agonist used clinically as a migraine-abortive, produces certain side effects thought to result from its affinity for h5-HT1B receptors. The present investigation extends our work with benzylimidazolines as novel non-tryptamine h5-HT(1D/1B) ligands. The effect of N-methylation, N-benzylation, ring-aromatization, and variation of the imidazoline ring on affinity both at h5-HT1D and h5-HT1B receptors was examined. Several compounds were identified with good affinity and enhanced (i.e., > 100-fold) h5-HT1D versus hS-HT1B selectivity.

Benzyl Compounds↗

PubMed2001

The Hong Kong Bridge Protocol. Immediate loading of mandibular Brånemark fixtures using a fixed provisional prosthesis: preliminary results.

BACKGROUND: The Brånemark System Classic is well documented for its successful and predictable results in dental implant rehabilitation. However, the classic two-stage protocol is associated with problems, such as long treatment time and high treatment cost. To overcome these problems, new developments, including early functional loading protocol and Brånemark System Novum, have been introduced by various groups of researchers. In Hong Kong, a protocol has been developed to immediately load the Brånemark System fixtures with a fixed provisional prosthesis. PURPOSE: The goal of this prospective study was to present the Hong Kong Bridge protocol and report the short-term evaluation of this protocol in a group of patients who had undergone dental implant treatment for their edentulous mandibles. MATERIALS AND METHODS: Twenty-seven consecutive patients being treated at the Hong Kong Osseointegration Implant Centre between June 1998 and December 2000 were included in this study. A total of 123 Brånemark System fixtures were installed and regularly followed up for 3 to 30 months. The prosthesis stability and the marginal bone level were regularly evaluated clinically and radiographically, respectively, after the implant surgery. RESULTS: Fifteen of the 27 patients had been followed up for 1 year or longer. Two patients with eight fixtures were withdrawn from the study. Two of the 115 remaining fixtures failed, resulting in an overall implant survival rate of 98.3%. The mean marginal bone change was reported on 49 fixtures that had passed the 1-year review. The mean marginal bone loss was 0.60 mm (p < .05) after 1 year of functional loading. CONCLUSIONS: To load the mandibular Brånemark System fixtures immediately according to the Hong Kong Bridge protocol was a predictable and simple method with good results during this preliminary study period.

Adult↗

PubMed2001

Immediate provisional for single-tooth implant replacement with Brånemark system: preliminary report.

BACKGROUND: The success of osseointegrated implants ad modum Brånemark for single-tooth restorations is documented. Future developments should aim at improving the benefits to patients by decreasing treatment time, minimizing surgical stages, and maximizing esthetic outcomes. Using knowledge from studies of immediate implant placement, one-stage, immediate loading protocols, the authors developed the immediate provisional. PURPOSE: The purpose of this study was to develop a protocol to provide an immediate solution for restoring a single missing tooth in the esthetic zone. The protocol should be simple, predictable, cost effective, and allow the use of other techniques to improve esthetic outcome. MATERIALS AND METHOD: This prospective clinical study included 24 patients treated from August 1999 to October 2000. Single-tooth implant replacement was done according to immediate provisional protocol. Thirteen of the 24 patients had immediate implant placement after tooth extraction. All implants were placed in the esthetic zone. During surgery, emphasis was placed on obtaining primary stability by achieving bicortical anchorage and maximum insertion torque of at least 40 Ncm. CeraOne (Nobel Biocare) abutments were used, and provisional crowns were fabricated immediately before wound closure. The occlusion was protected by adjacent teeth. RESULTS: Within the follow-up period of between 1 month and 15 months, all fixtures in the 24 patients were stable. Crestal bone loss greater than one thread-width was not detected. The esthetic result was considered satisfactory by all patients. CONCLUSIONS: The implant placement and restoration protocol used in this study showed promising initial results for both the immediate implant and healed extraction site groups. The desirable goals of patient satisfaction, excellent esthetic outcomes, and no increase in treatment cost were achieved in this protocol. Further studies to elucidate the potential of the immediate provisional protocol are justified.

Adolescent↗

PubMed1999

Doctor's assistants--do we need them?

OBJECTIVE: To investigate the potential for the doctor's assistant role within an accident and emergency (A&E) department in relation to consultant workload. METHODS: A time and motion evaluation of the activities of four A&E consultants before and after a doctor's assistant was established as a team member within our department. A review of the literature was undertaken to allow comparisons with the American model of the physician assistant within the emergency department. RESULTS: The initial evaluation indicated that over 20% of the consultant's time could have been saved if an assistant were available to perform a variety of non-medical tasks. The restudy performed once the assistant was in post indicated less time was spent by the doctors in "medical" clerical duties (6.7% v 11.5% time), telephone use (5.6% v 7.7%), and venepuncture/cannula insertion (0.4% v 2.1%), and more time was spent on consultation over cases (15.3% v 11.3%) and supervision of other staff (9.3% v 4.1%). These five areas changed significantly (p = 0.005 by paired t test). CONCLUSIONS: The doctor's assistant may have a role in reprofiling the workload of senior doctors in A&E departments in the UK. They may also have a role in reducing the pressure on junior doctors, though this effect was not evaluated.

Data Collection↗

PubMed1998

Benzylimidazolines as h5-HT1B/1D serotonin receptor ligands: a structure-affinity investigation.

Benzylimidazolines may represent a class of 5-HT1D ligands that has yet to be exploited. On the basis of a previous report that the 2-(substituted-benzyl)imidazoline alpha-adrenergic agonist oxymetazoline (8) binds with high affinity at calf brain 5-HT1D receptors, we explored the structure-affinity relationships of a series of related derivatives. Each of the aromatic substituents was removed and then reinstated in a systematic manner to determine the influence of the individual substituents on binding. It was found that all of the aromatic substituents of 8 act in concert to impart high affinity. However, although the 3-hydroxy group could be removed without significantly reducing affinity for h5-HT1D (i.e., human 5-HT1Dalpha) receptors, this modification reduced h5-HT1B (i.e., human 5-HT1Dbeta) receptor affinity by nearly 50-fold. The 2, 6-dimethyl groups also contribute to binding but seem to play a greater role for h5-HT1B binding than h5-HT1D binding. With the appropriate structural modifications, several compounds were identified that display 20- to >100-fold selectivity for h5-HT1D versus h5-HT1B receptors. Preliminary functional data suggest that these compounds behave as agonists. Given that 5-HT1D agonists are currently being explored for their antimigraine action and that activation of h5-HT1B receptors might be associated with cardiovascular side effects, h5-HT1D-selective agents may offer a new lead for the development of therapeutically efficacious agents.

Adrenergic alpha-Agonists↗

PubMed1998

Presence of GHRH mRNA in human pituitary somatotrophinomas and its relationship to in vitro effect of a GHRH-antagonist on GH secretion and cAMP production.

Several earlier studies have shown that some human pituitary GH-secreting somatotrophinomas are able to synthesise and release hypothalamic GHRH and it has been proposed that a positive autocrine feedback loop involving this tumor-derived GHRH may participate in tumorigenesis. We have used in-vitro cell culture and exploited an antagonist to GHRH, (Ac-Tyr1,D-Arg2)-GHRH (1-29)-amide (GHRH-A), to further investigate whether an autocrine loop involving somatotrophinoma-derived GHRH may exist. In situ hybridization demonstrated presence of GHRH transcripts in 5 of 9 human somatotrophinomas. In culture, GHRH-A failed to inhibit basal release of GH or production of cAMP irrespective of presence or absence of GHRH transcripts. However, GHRH-A was able to completely or partially abolish the stimulatory effects of exogenously added GHRH peptide. Additionally, the average stimulatory effect of exogenous GHRH on in vitro GH secretion by somatotrophinomas possessing GHRH mRNA was identical to that shown by tumors not expressing the GHRH gene. Whilst confirming that many human pituitary somatotrophinomas are able to express the GHRH gene, the failure of GHRH-A to inhibit basal GH secretion argues against the concept of the existence of an autocrine stimulatory loop involving secreted GHRH peptide.

Adenoma↗

PubMed1997

2-(1-Naphthyloxy)ethylamines with enhanced affinity for human 5-HT1D beta (h5-HT1B) serotonin receptors.

Although the beta-adrenergic antagonist propranolol (1) binds at rodent 5-HT1B serotonin receptors, it displays low affinity (Ki > 10,000 nM) for its species homologue 5-HT1D beta (i.e., h5-HT1B) receptors. The structure of propranolol was systematically modified in an attempt to enhance its affinity for the latter population of receptors. Removal of the alkyl hydroxyl group, shortening of the O-alkyl chain from three to two methylene groups, and variation of the terminal amine substituent resulted in compounds, such as N-monomethyl-2-(1-naphthyloxy)-ethylamine (11; Ki = 26 nM), that display significantly higher h5-HT1B affinity than propranolol. Compound 11 was shown to bind equally well at human 5-HT1D alpha (h5-HT1D) receptors (Ki = 34 nM) and was further demonstrated to possess h5-HT1B agonist character in an adenylate cyclase assay. It would appear that such (aryloxy)alkylamines may represent a novel class of 5-HT1D receptor agonists.

Adenylyl Cyclases↗