Effect of Simultaneous Didanosine Administration on Itraconazole Absorption in Healthy Volunteers

Study Objective . To investigate the effect of simultaneously administered didanosine (ddI) on the absorption of a single dose of itraconazole. Design . Randomized, crossover, unblinded single-dose pharmacokinetic study in healthy volunteers. Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15. Setting . A university medical center. Patients . Seven healthy men and women. Six subjects (86%) completed the study; one was removed due to the development of a rash. Interventions . Volunteers received a single 200-mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2-week washout period. Serum samples were obtained frequently for 12 hours after the dose. Measurements and Main Results . Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evaluated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's serum concentration-time curve. A mean ± SD peak serum itraconazole concentration of 0.90 ± 0.30 μg/ml was observed at 3.0 ± 0.7 hours when itraconazole was administered alone, compared with undetectable levels in all patients during therapy with ddI. Conclusions . Simultaneous oral administration of ddI significantly decreases absorption of itraconazole. These drugs should not be administered concurrently.     

Zinc deficiency and hyperprolactinaemia are not reversible causes of sexual dysfunction in uraemia

We selected a group of male dialysis patients complaining of sexual dysfunction in whom penile vascular insufficiency and drug-induced impotence had been excluded. Monitoring of nocturnal penile tumescence was used to confirm organic disturbance. Patients with normal serum prolactin concentrations (n = 18) had significantly lower serum zinc values than normal controls (P less than 0.001) and were entered in a 6-month double-blind study comparing oral zinc acetate with placebo. Patients with elevated prolactin concentrations (n = 8) were entered in a 3-month double-blind crossover study comparing oral pergolide mesylate with placebo. In the zinc study, serum zinc concentrations increased (P less than 0.05) in the zinc-treated but not the placebo-treated group. One of nine patients receiving zinc reported improved sexual function, as did two of nine patients receiving placebo. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations in either treatment group. In the pergolide study, serum prolactin values decreased (P less than 0.01) in the pergolide but not in the placebo treatment period. One patient reported improved sexual function during the pergolide treatment period and two during the placebo period. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations after pergolide. These studies show no benefit of zinc or pergolide compared with placebo in the treatment of uraemic impotence.     

Triquetral-lunate arthritis secondary to synostosis

Until recently the problem of painful, symptomatic arthritis of the wrist secondary to congenitally incomplete separation of carpal bones has been infrequently recognized. Five patients with either excessive stress loading or trauma had eight symptomatic wrists with congenitally incomplete separation of the triquetral-lunate joint. Three of these patients had bilateral symptoms. Six of the wrists had been treated by a limited wrist arthrodesis of the triquetral-lunate joint resulting in asymptomatic wrists and improved range of motion. It appears that patients with this congenital condition poorly tolerate stress loading or trauma secondary to deficient intra-articular cartilage formation resulting in a clinical and anatomic state similar to degenerative arthritis. We suggest a limited wrist arthrodesis as definitive treatment for symptomatic congenitally incomplete separation of the triquetral-lunate joint, with possible application in incomplete separation of the other intercarpal joints.     

Rapid isolation and characterization of 118 novel C2H2-type zinc finger cDNAs expressed in human brain

C2H2-type zinc finger genes comprise one of the largest genefamilies in the human genome. These proteins are involved ingenetic regulation and development and are quite conserved throughoutevolution. The finger domains commonly contain the small linkerpeptide TGEKP between some finger units. Here, we report theisolation of 133 human zinc finger cDNAs, of which 118 are novel.These clones were isolated from human brain cDNA libraries usingoligonucleotide hybridization followed by expressed sequencetag (EST) analysis, sequencing from the conserved linker regionusing degenerate oligonucleotide primers. This directed partialsequencing approach to cDNA isolation and characterization,signature sequencing, combines the speed of EST automatic sequencingwith the focus of specific cDNA family analysis. Signature sequencingminimizes the generation of less informative random EST sequencesand provides a unique relative position for sequence comparison.We also show that there is an even distribution of these RNA5from this brain cDNA library, and that these cDNAs contain N-terminaldomains found in other zinc finger genes. This rapid focusedsequencing approach should be applicable to any family of cDNAscontaining short conserved signature peptide sequences.     

The Fort McMurray demonstration project in social marketing: health- and safety-related behaviour among oil sands workers

This is the first round in a series of surveys conducted inFort McMurray as part of the Fort McMurray Demonstration Projectin social marketing. This component of the survey was intendedto focus on the most prominent group of employed workers inthe community and to compare their patterns of response withthe community as a whole. Respondents to the survey were overwhelminglymale (96%), married (72.9%) and living in households of twoto five persons (87.9%). They were predominantly aged 30–44(55%) and graduates of high school (53.5%). Younger male workers(below age 30) were more likely to have a high school diploma(78.3%) or some additional technical or vocational training(21.7% compared to 12.5% overall) and to be unmarried or separated.Attitudes toward safety-related behaviours were stronger thanfor respondents from the community as a whole. Approximately70–100% of all age groups and both sexes showed strongagreement with attitudes involving child car seats and the unacceptabilityof drinking and driving. These attitudes include strong advocacyof vigorous enforcement of occupational health and safety standards.However, they showed a variability similar to the communityas a whole in behaviour at home compared to work, generallyreporting more consistent use of personal protection on thejob than in their own homes, particularly hearing protection.Even so, they were much less likely to perform stretching andwarm-up exercises prior to exertion than community residentsin general. The potential may exist to transfer the technologyand attitudes from workplace health and safety to communitysafety. One possible strategy to accomplish this is to involveworkers in this industry directly in community initiatives.This strategy may be generalizable to any community in whichthere are major employers who place a heavy emphasis on riskcontrol and occupational health and safety.     

Treatment of Vancomycin-Resistant Enterococci,with a Focus on Quinupristin-Dalfopristin

Enterococci are the second most common cause of hospital-acquired infections, and drug resistance among these organisms is a growing problem. Vancomycin-resistant enterococci (VRE) now account for 7.9% of the nosocomial enterococcal infections. There is no standard therapy for VRE. Although some agents have shown in vitro activity alone or in combination, including ciprofloxacin, doxycycline, novobiocin, teicoplanin, chloramphenicol, and rifampin, treatment options are limited to combinations of drugs with marginal efficacy against the pathogens. Quinupristin-dalfopristin is a new investigational agent with activity against gram-positive cocci, including VRE.     

Initial healing in the dog of submerged versus non‐submerged porous‐coated endosseous dental implants

It has previously been reported that porous‐coated root form endosseous dental implants, became well integrated when used in the traditional 2‐stage surgical approach. In this study, the placement of the implant in a 1‐stage (non‐submerged)technique was to be explored. Implants were placed in the mandibles of dogs, and 2 designs were used differing only in that one (experimental) had a 3mm transgingival extension, permitting it to be exposed lo the oral cavity from the outset. 12 (3 per animal) non‐submerged implants were placed on I side of 4 beagle dogs and 12 control (submerged) implants were placed contralaterally. All implants were allowed to heal for 6 weeks, after which histological preparations were made. 2 of 12 non‐submerged implants were lost due to post‐operative complications: otherwise, all implants healed uneventfully. Histomorphometric analysis revealed bone‐implant contact, as assessed by absolute bone contact (ABC) and contact length fraction (CLF). to be greater for the submerged design, suggesting that bone healing may be delayed with the non‐submerged approach. As well. at this early stage of healing, for both implant designs, ABC and CLF were significantly greater on proximal than on buccal and lingual aspects.