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Renal effects of amlodipine in normotensive renal transplant recipients. The use of cyclosporin A (CsA) has improved the success of renal transplantation, but is associated with hypertension and significant renal toxicity. Previous reports suggest that calcium channel blockers may be useful in opposing the adverse effects of CsA. We have evaluated the effects of amlodipine (5 mg, once daily for 8 weeks) on renal function in 27 normotensive renal transplant recipients with stable renal function, in a double-blind, placebo-controlled, multicentre, cross over study. Amlodipine significantly reduced serum creatinine concentration relative to placebo (mean±SD: 168±65 vs 177±66 μmol/l; P=0.002) and there was a strong trend towards an increase in effective renal plasma flow on amlodipine relative to placebo (238±92 vs 217±87 ml/min; P=0.055). Glomerular filtration rate and lithium clearance were unaffected. Trough CsA blood concentration was unaffected. Amlodipine was well tolerated, with a low incidence of adverse events, and did not affect blood pressure or heart rate. In conclusion, amlodipine reduced serum creatinine in normotensive renal transplant recipients after only 8 weeks treatment, and was well tolerated in concomitant administration with CsA. [ABSTRACT FROM PUBLISHER]

Complexes of aspartic acid (Asp) cationized with Zn 2+ : Zn(Asp-H) + , Zn(Asp-H) + (ACN) where ACN = acetonitrile, and Zn(Asp-H) + (Asp); as well as with Cd 2+ , CdCl + (Asp), were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light generated from a free electron laser. A series of low-energy conformers for each complex was found using quantum chemical calculations to identify the structures formed experimentally. The main binding motif observed for the heavy-metal complex, CdCl + (Asp)[N,CO,CO s ], is a charge-solvated, tridentate structure, where the metal center binds to the backbone amino group and carbonyl oxygens of the backbone and side-chain carboxylic acids. Likewise, the deprotonated Zn(Asp-H) + (ACN) and Zn(Asp-H) + (Asp) complexes show comparable [N,CO - ,CO s ](ACN) and [N,CO - ,CO s ][N,CO,CO s ] coordinations, respectively. Interestingly, there was only minor spectral evidence for the analogous Zn(Asp-H) + [N,CO - ,CO s ] binding motif, even though this species is predicted to be the lowest-energy conformer. Instead, rearrangement and partial dissociation of the amino acid are observed, as spectral features most consistent with the experimental spectrum are exhibited by a four-coordinate Zn(Asp-NH 4 ) + [CO 2 - ,CO s ](NH 3 ) complex. Analysis of the mechanistic pathway leading from the predicted lowest-energy conformer to the isobaric deaminated complex is explored theoretically. Further, comparison of the current work to that of Zn 2+ and Cd 2+ complexes of asparagine (Asn) allows additional conclusions regarding populated conformers and effects of carboxamide versus carboxylic acid binding to be drawn.

The experimental bond energies of Ni 2+ (H 2 O) x complexes, where x = 4-11, are determined by threshold collision-induced dissociation using a guided ion beam tandem mass spectrometer with an electrospray ionization source. The electrospray ionization source produces a distribution of Ni 2+ (H 2 O) x complexes, where an in-source fragmentation technique is employed to access the x = 4-6 complexes and control the population of excited isomers. The kinetic energy-dependent cross sections are modeled to yield 0 K bond energies for sequential loss of neutral water molecules, which are converted to 298 K binding energies. Analysis of the primary and secondary water losses from the Ni 2+ (H 2 O) x reactant ion complexes, x = 4-11, provide accurate thermochemistry for the hydration energies of Ni 2+ and yield the first experimental values for x = 4 and 5 binding energies. Speculative thermochemistry for excited isomers of the x = 4-6 complexes is also obtained. Quantum chemical calculations explore the relative energies of possible geometries. Theoretical bond energies for ground structures are used for direct comparison with experimental values. Our experimental results agree well with previously calculated and experimentally obtained binding enthalpies as well as with the more extensive quantum chemical calculations performed here.

Complexes of asparagine (Asn) cationized with Zn 2+ and Cd 2+ were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light generated from a free electron laser. Electrospray ionization yielded complexes of deprotonated Asn with Zn 2+ , [Zn(Asn-H)] + , and intact Asn with CdCl + , CdCl + (Asn). Series of low energy conformers for each complex were found using quantum chemical calculations in order to identify the structures formed experimentally. The experimentally obtained spectra were compared to those calculated from optimized structures at the B3LYP/6-311+G(d,p) level for [Zn(Asn-H)] + and the B3LYP/def2-TZVP level with an SDD effective core potential on cadmium for the CdCl + (Asn) system. The main binding motif observed for the CdCl + complex is a charge solvated, tridentate [N, CO, CO s ] structure where the metal binds to the backbone amino group and carbonyl oxygens of the carboxylic acid and side-chain amide groups. The Zn 2+ system deprotonates at the backbone carboxylic acid and prefers a [N, CO - , CO s ] binding motif, where binding was observed at the carboxylate site along with the backbone amino group and side-chain carbonyl groups. In both cases, the theoretically determined lowest-energy conformers explain the experimental [Zn(Asn-H)] + and CdCl + (Asn) spectra well. Additionally, complete mechanistic pathways were found for each of the major dissociation reactions of [Zn(Asn-H)] + (primary loss of CO 2 , followed by the sequential loss of NH 3 ) and CdCl + (Asn) (concomitant loss of NH 3 + CO).

Complexes of glutamine (Gln) cationized with Zn(2+) and Cd(2+) were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light generated from a free-electron laser. Electrospray ionization yielded complexes of deprotonated Gln with Zn(2+), [Zn(Gln-H)](+), and intact Gln with CdCl(+), CdCl(+)(Gln). For each complex, the spectra obtained were compared with those for low-energy conformers found using quantum chemical calculations to identify the structures present experimentally. Calculations were performed at the B3LYP/6-311+G(d,p) level for [Zn(Gln-H)](+) and at the B3LYP/def2-TZVP level with an SDD effective core potential on cadmium for CdCl(+)(Gln). The main binding motif observed for the Cd(2+) complex was a charge-solvated, tridentate [N,CO,COsc] structure in which the metal binds to the backbone amino group and the carbonyl oxygens of the carboxylic acid and side-chain amide groups. The Zn(2+) system similarly preferred a [N,CO(-),COsc] binding motif, where binding was observed at the carboxylate site along with the backbone amino and side-chain carbonyl groups. In both cases, the theoretically determined lowest-energy conformers explain the experimental [Zn(Gln-H)](+) and CdCl(+)(Gln) spectra well.

Renal effects of amlodipine in normotensive renal transplant recipients. The use of cyclosporin A (CsA) has improved the success of renal transplantation, but is associated with hypertension and significant renal toxicity. Previous reports suggest that calcium channel blockers may be useful in opposing the adverse effects of CsA. We have evaluated the effects of amlodipine (5 mg, once daily for 8 weeks) on renal function in 27 normotensive renal transplant recipients with stable renal function, in a double-blind, placebo-controlled, multicentre, cross over study. Amlodipine significantly reduced serum creatinine concentration relative to placebo (mean+/-SD: 168+/-65 vs 177+/-66 micromol/l; P=0.002) and there was a strong trend towards an increase in effective renal plasma flow on amlodipine relative to placebo (238+/-92 vs 217+/-87 ml/min; P=0.055). Glomerular filtration rate and lithium clearance were unaffected. Trough CsA blood concentration was unaffected. Amlodipine was well tolerated, with a low incidence of adverse events, and did not affect blood pressure or heart rate. In conclusion, amlodipine reduced serum creatinine in normotensive renal transplant recipients after only 8 weeks treatment, and was well tolerated in concomitant administration with CsA.

Using the results of an analysis of available scientific evidence and a survey of current practice in Canada, as well as expert opinion, these guidelines attempt to consider current partner notification practice in Canada and recommend an approach to determining practice which is flexible enough to address local circumstances. Priority areas for future research were also identified.

Objective: To describe the range of practice for sexually transmitted disease (STD) contact tracing/partner notification (PN) by public health agencies in Canada., Methods: A two-level mailed survey, using two different questionnaires, was conducted from Aug. 1991 to Feb. 1992, directed to: 1) provincial and territorial epidemiologists/directors of STD control, asking about program organization; and 2) 154 local health units/provincially run PN programs, asking about practice patterns of STD partner notification., Conclusions: In Canada, STD PN by public health agencies is routinely practised in most provinces. PN efforts vary by the STD; less PN effort goes to chlamydia despite a high burden of illness; HIV PN is frequently perceived to be within the responsibility of the physician. For STDs with higher PN effort, the preferred method is provider referral. Targeting is seldom utilized, and there are little available data at a local level monitoring even process measures of effectiveness.

Injection drug users (IDUs) entering treatment programs in Montreal and Toronto were recruited for a study of drug using behaviour and risk of HIV infection. Only those who had injected within 6 months of entering their treatment program were eligible for participation. 183 subjects were recruited in Montreal and 167 in Toronto between November, 1988 and October, 1989. Each participant completed a standardized interviewer-administered questionnaire which focussed on, among other things, drug history and needle sharing behaviour. Approximately three-quarters of respondents in both cities reported sharing needles and syringes within the 6-month period prior to their entry into treatment. Our analysis, which focussed on variables associated with needle sharing revealed that having a sexual partner who injected, trouble obtaining sterile needles and syringes and cocaine injection were significantly and independently associated with needle sharing in a logistic regression model which also controlled for city of recruitment.

Staff from 3 Toronto hospitals were surveyed for knowledge, attitudes and concerns about AIDS. 70% of the 1,366 respondents had direct clinical experience with persons with AIDS. Data were analyzed according to hospital setting and professional group: physicians, nurses, technologists and supervisory staff. No setting difference was observed and although statistically significant differences (at the .001 level) were observed between professional groups, these differences are small and have little practical importance. In general, subjects answered 68% of the knowledge questions correctly. All attitudes and concerns were inversely associated to knowledge (Pearson r range was -.31 to -.20). Multivariate analysis demonstrated that knowledge and concern about contagion are important mediating variables (multiple r = .40) for other attitudes and concerns.

We describe the sexual behaviour reported by 240 seronegative and seropositive homosexual men over a 3-year period. Sexual partners of men with HIV disease were recruited into a prospective study between July 1984 and July 1985 and were monitored every 3 months thereafter. Data on sexual activities were collected through interviewer-administered questionnaires. The cohort experienced a reduction in both the number of sexual partners and the volume of sexual activity. Reductions in the number of partners were early and dramatic. Changes in sexual activities were gradual and consistent in trend. The greatest reduction occurred in high risk activities (receptive and insertive anal intercourse). After 3 years of follow-up, only 10% of the men continue to be exposed to semen through unprotected receptive anal intercourse and 18% through unprotected receptive oral-genital sex. The proportion of men engaging in oral-genital contact and masturbation remained stable over the 3 years. Once informed of their serostatus, both seropositive and seronegative men reduced their high risk behaviour. The decline in rates of STDs and seroconversion confirmed that this cohort had indeed reduced their high risk behaviour.

Testing saliva for the detection of human immunodeficiency virus (HIV) antibodies has many potential advantages for epidemiologic surveillance. A commercial ELISA kit and a standardized in-house immunoblot (IB) system were slightly modified to enhance antibody detection in saliva. Frozen saliva specimens from Toronto Sexual Contact Study participants (including sequential saliva specimens collected during seroconversion) were tested as were fresh saliva samples collected from a population of street-based intravenous drug users (IVDUs). HIV antibody results on saliva were compared with HIV serostatus determined by ELISA and IB on serum or dried blood spots. The overall sensitivity was 98.3% (117/119) for the kit and 99.2% (118/119) for IB; the specificity was 100% (429/429). In the IVDU population, compliance in the voluntary submission of specimens increased from 69% agreeing to provide blood samples to 89% agreeing to provide blood, saliva, or both. Saliva specimens can be easily collected under difficult field conditions with minimal training and provide a valuable alternative to testing blood for HIV-seroprevalence studies.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

To estimate the rate of underreporting of AIDS (acquired immune deficiency syndrome) to the Federal Centre for AIDS (FCA), in 1988 the initials, date of birth and place of residence of 66 patients with AIDS known to the Toronto Sexual Contact Study (TSCS), 65 patients with AIDS known to the Vancouver Lymphadenopathy-AIDS Study (VLAS) and other participants in both studies who did not have AIDS were sent to the Bureau of Epidemiology and Surveillance, FCA. The FCA conducted a manual record linkage to link these data to the national registry of reported cases. The rate of underreporting was 12% (8/65) for the VLAS and 18% (12/66) for the TSCS. The specific diagnosis was not related to the rate of underreporting. For the TSCS the rate of underreporting had increased from 0% in 1983-84 to 44% in 1987-88 (p = 0.001). Differences in the observed rates of underreporting between the two studies are likely the result of differences in the reporting responsibilities of physicians involved in the studies.

Approximately 50 000 individuals are employed in various hospital-based occupations in Metropolitan Toronto. To determine the proportion of this population that might be considered as first-priority recipients of the new hepatitis B vaccine, a questionnaire was sent to the executive directors of 45 hospitals in this region. The questionnaire requested data on the numbers of full- and part-time employees whose frequency of contact with blood and blood-related equipment was the greatest. The response rate was 89%. Of the 9545 individuals identified as being at risk of exposure to hepatitis B, 5443 (57%) were nonphysicians and 4102 (43%) were physicians. A highly significant (p less than 0.001) positive and linear relation was found between the numbers of personnel at highest risk of exposure and the total number of hospital personnel and type of hospital. Therefore, the potential exists for developing and validating a simple bivariate model that could predict the initial vaccine requirements for hospital-based personnel in Ontario and other provinces.

As the AIDS epidemic spreads, many patients are asking their primary-care physicians to perform AIDS (HIV-antibody) testing, and in some settings, clinical circumstances prompt physicians to consider ordering the test. As a result, thousands of HIV-antibody tests are being requested each month by Canadian family doctors, where none were available only two years ago. Yet particular characteristics of HIV infection make these tests very unlike most blood tests, since their use carries clear risks as well as benefits. The authors review these risks and benefits in two sequential articles. In this first paper, they review the quantitative aspects of test accuracy (validity). In a sequential paper, to be published in next month's issue, they will discuss the risks and benefits of performing the test in various clinical circumstances.

The levels of the 2'-5' oligoadenylate enzyme synthetase in extracts of peripheral blood mononuclear cells from individuals with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) were measured and compared with synthetase levels in peripheral blood mononuclear cells (PBMs) from healthy heterosexual and homosexual controls. The mean basal synthetase level in heterosexual and homosexual controls was 14 +/- 13 and 12 +/- 9 pmol per hr/10(5) PBMs, respectively. Thirteen individuals with AIDS had a mean basal level of 129 +/- 75 pmol. Serial levels were persistently elevated in six of these individuals over a one- to 10-month period. Twelve of the 13 individuals had antibodies to human T cell lymphotrophic virus-III/lymphadenopathy-associated virus (HTLV-III/LAV). Thirty-three individuals with ARC had a mean basal synthetase level of 68 +/- 84 pmol. Thirty-two of the 33 had antibodies to HTLV-III/LAV. Eleven (33%) have had consistently normal synthetase levels (less than 2 SD above the mean for the homosexual controls, i.e., 30 pmol) over a three- to nine-month follow-up period. Fourteen (42%) had persistently elevated levels over the same period; four (29%) of these developed AIDS during the follow-up period. Eight have had fluctuating levels but have remained clinically well. These studies suggest that persistently elevated synthetase levels in individuals with ARC and antibodies to HTLV-III/LAV indicate progressive virus-induced disease activity. Elevated synthetase levels may be an important prognostic indicator of increased risk of progression to AIDS.

Following their first article on HIV-antibody tests,(1) the authors, in this second article, on HIV-antibody testing focus on the benefits and risks that may result from use of the tests. The sequelae of testing, especially if the result is positive, often differ widely, depending on the person tested and on those around him/her. Significant social and psychiatric risks may outweigh any medical benefit of testing, especially for certain persons known to be at high risk of HIV infection. Accordingly, a detailed protocol is suggested for managing both patient requests and physician-perceived indications for HIV-antibody testing. The authors outline the preferred approach to obtaining informed consent, a prerequisite, in their opinion, for ordering the tests.