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Biomedical subjects

A Kaan

Publications and source records attributed to A Kaan.

At least 19 recordsLinked to original sources
PubMed2005

Timing of the first endomyocardial biopsy in heart transplantation after induction immunosuppressive therapy--experience from Canadian Heart Transplant Centre.

BACKGROUND: The exact time point at which the first endomyocardial biopsy could be safely performed after the heart transplantation has not been systematically studied. In an attempt to determine this time point in our population, the number and severity of acute rejection episodes in the first eight weeks after the heart transplantation were assessed in 91 patients who underwent the procedure at St Paul's Hospital, Vancouver between September 1996 and December 2002. METHODS AND RESULTS: For the purpose of our analysis, acute rejection was defined as the grade > or =2 according the International Society for Heart and Lung Transplantation (ISHLT). Three hundred and sixty two endomyocardial biopsies were performed in 87 patients surviving to the first biopsy from one to eight weeks after the heart transplantation. In 85 patients who received induction immunosuppressive therapy, 13 episodes of acute rejection were identified. In two patients who did not receive the induction therapy, three episodes of acute rejection occurred. Acute rejection grade ISHLT 3 was found in 2 patients who did not receive induction therapy and in three patients who did. ISHLT grade 4 rejection occurred at weeks 5 and 7 in two patients who received induction therapy. Only one patient who received induction therapy had acute rejection within the first three weeks after the heart transplantation. CONCLUSIONS: Our analysis reveals that the frequency of acute rejection within the first eight weeks after the heart transplantation using induction therapy is low in this cohort, suggesting that the first routine endomyocardial biopsy could be delayed until the week four post-transplant.

Adult↗
PubMed2001

Pharmacokinetics of cyclosporine in heart transplant recipients receiving metabolic inhibitors.

BACKGROUND: Inhibitors of cyclosporine metabolism are commonly co-administered with cyclosporine in transplant recipients. The aim of this study was to compare cyclosporine pharmacokinetics using the conventional formulation (Sandimmune) and after switching to the microemulsion (Neoral) formulation, in stable heart transplant recipients receiving various cyclosporine metabolic inhibitors. METHODS: Steady-state blood concentration-time profiles of Sandimmune were studied in 47 transplant recipients receiving either cyclosporine alone (Group A, n = 11) or in combination with diltiazem (120 mg/day, Group B, n = 11), ketoconazole (200 mg/day, Group C, n = 13), or both ketoconazole and diltiazem (200 and 120 mg/day, respectively, Group D, n = 12), and restudied 1 week after switching to Neoral. RESULTS: Neoral resulted in more rapid cyclosporine absorption as judged by the shorter absorption half-lives in all groups (p < 0.05). The mean percentage increase in the values of area-under-the-concentration-time curve was 42% and 37.5% higher for Neoral compared with Sandimmune for Groups A and B, respectively, but only 5.4% higher for Group C and 9.5% higher for Group D. The mean morning trough concentration of cyclosporine was not significantly different after administration of Neoral compared with Sandimmune in any of the groups studied (179 vs. 167 microg/liter for Group A; 171 vs. 147 microg/liter for Group B; 189 vs. 194 microg/liter for Group C; and 181 vs 201 microg/liter for Group D). Neoral did not alter serum concentrations of sodium, potassium, creatinine, and urea in any of the study groups. CONCLUSIONS: The faster absorption and improved bioavailability of cyclosporine (around 40%) with Neoral compared with Sandimmune was not seen in patients receiving ketoconazole, where in fact cyclosporine bioavailability was already maximal. Mean morning trough levels of cyclosporine did not reflect the improvement in bioavailability seen in patients switching from Sandimmune to Neoral. Cyclosporine dose adjustment may be needed when switching from Sandimmune to Neoral for patients not receiving sparing agents or who receive diltiazem, but trough levels cannot necessarily be relied upon to determine the degree of adjustment needed. For patientson ketoconazole, the absorption profile is already optimized and no dosage alteration seems necessary.

Calcium Channel Blockers↗
PubMed2001

Improvement in quality of life outcomes 2 weeks after left ventricular assist device implantation.

BACKGROUND: The successful use of left ventricular assist devices (LVADs) as a bridge to heart transplantation has prompted our examination of quality of life (QOL) outcomes. The purposes of this study are to describe QOL in patients 1 to 2 weeks after LVAD implantation and to compare QOL in a smaller cohort of patients from before to 1 to 2 weeks after surgery. METHODS: Data were collected from a convenience sample of 81 patients who completed booklets of questionnaires that measure domains of QOL 1 to 2 weeks after LVAD insertion and from 30 of 81 patients who completed booklets at both the pre-implantation and post-implantation periods. Patients completed booklets of 6 to 8 self-reporting instruments, with acceptable reliability and validity. Data were analyzed using descriptive and comparative statistics (chi-square, Mann-Whitney U and Wilcoxon signed ranks tests) with p = 0.01 considered statistically significant. RESULTS: One to 2 weeks after LVAD implantation, patients were quite satisfied with their lives, experienced moderately low amounts of stress, coped well, and perceived themselves as having good health and QOL, low symptom distress, and moderately low functional disability. Patients reported significantly better QOL, more satisfaction with health and functioning, and were significantly less distressed by symptoms from immediately pre-operatively to post-operatively. However, patients reported significantly more self-care disability and more dissatisfaction with socioeconomic areas of life from before to immediately after surgery. Psychological distress was low and did not change with time. CONCLUSION: Given that QOL improved from before to after LVAD implantation, our findings provide a springboard for investigation of the impact of LVADs on long-term QOL outcomes.

Adult↗
PubMed2000

Efficacy and safety of pravastatin vs simvastatin after cardiac transplantation.

Prior studies of cardiac transplant recipients have shown that pravastatin reduces 12-month rejection and mortality after cardiac transplantation and simvastatin reduces 4-year mortality, low-density lipoprotein (LDL) cholesterol levels, and intimal thickening. In a 12-month observational study, cardiac transplant recipients received open-label pravastatin 40 mg (n = 42) or simvastatin 20 mg daily (n = 45) on an alternating basis from the time of transplantation. Lipid levels, safety, and post-transplant outcomes were compared. We found no significant differences in total LDL or high-density lipoprotein cholesterol, triglycerides, linearized infection or rejection rates, liver function tests, or immunosuppressant dosages between groups at 1, 3, 6, or 12 months. Rhabdomyolysis or myositis occurred only in patients on simvastatin (n = 6, 13.3%) with no episodes for patients on pravastatin (p = 0. 032). Survival at 12 months on an actual treatment basis was 97.6% for patients on pravastatin and 83.7% for those on simvastatin (p = 0.078). Immunosuppression-related deaths occurred in only 2.4% (1 patient) on pravastatin vs 15.6% (n = 7) on simvastatin (p = 0.06). Pravastatin and simvastatin resulted in comparable lipid profiles. Pravastatin use was however free from the high rates of rhabdomyolysis and myositis seen with simvastatin use. Pravastatin was additionally associated with a trend toward superior survival, attributable to fewer immunosuppression-related deaths. For safety and pharmacokinetic reasons, pravastatin should be considered the statin of choice after heart transplantation.

Cholesterol, HDL↗
PubMed2000

Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months.

BACKGROUND: The value of cord blood IgE in predicting the development of asthma and other IgE-mediated allergic diseases is unclear. OBJECTIVE: The purpose of this study is twofold: (1) to determine factors affecting cord blood IgE level and (2) to determine whether cord blood IgE predicts the development of asthma and other IgE-mediated allergic diseases in high risk (defined as those with at least one first degree relative with asthma or 2 first degree relatives with other IgE-mediated allergic diseases) infants at 12 months. METHODS: The study utilized cord blood obtained from a group of high risk infants who took part in a randomized controlled trial to assess the effectiveness of an intervention program in the primary prevention of asthma and other IgE-mediated allergic diseases. Total IgE and cotinine in the cord blood were measured. Assessment of the infants was done at 12 months for these diseases. RESULTS: Sixty-four (17.8%) infants had detectable total IgE in cord blood >0.5 kU/L. The proportion of infants with elevated cord blood IgE was significantly higher among nonwhites, birth during winter months, and those with a maternal history of asthma. There was no correlation between cord blood IgE and cord blood cotinine level. Cord blood IgE was found to be a significant predictor for the development of urticaria due to food allergy but not for other outcomes. CONCLUSION: Both genetic and environmental risk factors play a role in determining the level of IgE in cord blood. Cord blood IgE was a significant risk factor for the development of urticaria due to food allergy at 12 months of life. As urticaria due to food allergy is a prodrome for anaphylaxis, measurement of IgE in cord blood may be indicated in infants at high risk for developing allergic diseases so that preventive measures can be applied.

Adult↗
PubMed1997

Conventional and saturation-transfer EPR of spin-labeled mutant bacteriophage M13 coat protein in phospholipid bilayers.

A mutant of bacteriophage M13 was prepared in which a cysteine residue was introduced at position 25 of the major coat protein. The mutant coat protein was spin-labeled with a nitroxide derivative of maleimide and incorporated at different lipid-to-protein (L/P) ratios in DOPC or DOPG. The rotational dynamics of the reconstituted mutant coat protein was studied using EPR and saturation transfer (ST) EPR techniques. The spectra are indicative for an anisotropic motion of the maleimide spin label with a high order parameter (S = 0.94). This is interpreted as a wobbling motion of the spin label with a correlation time of about 10(-6) to 10(-5) s within a cone, and a rotation of the spin label about its long molecular axis with a correlation time of about l0(-7) s. The wobbling motion is found to correspond generally to the overall rotational motion of a coat protein monomer about the normal to the bilayer. This motion is found to be sensitive to the temperature and L/P ratio. The high value of the order parameter implies that the spin label experiences a strong squeezing effect by its local environment, that reduces the amplitude of the wobbling motion. This squeezing effect is suggested to arise from a turn structure in the coat protein from Gly23 to Glu20.

Capsid↗
PubMed1997

Come fly with me.

We have both worked performing medical retrievals of tourists who have become injured or sick overseas and required a nursing escort. Back to Australia, such services are covered by travel insurance policies. Through this work we have had the opportunity to visit, albeit briefly, some beautiful places with some fantastic health care facilities (we use the term 'fantastic' in the entire spectrum of its meaning!). All our adventurous stories are true, but those recounted here are an amalgam of a number of trips and a number of patients. The places, names and diagnoses of patients have been changed to protect the hospitals, and those people in our care.

Australia↗
PubMed1995

Ketoconazole to reduce the need for cyclosporine after cardiac transplantation.

BACKGROUND: Because ketoconazole can markedly reduce the need for cyclosporine and because it also has antimicrobial properties, it may offer benefits in the treatment of patients after cardiac transplantation. METHODS: We randomly assigned 43 patients at the time of cardiac transplantation to receive ketoconazole (200 mg per day) (23 patients) or no ketoconazole (20 patients). The main end points were the dose of cyclosporine required and the incidence of cardiac rejection and infection. RESULTS: Ketoconazole reduced the dose of cyclosporine needed to maintain target levels by 62 percent at one week and by 80 percent at one year. The cost savings per patient (in U.S. dollars, inclusive of the cost of ketoconazole) was about $5,200 in the first year and about $3,920 in each subsequent year. The mean (+/- SD) rate of rejection in the first month was lower in the ketoconazole group than in the controls (4.2 +/- 0.8 vs 5.7 +/- 1.0 episodes per 100 patient-days, P < 0.001), and the average number of days to the first rejection was higher (30 +/- 29 vs. 15 +/- 8, P = 0.03). In the first year, 22 percent of the ketoconazole group required cytolytic therapy, as compared with 35 percent of the controls, and 9 percent of the ketoconazole group required total lymphoid irradiation, as compared with 15 percent of the controls (P = 0.07). The incidence of infection was lower in ketoconazole-treated patients than in controls in the second month (1.4 +/- 0.5 vs. 2.8 +/- 0.7 episodes per 100 patient-days, P < 0.001) and in the third month (0.8 +/- 0.3 vs. 2.3 +/- 0.6 episodes per 100 patient days, P < 0.001). Transient, asymptomatic cholestasis was observed in the ketoconazole group. CONCLUSIONS: After cardiac transplantation, ketoconazole greatly reduced the need for cyclosporine, resulting in substantial cost savings. Ketoconazole also reduced the rates of rejection and infection, without persistent toxic effects. We now use ketoconazole routinely in cardiac-transplant recipients.

Actuarial Analysis↗
PubMed1994

Secondary structure of the single-stranded DNA binding protein encoded by filamentous phage Pf3 as determined by NMR.

Nuclear magnetic resonance spectroscopy was employed to study the single-stranded DNA binding protein encoded by the filamentous Pseudomonas bacteriophage Pf3. The protein is 78 amino acids long and occurs in solution predominantly as a homodimer with a molecular mass of 18 kDa. Sequence-specific 1H and 15N resonance assignments have been obtained using homo- and heteronuclear two- and three-dimensional experiments. The secondary structure of the protein monomer was determined from a qualitative interpretation of nuclear Overhauser enhancement spectra and amide exchange data. It consists of a five-stranded antiparallel beta-sheet and three beta-hairpins. Problems caused by the protein's tendency to aggregate at concentrations needed for NMR spectroscopy were largely overcome by designing a mutant (Phe36-->His) which exhibits significantly improved solubility characteristics over the wild-type protein. It is shown that this mutation only locally affects the structure of the protein; the chemical shifts of the wild-type and mutant species differ only for a few residues near the site of the mutation, and the secondary structures of the proteins are identical. The secondary structure of the Pf3 single-stranded DNA binding protein is compared to that of the Ff gene V protein, the only single-stranded DNA binding protein for which the complete three-dimensional structure is known to date [Folkers, P. J. M., Nilges, M., Folmer, R. H. A., Konings, R. N. H. & Hilbers, C. W. (1994) J. Mol. Biol. 236, 229-246; Skinner, M. M., Zhang, H., Leschnitzer, D. H., Guan, Y., Bellamy, H., Sweet, R. M., Gray, C. W., Konings, R. N. H., Wang, A. H.-J. & Terwilliger, T. C. (1994) Proc. Natl Acad. Sci. USA 91, 2071-2075]. It is found that the secondary structures of the two proteins are very similar which supports the hypothesis that a five-stranded antiparallel beta-sheet with protruding beta-hairpins is a common motif in a certain class of single-stranded DNA binding proteins. In addition, the sequence and folding predicted earlier for the DNA binding wing in the single-stranded DNA binding protein of phage Pf3 [de Jong, E. A. M., van Duynhoven, J. P. M., Harmsen, B. J. M., Tesser, G. I., Konings, R. N. H. & Hilbers, C. W. (1989) J. Mol. Biol. 206, 133-156] is borne out by the present study. It closely resembles that in the single-stranded DNA binding protein of phage Ff, which may indicate that such a wing is a recurrent motif as well.

Amino Acid Sequence↗
PubMed1992

The Australian and New Zealand Cardiothoracic Organ Transplant Registry: first report 1984-1992.

This initial report of the Australian and New Zealand Cardiothoracic Organ Transplant Registry summarises the results of all cardiothoracic transplants performed between February 1984 and April 1992. A total of 549 first cardiothoracic transplant procedures and six cardiac retransplant operations were performed in five transplant units throughout Australia and New Zealand. There were 466 orthotopic cardiac transplants and one heterotopic transplant with overall survival 86% at one year and 80% at five years. Two of six patients who underwent cardiac retransplantation are alive. Fifty-three heart-lung transplants were performed with 72% one year and 42% five year survival. Twenty-nine single lung transplant procedures were undertaken, with actuarial survival 72% at 12 months. Factors influencing waiting period and post-transplant survival for each type of procedure are detailed. The relative lack of donors compared with recipient demand has produced increased waiting times for every type of cardiothoracic organ transplant.

Actuarial Analysis↗
PubMed1991

Regulation of expression of the genome of bacteriophage M13. Gene V protein regulated translation of the mRNAs encoded by genes I, III, V and X.

With the aid of a binary plasmid in vivo testsystem it was demonstrated that the single-stranded DNA binding protein encoded by gene V of bacteriophage M13 not only regulates the synthesis of its cognate DNA replication proteins at the level of translation, but also of the assembly proteins and the coat proteins encoded by genes I and II, respectively. Furthermore, gene V protein functions as a translational autoregulator of its own synthesis. Comparison of the mRNA levels of genes I and X in the presence and absence of wild-type gene V protein indicated that gene V protein augments the physical stability of these mRNAs. The expression of the Escherichia coli beta-galactosidase gene and of a gene X mutant containing a deletion in the nontranslated mRNA leader sequence was not influenced by gene V protein, lending support to the conclusion that gene V protein exerts its regulatory effect via a specific nucleotide sequence in the leader sequences of the respective M13 mRNAs. We conclude that gene V protein functions as a master regulatory protein of the expression and replication of the M13 genome.

Autoradiography↗
PubMed1989

hyd gamma, a gene from Desulfovibrio vulgaris (Hildenborough) encodes a polypeptide homologous to the periplasmic hydrogenase.

Downstream of the genes for the structural alpha and beta subunits of the periplasmic Desulfovibrio vulgaris (Hildenborough) hydrogenase a DNA fragment was detected with sequence homology to these genes. This fragment was cloned in Escherichia coli and the nucleotide sequence was determined. A gene was detected on the fragment with coding capacity for a 65.8 kDa polypeptide, hyd gamma. The central part of hyd gamma has an unusually high degree of homology with the alpha subunit and the C-terminal part has similarity with the beta subunit. These results strongly suggest that the three genes for hyd gamma and the alpha and beta subunits derive from one common ancestor gene. We succeeded in the identification of the translational product of this gene in E. coli, but were unable to determine the function of hyd gamma after expression in E. coli.

Amino Acid Sequence↗
PubMedDate not supplied

HLA mismatching and outcome in heart, heart-lung, and single lung transplantation.

BACKGROUND: To determine the influence of HLA mismatching on rejection after cardiothoracic organ transplantation, we analyzed results in 243 recipients. METHODS: There were 183 heart, 25 heart-lung, and 35 single lung recipients, all receiving triple-drug immunosuppression with anti-thymocyte globulin induction. Zero, one, and two mismatches occurred by chance at each locus in between 0% to 9%, 26% to 35%, and 47% to 70% of recipients, respectively. RESULTS: In heart recipients, compared with a two mismatch, a zero mismatch was associated with a lower linearized rejection rate in the first 6 months. A zero B locus mismatch was likewise associated with less rejection in month 1, and DR zero mismatch with reduced rejection in the first 3 months. Steroid withdrawal was more successful in those with zero mismatch at any locus. In heart-lung recipients linearized rejection was significantly lower in those with lesser degrees of A and DR locus mismatching, and after single-lung transplantation linearized rejection was significantly lower with lesser degrees of A and B locus mismatching from 3 to 6 months only. Actuarial survival did not differ for any organ with any degree of mismatch at any locus. CONCLUSIONS: HLA mismatching affects rejection, but the effect is limited to the early postoperative period for heart and heart-lung recipients. Lower grades of mismatch increase the likelihood of successful steroid withdrawal for heart recipients. The chance occurrence of no mismatch at any locus is rare, making prospective matching infeasible. HLA mismatching identifies patients at higher risk of rejection. The best use of this information may be to guide early immunosuppression, limiting prospective matching to retransplants or with presensitized recipients.

Graft Rejection↗
PubMedDate not supplied

Outcome in peripartum cardiomyopathy after heart transplantation.

From 1983 to 1991, 27 women with peripartum cardiomyopathy were considered for heart transplantation. Of 27 patients, 11 (41%) improved with medical therapy, 10 (37%) underwent transplantation, and six (22%) died. Results in the 10 patients with peripartum cardiomyopathy who underwent transplantation were compared with results in 39 women who underwent transplantation for dilated cardiomyopathy (idiopathic, Adriamycin, valvular, or familial) to determine whether there were differences in survival, rejection, or infection rates. The two groups were, by chance, well matched for number of pregnancies, peak panel reactivity, and cross-match. Mean time from delivery to transplantation was 24 weeks (range 2 to 188 weeks), and this time did not correlate with rejection rates. The linearized rate of rejection from 0 to 3 months was 30% higher in the group with peripartum cardiomyopathy (3.4 +/- 0.7 vs 2.6 +/- 0.3 episodes/100 patient days; p = 0.05). The mean postoperative day to first rejection was day 26 for peripartum cardiomyopathy and day 28 for women with dilated cardiomyopathy. Rejection requiring cytolytic therapy occurred in 40% of women with peripartum cardiomyopathy and 21% of the comparison group (difference not significant). Linearized (treated) infection rates were 1.8 +/- 0.5 for the group with peripartum cardiomyopathy versus 1.5 +/- 0.2 episodes/100 patient days for others (p = 0.05). Actuarial survival was excellent in both groups with 88% and 86% 2-year survival rates, respectively. In conclusion, women who undergo transplantation for peripartum cardiomyopathy have a 30% higher rate of early rejection than do those who undergo transplantation for idiopathic cardiomyopathy and tend to have a greater need for cytolytic therapy. Infection rates are consequently higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMedDate not supplied

Outcome in paired recipients of single lung transplants from the same donor.

BACKGROUND AND METHODS: We compared outcome measures in twenty single lung transplant recipients: 10 patients received the first lung of a donor pair (group 1), and 10 patients received the second lung (group 2) to determine the feasibility of sequential use, respectively, of donor lungs from the same donor in the same institution. The paired recipients underwent transplantation in the same operating room by the same surgical team. Both groups were well matched for age, gender, pretransplantation symptom class and diagnosis. RESULTS: The ischemic time for group 1 versus group 2 was 164 +/- 53 minutes (mean +/- standard deviation) (range 103 to 250 minutes) versus 377 +/- 53 minutes (range 315 to 445 minutes), respectively, (p < 0.001), but the longer ischemic time for group 2 did not adversely affect time to extubation (10.5 +/- 5.1 hours versus 10.3 +/- 7.6 hours; p = Not significant), early gas exchange (partial pressure of arterial oxygen on a fractional concentration of oxygen in inspired gas of 0.60: 237 +/- 61 versus 267 +/- 88 mm Hg; p = Not significant), length of hospital stay (16 +/- 13 days versus 16 +/- 5 days; p = Not significant), or actuarial one-year survival (80 +/- 12% versus 90 +/- 12%; p = Not significant). However, acute lung rejection (expressed as events/100 days) was more common within the first 3 months in group 1 versus group 2 (2.68 +/- 0.57 versus 1.32 +/- 0.38, respectively; p < 0.01), as were infectious events (2.07 +/- 0.50 versus 0.99 +/- 0.33; p < 0.01). CONCLUSIONS: These data confirm the safety of using the second lung from a donor pair sequentially in the same institution. The longer cold ischemic time for the second lung does not impair demonstrably early graft function and may be associated with a lower perioperative morbidity from acute rejection and subsequent infection. One-year outcome appears favorable for both groups.

Adolescent↗