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Biomedical subjects

G Ross

Publications and source records attributed to G Ross.

At least 73 records · Page 4Linked to original sources

Transplantation rate of the blood group B waiting list is increased by using A2 and A2B kidneys.

BACKGROUND: We have increased the transplantation rate for blood group B cadaveric waiting list candidates by transplanting them with A2 and A2B kidneys. METHODS: Since 1991, five of the seven renal transplant programs in our organ procurement organization service area have preferentially transplanted blood group A2 and A2B cadaveric kidneys to B blood group waiting list candidates with histories of low anti-A isoagglutinin titers. RESULTS: Between 1991 and 1997, these five centers performed transplantations on 71 patients from the B cadaveric waiting list. Of those 71 patients, 29% (21 of 71) underwent transplantation with either A2 (n=18) or A2B (n=3) cadaveric kidneys. In 1997 alone, 48% (11 of 23) of the B patient transplant recipients received A2 or A2B kidneys. CONCLUSIONS: Transplantation of A2 and A2B kidneys into B waiting list patients has successfully increased access of B patients to kidneys. Such an allocation algorithm implemented nationally may similarly increase the transplantation rate of B waiting list candidates.

ABO Blood-Group System↗

Long-term graft survival is improved in cadaveric renal retransplantation by flow cytometric crossmatching.

BACKGROUND: Cadaveric renal retransplantation is associated with a higher risk of early graft failure than primary grafts. A large proportion of those graft losses is likely attributable to donor-directed HLA class I antibodies, detectable by flow cytometry cross-matching but not by conventional crossmatching techniques. METHODS: Long-term graft survival in a group of 106 recipients of consecutive cadaveric renal regrafts between 1990 and 1997, in whom a negative flow T-cell IgG crossmatch was required for transplantation, was compared with two other groups of cadaveric transplant recipients. The first group consisted of 174 cadaveric regrafts transplanted between 1985 and 1995 using only a negative anti-human globulin (AHG) T-cell IgG crossmatch. The second group was primary cadaveric transplants done concurrently with the flow group (1990 to 1997) using only the AHG T-cell IgG crossmatch. RESULTS: The long-term (7 year) graft survival rate of flow crossmatch-selected regraft recipients (68%; n= 106) was significantly improved over that of regraft recipients who were selected for transplantation by only the AHG crossmatch technique (45%; n=174; log-rank=0.001; censored for patients dying with a functioning graft). Graft outcome for the flow cross-matched regraft recipients was not significantly different from that of primary cadaveric patients (72%; n=889; log-rank=0.2; censored for patients dying with a functioning graft). Finally, a positive B-cell IgG flow cytometric crossmatch had no influence on long-term regraft outcome. CONCLUSIONS: The use of the flow T-cell IgG cross-match as the exclusion criterion for cadaveric renal retransplantation yields an improved long-term graft outcome over that obtained when only the AHG cross-match is used and has improved survival of regraft recipients to the level of our primary cadaveric renal transplant population.

Adult↗

Influence of the Rh (D) blood group system on graft survival in renal transplantation.

BACKGROUND: The Rh (D) blood group system has not traditionally been considered to be a clinically relevant histocompatibility barrier in transplantation since conflicting results of its clinical importance have been reported. METHODS: We analyzed 786 consecutive primary cadaveric renal transplants performed by transplant centers in our Organ Procurement Organization (OPO) between 1990 and 1997. We also analyzed United Network for Organ Sharing (UNOS) data on 26,469 kidney transplants done from April 1994 to June 1996. RESULTS: Multivariate analysis revealed that Rh identity between the recipient and donor was significantly related to better graft outcome (risk ratio, 0.43; 95% confidence interval, 0.30 to 0.61; P=0.0001). Multivariate analysis of the UNOS data revealed that the Rh -/- group may have a positive influence on graft survival with a risk ratio of 0.43 (P=0.14). CONCLUSION: Multivariate analysis of primary cadaveric renal allografts performed within the Midwest Organ Bank OPO indicates that Rh (D) is a clinically relevant histocompatibility barrier that influences 7-year graft survival.

Blood Grouping and Crossmatching↗

Ten-year experience in transplantation of A2 kidneys into B and O recipients.

BACKGROUND: This article summarizes our 10-year multicenter experience with transplantation of 50 blood group A2 and A2B kidneys into B and O patients. METHODS: Since 1986, we have transplanted kidneys from 46 cadaver donors and 4 living donors who were blood group A2 (47 donors) or A2B (3 donors) into 19 B and 31 O patients. In 1991, we began allocating these kidneys preferentially to B and O recipients who were selected based on a history of low (< or =4) anti-A IgG isoagglutinin titers. Immunosuppression was no different from that used in ABO-compatible grafts. RESULTS: The 1-month function rate before thus selecting the patients was 68% (19/28), but is now 94% (17/18). Two-year cadaver-donor graft survival with this selection method is 94%, compared with 88% for 640 concurrent and consecutive ABO-compatible transplants (log-rank, 0.15). All four living-related transplants are still functioning, with a mean follow-up of 71 months. Since we began allocating A2 kidneys preferentially to B and O recipients, the percentage of the B patients who received A2 or A2B kidneys has increased from 29% (8/28) to 55% (10/18). CONCLUSIONS: Transplantation of A2 or A2B kidneys into B and O patients is clinically equivalent to that of ABO-compatible transplantation when recipients are selected by low pretransplant anti-A titer histories. This approach increases access of blood group B recipients to kidneys.

ABO Blood-Group System↗

The use of Acarbose in Type 2 diabetic patients in secondary failure: effects on glycaemic control and diet induced thermogenesis.

Acarbose, an alpha-glucosidase inhibitor, delays the absorption of complex carbohydrates and sucrose, thereby lowering post-prandial blood glucose. In this study, we evaluated the effects of Acarbose on glycaemic control in Type 2 diabetic patients in secondary oral hypoglycaemic agent failure. Due to its mode of action, we also used indirect calorimetry to examine its effects on energy expenditure (EE), diet induced thermogenesis (DIT) and respiratory quotient (RQ) after a standard breakfast (440 calories with 60 g carbohydrates). A total of 12 patients (male/female, 8/4; age, 56+/-9 years; duration of diabetes 10.1+/-4.6 years; body mass index (BMI) 29.6 + 2.7 kg/m2) with poor glycaemic control (HbA1c, 8.8+/-0.9%) completed 8 weeks treatment with Acarbose (100 mg). After treatment, HbAlc was lower compared to the baseline (8.8+/-0.9% vs. 8.0+/-0.9%; t = 2.7; P = 0.02). Acarbose acutely lowered post-prandial blood glucose and insulin area under the curve by a mean of 16.9% and 9.2%, respectively. Long term changes in HbA1c correlated strongly with acute changes in blood glucose area due to Acarbose administration (r = 0.87; P < 0.01). There was a significant effect of Acarbose on EE and DIT for the first 120 min post meal (F3,92 = 3.4; P = 0.03, F2,69 = 6.3; P = 0.008, respectively). After Acarbose treatment, RQ was lower at 30 min compared to the baseline (0.86+/-0.04 before, and 0.83+/-0.05 after; t = 2.8; P = 0.02). In conclusion, Acarbose improves glycaemic control and changes post-prandial energy expenditure of Type 2 diabetic patients in secondary failure. The magnitude of long term reduction in hyperglycaemia differs amongst individuals. This is largely due to intrinsic variations in patients' response to Acarbose rather than differences in medication compliance or dietary composition.

Acarbose↗

Permanent skin replacement using engineered epidermis containing fewer than 5% syngeneic keratinocytes.

This study was conducted to investigate permanent skin replacement using heterologous (syngeneic-allogeneic) epidermal substitutes containing fewer than 5% syngeneic keratinocytes. Keratinocytes were isolated from the skin of new-born Balb/c (B) and C3H/HeN (C) mice and cocultured in different ratios: 20%B-80%C, 10%B-90%C, 5%B-95%C, and 2%B-98%C (and vice versa). After 4 to 5 days, graftable epidermal substitutes were obtained and transplanted onto adult Balb/c or C3H/HeN male mice. Recipients always received the heterografts containing the lower percentage of their own keratinocytes. On Days 15 and 30 postgrafting, all heterografts showed significant graft take (> 75%) and skin replacement compared with allografts. Regenerated tissues were well structured and well vascularized. These tissues contained only syngeneic keratinocytes. These results led us to question whether this was an active immune situation. Structural analyses revealed the presence of leukocyte infiltration that was dependent on the percentage of allogeneic keratinocytes present in the heterologous implant. However, even with the 2% syngeneic-98% allogeneic implant, infiltration was lower than with the allograft. Leukocyte phenotyping confirmed the presence of immune cells infiltrating the heterologous implants and revealed the involvement of CD8+ and CD4+ lymphocytes in this immune activation. The percentages of these two cell populations were lower than those obtained with the allografts, suggesting moderate cellular activation after each heterograft compared with the allografts. In conclusion, it is possible to generate functional skin even after 2% syngeneic-98% allogeneic heterografts; there was moderate cellular immune activation compared with the allografts.

Animals↗

Ganciclovir-associated hypercalcemia in a renal transplant patient.

We describe a renal transplant patient who developed hypercalcemia during treatment with ganciclovir for cytomegaloviral (CMV) infection. To our knowledge such an association has not previously been reported. Hypercalcemia was associated with low levels of serum parathormone (PTH) and an increase in 1,25 dihydroxy vitamin D concentrations. The mechanism(s) of ganciclovir-associated hypercalcemia remains unclear.

Antiviral Agents↗

Absence of p53 permits propagation of mutant cells following genotoxic damage.

Much evidence has been gathered in support of a critical role for p53 in the cellular response to DNA damage. p53 dysfunction is associated with progression and poor prognosis of many human cancers and with a high incidence of tumours in p53 knockout mice. The absence of a p53-dependent G1 arrest that facilitates DNA repair or apoptosis might impact critically on clinical cancer in two ways. First, by abrogating the impact on therapy that operates via genotoxic damage and apoptosis; and second, by encouraging progression either by inducing genomic instability and DNA mis-repair or by permitting survival of mutants. However, experiments examining the relationship between p53 deficiency and mutation frequency have so far failed to confirm these predictions. The precise role played by p53 is therefore unclear. We now report use of a short term in vitro approach to assess the influence of p53 on radiation-induced mutations at the hprt locus in murine B cell precursors that are normally radiation ultrasensitive. We find a high number of hprt mutants among X-irradiated p53 null cells, which results from preferential survival as clonogenic mutants rather than from a p53-dependent increase in mutation rate. This result has important implications for genotoxic cancer therapy.

Animals↗

Psychoneuroimmunology.

This paper develops hypotheses regarding the interactions among stress, immunity, and chemical sensitivities and gives an overview of the questions and hypotheses generated by a working group exploring the application of psychoneuroimmunology to chemical sensitivities. Consideration is given to prospective longitudinal studies designed to find cases among at-risk exposed populations. Relevant immune parameters to be measured longitudinally and in challenge studies for patients with MCS are discussed. Immune system changes in response to the chronic stress of having MCS and as primary responses to chemical exposure also are considered.

Environment, Controlled↗

Evaluation of a critical pathway for stroke.

The diagnosis of stroke, which is diagnosis-related group (DRG) 014, is the fourth most frequent discharge DRG at Macomb Hospital Center, Warren, Michigan. The length of stay for stroke was 7.52 days before intervention. Quality improvement techniques identified areas of delay that presented opportunities for improvement. After the initiation of a critical pathway that begins its interventions in the Emergency Department, the length of stay decreased to 6.33 days. Quality of care was also improved in delivery time of carotid artery ultrasound examinations, as well as in timeliness of obtaining head computed tomography scans and reports. This article describes the development, implementation, and results of a stroke critical pathway that was implemented to address excessive length of stay.

Cerebrovascular Disorders↗

Lipid-lowering effects of fluvastatin in renal transplant patients. A clinical observation.

A Atherosclerosis-related cardiovascular disease remains an important cause of morbidity and mortality in renal transplant patients. We assessed the efficacy and safety of the newer synthetic HMG-CoA reductase inhibitor, fluvastatin, in 12 renal transplant patients who remained hypercholesterolemic, despite having been on the American Heart Association (AHA) Step I diet for 6 weeks. At 8 weeks, compared to the control phase, fluvastatin therapy, 20 mg/day, reduced the total cholesterol (TC) from 321 +/- 57 [+/-SD] to 301 +/- 123 mg/dl (p = 0.3); low-density lipoprotein cholesterol (LDL-C), from 209 +/- 56 to 176 +/- 81 mg/dl (p = 0.2); and the triglyceride (TG) levels from 343 +/- 119 to 277 +/- 117 mg/dl (p = 0.06); all these changes were statistically insignificant. However, the therapy significantly increased the high-density lipoprotein cholesterol (HDL-C) from 37 +/- 11 to 46 +/- 13 mg/dl (p = 0.006). During this short-term treatment period no adverse biochemical effects were noted with the therapy.

Adult↗

HLA-DR and DQ typing by polymerase chain reaction using sequence-specific primer mixes reduces the incidence of phenotypic homozygosity (blanks) over serology.

Because of the inherent difficulties in allele assignment with HLA-DR serological typing, in 1993 our organ procurement organization-based HLA laboratory replaced serology with the molecular method of polymerase chain reaction using sequence-specific primer mixes (PCR-SSP) to type for DR and DQ at a resolution level equivalent to that of serologically defined antigens. In this study, we compared the incidence of DR blanks, where allocative homozygosity occurred, and graft outcome during our serology epoch (1987-1993) with that of our molecular epoch (1993-1996). The incidence of DR blanks by PCR-SSP (17.0%; 138/1101) was significantly lower (P<0.005) than in the serology epoch (21.5%; 569/2647). Although DQ is not a component of the allocation algorithm, the incidence of blanks in the molecular era (21.9%; 196/895) was 46% lower (P<0.001) than in the serology epoch (40.8%; 931/2277). Graft survival in 163 cadaveric renal transplant recipients for whom molecular DR allocation occurred (patient and donor were molecularly typed) showed that PCR-SSP typing had no significant effect on 2.5-year graft survival for patients mismatched for 0 (97%), 1 (90%), or 2 (94%) HLA-DR antigens (P=0.4; log-rank). In conclusion, molecular typing lowered the rate of DR and DQ blanks, but molecular matching for HLA DR and DQ did not influence graft outcome at 2.5 years.

Blood Grouping and Crossmatching↗