Autonomic function assessed by heart rate variability is normal in Alzheimer's disease and vascular dementia.

Heart rate variability (HRV) is a sensitive method for the assessment of autonomic function and requires little cooperation from the subject, making it suitable for use in dementia. Preliminary studies have suggested that HRV may be impaired in Alzheimer's disease (AD). HRV has not been studied in vascular dementia (VAD). We investigate autonomic function in AD and VAD, using power spectral analysis of HRV. One hundred and fourteen participants were evaluated (14 AD, 20 VAD and 80 controls). The resting ECG was recorded for 5 min with participants in the supine position. Power spectral analysis used to obtain spectral bands in the very-low-frequency (<0.04 Hz), low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.40 Hz) bands and total spectral power (<0.40 Hz) according to international HRV guidelines. There were no differences in HRV in patients with AD or VAD when compared with controls.

Caudal differential pressure as a predictor of swimming speed of cod (Gadus morhua).

We report the results of an experiment designed to investigate the feasibility of using differential pressure to estimate the swimming speed and metabolic rate of Atlantic cod (Gadus morhua). Seven cod were fitted with a miniature differential pressure sensor mounted on one side of the caudal peduncle immediately anterior to the base of the caudal fin rays. Relationships between differential pressure, tailbeat frequency, tailbeat amplitude, swimming speed and rate of oxygen consumption ((O(2))) were determined as a function of the swimming speed of cod swimming at 5 degrees C in a recirculating 'Brett-style' respirometer. Tailbeat differential pressure, tailbeat amplitude and tailbeat frequency were highly correlated with swimming speed. The average or integrated pressure ranged from 0 to 150 Pa for speeds up to 0.8 m s(-1) (1.1 L s(-1), where L is total body length), while the 'pressure difference' (maximum minus minimum pressure) ranged from 0 to 900 Pa. Small changes in swimming speed of less than 0.05 m s(-1) were readily detected as differences in tailbeat pressure. Burst swimming in the respirometer resulted in huge pressure 'bursts' of up to 5000 Pa 'pressure difference'. The rate of oxygen consumption increased exponentially and was highly correlated with swimming speed (r(2)=0.77). The rate of oxygen consumption was also correlated with tailbeat integrated pressure (r(2)=0.68) and with differential pressure (r(2)=0.43); regression correlations were always greater for individuals than for combined data from all cod. The results detailed in this study indicate that an ultrasonic differential pressure transmitter would enable accurate estimates of the swimming speed, rates of oxygen consumption and activity patterns of free-ranging fish in nature.

Peri-operative cardiac morbidity in kidney transplant recipients: incidence and risk factors.

BACKGROUND: Renal transplant recipients are known to be at increased risk for developing cardiac disease. In both general and peripheral vascular surgery, pre-operative risk stratification (and intervention when indicated) has decreased the incidence of peri-operative cardiac complications. In this study, we set out to identify subsets of patients at high risk for peri-operative cardiac complications after a renal transplant. METHODS: We retrospectively reviewed the records of 2694 adult renal transplants performed at the University of Minnesota between January 1, 1985 and December 31, 1998. We determined the incidence of peri-operative (within 30 d post-transplant) cardiac complications, including myocardial infarction (MI). Risk factors for the development of these complications were determined by multivariate analysis. RESULTS: We found 163 peri-operative cardiac complications, for an overall incidence of 6.1%. Specific cardiac complications included MI (n=43, 1.6%), arrhythmia (n=74, 2.7%), angina (n=31, 1.2%), cardiac arrest (n=13, 0.5%), and congestive heart failure (n= 2, 0.1%). By multivariate analysis, significant risk factors for any cardiac complication were age> or =50 yr (relative risk (RR)=3.0, p=0.0001) and pre-transplant cardiac disease (RR=3.3, p=0.0001). Not significant were diabetes mellitus (DM), cadaver donor source, pre-transplant dialysis, a history of smoking, and hypertension. Significant risk factors for peri-operative MI were age> or =50 yr, pre-existing cardiac disease, and DM. Diabetic patients with pre-existing cardiac disease were at especially high risk for peri-operative cardiac events. CONCLUSIONS: Patients>50 yr and those with pre-existing cardiac disease, especially if diabetic, are at significantly increased risk for developing peri-operative cardiac complications after a renal transplant. Such patients require aggressive pre-operative investigations, which may include coronary angiography, to decrease the risk of post-transplant complications.

Aerobic and anaerobic swimming performance of individual Atlantic cod.

Individual Atlantic cod (Gadus morhua) were exercised using three different measures of swimming performance. (1) An endurance test (critical swimming speed, U(crit), protocol) designed to assess predominantly aerobic endurance swimming (duration hours). (2) An acceleration test (U(burst)), in which the fish were required to swim against a rapidly increasing current until exhausted (duration minutes). This test was designed to assess predominantly glycolytic-based swimming capacity. (3) A sprint test that examined the animals' ability to swim away from a sudden stimulus (duration seconds). Rates of oxygen consumption ( mdot (O2)) during the endurance test and various morphological variables of the individual fish were also measured. Both aerobic and anaerobic swimming performance of individual cod were found to be significantly repeatable over a 3 month period. mdot (O2) during the U(crit) protocol was also significantly repeatable at intermediate to high swimming speeds, but not at low speeds. Our results support extrapolation from metabolic rates at incremented swimming speeds to zero activity as the best way to measure standard metabolic rate in cod. While performance in the U(crit) test and the sprint test were positively correlated, there was a negative correlation between performance in the U(crit) test and performance in the U(burst) test. This implies a potential trade-off in individual cod between stamina and the ability to use glycolytic-based locomotion. Inter-individual variation in swimming performance during these protocols, while substantial, was not correlated with individual variation in fin surface areas, age or morphology. However, U(burst) performance was dependent upon the sex of the animals, while performance during the U(crit) protocol was significantly correlated with their aerobic scope for activity.

Living donors >55 years: to use or not to use?

BACKGROUND: Kidney transplants using older donors are becoming increasingly accepted as a strategy for alleviating the growing donor organ shortage. Most studies to date have shown decreased graft survival associated with the use of older cadaver donors; however, studies on the effect of living donor age on graft survival are less clear-cut. METHODS: We studied the effect of donor age on patient and graft survival after 1126 consecutive cyclosporine-treated primary kidney transplants performed between January 1, 1985 and December 31, 1995. Of these grafts, 598 were from living donors (74 from donors >55 years old) and 528 from cadaver donors (54 from donors >55 years). We calculated actuarial patient survival, graft survival, and death-censored graft survival for recipients of both living donor and cadaver kidneys. Living donors were then further divided by HLA mismatch (0 vs. 1 - 6) and the presence or absence of an acute rejection episode. Multivariate analysis of factors associated with decreased graft survival was performed for recipients of both living and cadaver donor kidneys. Factors included for analysis were donor age >55 years, recipient age >50 years, the presence of diabetes mellitus, HLA mismatch (0 vs. 1 - 6), and the presence of an acute rejection episode. RESULTS: For cadaver kidneys, univariate analysis indicates that both overall (P=0.004) and death-censored (P=0.001) graft survival was significantly better with younger cadaver kidneys. This is supported by our multivariate analysis, which shows that cadaver donor age >55 years is an independent predictor of poor actuarial graft survival (P=0.0003). For living donor kidneys, univariate analysis also indicates that both overall (P=0.045) and death-censored (P=0.005) graft survival was significantly better with younger living donor kidneys. However, in the absence of acute rejection, 10-year death-censored graft survival for patients with older vs. younger living donor kidneys was 93% vs. 94%, whereas in the presence of one or more acute rejection episodes, 10-year death-censored graft survival dropped markedly to 39% with older and 54% with younger living donors. Kidneys from living donors >55 years had significantly better long-term graft survival than cadaver donors >55 years (P=0.012) and had comparable graft survival to younger cadaver donors. In contrast to our univariate analysis, multivariate analysis of our living donor data shows that decreased actuarial living donor death-censored graft survival was significantly associated only with the presence of one or more acute rejection episodes (P<0.0001). Living donor age >55 years was not independently associated with decreased graft survival. CONCLUSIONS: Ours is the largest single-center study of outcome for recipients of kidneys from living donors >55 years. Using univariate analysis, we have shown that graft survival of kidneys from older living donors is significantly better than that of kidneys from older cadaver donors and is comparable to that of kidneys from younger cadaver donors. Using multivariate analysis, we have shown that the presence of one or more acute rejection episodes significantly shortens both cadaver and living donor long-term graft survival. Most significantly, we have shown that, although the use of kidneys from cadaver donors >55 years is associated with significantly decreased long-term graft survival, no such association exists for recipients of kidneys from living donors >55 years. We feel that our data support the continued use of kidneys from older living donors.

Long-term follow-up of living kidney donors: quality of life after donation.

The University of Minnesota has been a strong advocate of living donor kidney transplants. The benefits for living donor recipients have been well documented. The relative low risk of physical complications during donation has also been well documented. Less well understood is the psychosocial risk to donors. Most published reports have indicated an improved sense of well-being and a boost in self-esteem for living kidney donors. However, there have been some reports of depression and disrupted family relationships after donation, even suicide after a recipient's death. To determine the quality of life of our donors, we sent a questionnaire to 979 who had donated a kidney between August 1, 1984, and December 31, 1996. Of the 60% who responded, the vast majority had an excellent quality of life. As a group, they scored higher than the national norm on the SF-36, a standardized quality of life health questionnaire. However, 4% were dissatisfied and regretted the decision to donate. Further, 4% found the experience extremely stressful and 8% very stressful. We used multivariate analysis to identify risk factors for this poor psychosocial outcome and found that relatives other than first degree (odds ratio=3.5, P=0.06) and donors whose recipient died within 1 year of transplant (odds ratio=3.3, P=0.014) were more likely to say they would not donate again if it were possible. Further, donors who had perioperative complications (odds ratio=3.5, P=0.007) and female donors (odds ratio=1.8, P=0.1) were more likely to find the overall experience more stressful. Overall, the results of this study are overwhelmingly positive and have encouraged us to continue living donor kidney transplants.

Mouse-to-rabbit xenotransplantation: a new small animal model of hyperacute rejection mediated by the classical complement pathway.

BACKGROUND: Hyperacute rejection of porcine organs transplanted into primate recipients is initiated by the binding of preformed xenoreactive natural antibodies to the vascular endothelium of the graft and activation of the classical complement pathway. Several small animal models are currently employed to study various aspects of xenograft rejection; however, none has been shown to manifest hyperacute rejection mediated by the classical pathway of complement activation. METHODS: We performed heterotopic mouse heart transplants into weanling rabbits, adult rabbits, and C6-deficient rabbits. The recipients received no immunosuppression. Rejected grafts were subjected to histologic analysis and immunofluorescence staining for rabbit IgG, IgM, and C3. Levels of preexisting cytotoxic antibodies as well as classical and alternative complement pathway activities were determined in rabbit serum using mouse red cells as targets. RESULTS: Mean graft survival was 37+/-9.6 min for mouse-to-weanling rabbit transplants (n=10), and 40+/-11.1 min for mouse-to-adult rabbit transplants (n=5). Rejected grafts showed diffuse interstitial hemorrhage, endothelial cell damage, myocyte necrosis, moderate diffuse deposition of rabbit IgG, and dense deposition of rabbit IgM and C3 on the vascular endothelium of the graft, consistent with hyperacute rejection. One mouse-to-C6-deficient rabbit transplant was rejected at 21 hr with severe interstitial hemorrhage, cellular necrosis and a moderate cellular infiltrate consisting primarily of neutrophils and some mononuclear cells. A second transplant in a C6-deficient rabbit was functioning when the recipient died at 6.5 hr as a result of complications of surgery; the graft had normal myocytes and vasculature with minimal spotty interstitial hemorrhage. Both weanling and adult rabbit serum were found to have high titers of cytotoxic IgM anti-mouse antibodies and strong classical complement pathway activity with minimal alternative pathway activity towards mouse red cells. CONCLUSIONS: The mouse-to-rabbit species combination manifests hyperacute xenograft rejection. In vitro studies suggest that this process is mediated by IgM anti-mouse natural antibodies and activation of the classical pathway of complement.

Effect of early cyclosporine levels on kidney allograft rejection.

Acute rejection is the greatest risk factor for development of biopsy-proven chronic rejection and late kidney allograft loss. We previously noted that low cyclosporine (CsA) levels were a risk factor for early acute rejection in pediatric recipients (1). In our current study, we used logistic regression to identify risk factors for acute rejection in 726 adult kidney transplant recipients on triple therapy (prednisone, azathioprine, CsA). Variables considered for logistic regression analysis were donor organ source (cadaver vs. living), degree of HLA mismatch (1 to 6 vs. 0 antigen mismatch), transplant number (primary vs. retransplant), CsA levels (< 125 vs. > or = 125 ng/ml, < 150 ng/ml vs. > or = 150 ng/ml, and < 175 vs. > or = 175 ng/ml), and acute rejection episodes (0 vs. > or = 1). Of 726 recipients, 401 (55%) received cadaver kidneys; 325 (45%), living related. Overall, 572 (79%) had a primary transplant; 154 (21%), a retransplant. The vast majority of acute rejection episodes occurred within the first 2 months posttransplant; 68% of recipients had no acute rejection episodes by 2 months and 58% had none by 60 months posttransplant. Logistic regression analysis revealed that a cadaver donor kidney (vs. living) (p = 0.004), a 1 to 6 antigen mismatch (vs. 0 mismatch) (p = 0.001), and CsA levels < 150 ng/ml (vs. > or = 150 ng/ml) correlated with biopsy-proven acute rejection. The correlation for CsA levels < 150 ng/ml (vs. > or = 150 ng/ml) held true for levels at 1 wk (p < 0.05), 1 month (p = 0.0001), 2 months (p = 0.01), and 3 months (p = 0.02) posttransplant. Similar correlation was found for CsA levels < 125 ng/ml (vs. > or = 125 ng/ml) and < 175 ng/ml (vs. > or = 175 ng/ml). Comparative analyses were made (by Chi-square) of acute and chronic rejection rates when recipients were divided into 3 groups by CsA level (< 125 ng/ml, > or = 125 to < 150 ng/ml, and > or 150 ng/ml). At each time point (1 wk, 2 wk, 1 month, 2 months, 3 months), CsA levels < 125 ng/ml (vs. > or = 125 to < 150 ng/ml and > or = 150 ng/ml) were associated with the greatest increased risk of acute rejection--for both cadaver and living related recipients (all p < 0.05). CsA levels < 125 ng/ml at each time point (1 wk, 2 wk, 1 month, 2 months, 3 months) were also associated with a significantly increased risk of chronic rejection (all p < 0.001). The incidence of both acute and chronic rejection was reduced in the group with CsA levels > or = 125 to < 150 ng/ml and further reduced in the > or = 150 ng/ml group. Our data indicate that maintaining CsA levels > or = 150 ng/ml as part of triple therapy reduces the incidence of both acute and chronic rejection. Because chronic rejection is the leading cause of late allograft loss, maintaining adequate CsA levels should improve long-term graft survival. Based on this analysis, we have modified our own immunosuppressive regimens to achieve higher CsA levels earlier posttransplant.

Study of accommodative facility testing reliability.

This study was designed to evaluate the reliability of the accommodative facility testing procedure. Sixty-six subjects, ages 8 to 12 years, were studied over 3 consecutive weeks. Monocular and binocular accommodative facility, using plus and minus 2 D lenses, was performed each week. Statistical analysis showed a significant mean increase in cycles per minute (cpm) between initial and subsequent testing periods, both monocular and binocular, for all subjects as a group. The most dramatic increases were observed among subjects who scored below established norms initially. To evaluate the effect of test-retest variability on the subject's pass/fail status the first test period results were used to categorize the subjects as pass or fail. Passing was greater than or equal to 11 cpm monocularly, greater than or equal to 8 cpm binocularly. Failing was less than 1, cpm monocularly, less than 8 cpm binocularly. Subsequent test results were compared to the initial testing results to determine the pass/fail reliability of the testing procedure. No significant differences were found to occur in either the monocular or binocular "pass" category. However, a significant increase in the passing rate from the initial to the subsequent testing periods for both the monocular and binocular facility rates was observed in the "fail" category. Dividing the fail group into "low-fails" (less than 6 cpm monocularly, less than 3 cpm binocularly) and "high-fails" (greater than 6 less than 11 cpm monocularly, greater than 3 less than 8 cpm binocularly) indicated this significant increase was principally in the high-fail group.