Biomedical subjects

M J Cowan

Publications and source records attributed to M J Cowan.

At least 55 records · Page 3Linked to original sources

PubMed1996

Circulating red cells usually remain of host origin after bone marrow transplantation for severe combined immunodeficiency.

BACKGROUND: Patients with severe combined immunodeficiency (SCID) treated with allogeneic bone marrow transplantation often receive a milder conditioning regimen than patients who undergo transplantation for hematologic malignancy, and they regularly retain circulating white cells of host origin. The origin of circulating red cells following successful bone marrow transplantation to treat SCID is not known. STUDY DESIGN AND METHODS: Review of the medical records identified all patients with SCID who underwent ABO-mismatched bone marrow transplantation at the University of California, San Francisco, between 1982 and 1994. The ABO and Rh phenotype at >6 months after transplantation was determined for all successful transplants by review of the medical record or the taking of a fresh blood sample for analysis. Patient-conditioning and donor bone marrow-preparative regimens were reviewed to assess their possible influence on the red cell phenotype after successful bone marrow transplantation. RESULTS: Nine of 35 SCID patients who underwent successful transplantation received marrow from ABO-mismatched donors. Eight of the nine patients had only host red cells circulating at 6 to 84 months after transplantation, while one patient had only donor red cells circulating at 48 months after transplantation. None of the patients had circulating red cells of both host and donor origin. Conditioning regimens included cyclophosphamide and antithymocyte globulin for all nine patients; only three patients also received total body irradiation. Seven of the nine patients received related-donor, HLA-mismatched bone marrow, and two patients received HLA-identical bone marrow; eight patients received T-cell-depleted bone marrow. The one patient whose red cell phenotype converted to that of the donor received T-cell-depleted, haploidentical marrow, and the preparative regimen included chemotherapy and total body irradiation. CONCLUSION: SCID patients successfully treated with allogeneic bone marrow transplantation typically fail to show circulating red cells of donor phenotype; this finding is in contrast to the universal presence of circulating donor red cells following successful bone marrow transplantation to treat hematologic malignancies and other diseases. The milder conditioning regimens typically given to patients with SCID, along with T-cell depletion and HLA mismatching, may play a role in this different outcome. It is not known whether the inability to find circulating red cells of donor origin is due to a failure to engraft donor pluripotent stem cells or a failure of engrafted donor stem cells to differentiate along the erythroid lineage.

Blood Grouping and Crossmatching↗

PubMed1996

New alleles of IGKV genes A2 and A18 suggest significant human IGKV locus polymorphism.

The human kappa light chain consists of approximately 35 potentially functional IGKV genes. However, an estimation of the diversity in the IGKV repertoire of an individual will be affected by the extent of polymorphisms for the different IGKV genes and their patterns of inheritance. To date, little information is available to indicate the extent of allelic variation of the IGKV genes. We examined the extent of allelism for one IGKV gene pair, the distal region A2 gene and its closely related proximal region duplicate A18. We found two new alleles for A2 and one new allele for A18, and sequenced approximately 1 kilobase flanking each gene. The new A18 allele, unlike the originally described allele, appears to be functional. All these alleles were found at relatively high frequencies in the four ethnic populations studied, with the exception of the defective A2b allele which was highly represented only in Navajos. The originally described A2a allele encodes for the predominant protective antibody against Haemophilus influenzae. Therefore, the patterns of allelic inheritance described for this IGKV gene pair indicate that allelism in the IGKV locus is likely to have a significant impact on immune responses.

Alleles↗

PubMed1996

Bone marrow 'boosts' following T cell-depleted haploidentical bone marrow transplantation.

Nine patients transplanted for non-malignant conditions (eight severe combined immunodeficiency, one aplastic anemia) received lectin-treated T cell-depleted BMTs from haploidentical donors. Each patient subsequently received a second T cell-depleted transplant (¿boost') from the same donor, without conditioning, because of a delay in the recovery of T cell immunity associated with evidence of engraftment. The median time to boost after initial BMT was 0.5 years (range 0.2-4.6 years). No conditioning therapy was used prior to the boost (except one patient who received ATG) and no GVHD prophylaxis was used during either the initial or subsequent BMTs. Eight of the nine patients are surviving at a median follow-up of 2.9 years (range 0.3-6.2 years). Following BMT boost, T cell function improved with the lymphocyte proliferative responses to PHA, PWM and alloantigen all increasing at least eight-fold. The mean percentage of CD3+ lymphocytes increased from 20 +/- 7% of total lymphocytes following the first BMT to 66 +/- 7% following the marrow boost (P < 0.001). This increase was generated primarily by an increase in the CD4+ lymphocyte subset which increased from 13 +/- 3% post-transplant to 44 +/- 6% after the BMT boost (P < 0.005), and was reflected in both the CD4+/Leu8+ and CD4+/Leu8- lymphocyte populations. Measurements of B cell immunity (immunoglobulins, isohemagglutinins and B cells) showed no significant effect of the marrow boosts. These results suggest that bone marrow 'boosts' are an effective means for improving T cell immunity in patients who fail to recover adequate immune function after T cell-depleted bone marrow transplantation and may be applicable as immunotherapy following allogeneic BMT undertaken to treat malignancy.

Anemia, Aplastic↗

PubMed1996

Long-term engraftment following in utero T cell-depleted parental marrow transplantation into fetal rhesus monkeys.

A major concern with allogeneic BMT for treating most inherited diseases is the need to overcome graft rejection with conditioning chemotherapy which is associated with a relatively high morbidity and mortality. This can be eliminated if the transplant is done in utero when the fetus is unable to reject donor hematopoietic stem cells (HSC). We studied the efficacy of T cell-depleted (TCD) parental bone marrow as a source of HSC for transplantation into early gestation non-defective fetal rhesus monkeys. Thirteen opposite sexed TCD transplants were done into 44 day fetal recipients and 12 into 61 day recipients (165 day total gestation). The procedure-related mortality was 8%, all in the earlier age group. The overall survival was 60% at birth with a projected survival of 44 +/- 10% at 1.5 years with no difference between the two age groups. We used a PCR assay for the rhesus Y chromosome to detect male donor cells in female recipients (six animals transplanted at 44 days and five at 63 days). The overall engraftment rate was 73% with no difference as a function of gestational age at transplant. In six long-term surviving engrafted females we detected donor cells in the peripheral blood and bone marrow up to 3 years of age. We found a delay in the appearance of donor cells in the peripheral blood in engrafted animals, in some cases for up to 6 months post-BMT. In vitro mixed lymphocyte reaction and cell-mediated lymphocytotoxicity studies between the recipient and donor cells indicate that tolerance was induced to donor cells. Individual and pooled erythroid and myeloid marrow colonies grown in methyl cellulose were collected and analyzed for donor origin by PCR. The amount of donor cells in marrows from long-term engrafted animals was < 0.1%. In a fetal recipient studied at 35 days post-BMT, donor cells were detected in bone marrow and liver in both erythroid and myeloid lineages. These results indicate that TCD parental marrow can durably engraft in utero. While the engraftment rate is similar to that seen with fetal liver as the source of HSC, the degree of peripheral blood engraftment (percent donor cells) in this non-defective primate model is low. It will require increasing the percent pre-or postnatally for this approach to be clinically relevant in those disorders in which there is no selective survival advantage for normal engrafted donor cells.

Animals↗

PubMed1996

Haploidentical bone marrow transplants for two patients with reticular dysgenesis.

We report two cases of reticular dysgenesis (RD) successfully treated by BMT utilizing T cell-depleted haploidentical marrow grafts. One child failed to engraft after conditioning with ATG, and the other failed two transplant attempts with cyclophosphamide + ATG, and busulfan + cyclophosphamide + ATG, respectively. Donor engraftment was achieved in both patients following treatment with 700 cGy TBI, with or without other agents. These results, taken together with previous reports in the literature, suggest that children with RD may require more intensive conditioning than patients with other types of severe combined immunodeficiency syndrome.

Agranulocytosis↗

PubMed1995

Induction of tolerance in nondefective mice after in utero transplantation of major histocompatibility complex-mismatched fetal hematopoietic stem cells.

Significant morbidity and mortality are associated with the conditioning therapy needed for postnatal bone marrow transplantation (BMT) for inherited diseases. This could be eliminated with hematopoietic stem cell (HSC) transplantation in utero, when the immunoincompetence of the fetus permits engraftment without the need for immunosuppressive therapy. We have established an in utero (day 11 to day 13) model of HSC transplantation in nondefective, allogeneic major histocompatibility complex (MHC)-mismatched mice. Donor cells wre from pooled fetal livers of C57BL/6 (H-2b, GPI-1b) mice. Engraftment was tested by quantitative polymerase chain reaction (PCR) for the Y chromosome in female recipients (with 0.00001% sensitivity). Eight percent (3 of 36) of allogeneic mismatched (Balb-c, H-2d) recipients and 25% (3 of 12) of congenic (C57B1/6, GPI-1a) recipients showed durable engraftment (male donor cells detected beyond 20 weeks of age) based on analysis of peripheral blood leukocytes (P > .08). When spleen and liver were analyzed, 51% (17 of 33) of allogeneic recipients and 50% (6 of 12) of congenic recipients showed durable engraftment (P > .3). The percent donor cells that durably engrafted varied from as low as 0.0001% in spleen and liver to as high as 0.6% in peripheral blood. Postnatal boosting with a single dose of allogeneic MHC-mismatched donor cells in a tolerant, engrafted mouse resulted in a significant increase in donor cells in the peripheral blood from 0.2% pre-boost to 5% 6 months after the boost. There was no evidence of engraftment in nontolerant mice after the postnatal boost with a similar dose of donor cells. Twenty-two allogeneic recipients were evaluated for donor skin graft acceptance at 6 to 12 months of age. Three mice with engraftment in blood and/or tissue permanently accepted donor skin grafts, one of them with donor cells detectable only in the liver. Six additional mice that showed prolonged skin graft acceptance had no evidence of durable engraftment in the blood but were engrafted in the liver and/or spleen. The degree of engraftment in tolerant mice was low (< or = 0.1% donor cells). We conclude that at an early gestational age in nondefective mice (1) high rates of durable engraftment are achievable, although the degree of engraftment is usually low (less than 1%); (2) the percent of donor cells in the peripheral blood may be increased by a postnatal boost of donor cells in tolerant animals without conditioning therapy; (3) MHC appears to have little influence on engraftment efficiency at an early gestational age; (4) a very small number of circulating donor cells in the blood or the tissues is sufficient for the induction and maintenance of tolerance, and (5) the presence of donor cells in the circulating blood is not necessary for prolonged skin graft acceptance or maintenance of permanent skin graft acceptance.

Animals↗

PubMed1995

Severe combined immunodeficiency with absence of peripheral blood CD8+ T cells due to ZAP-70 deficiency.

During ontogeny, T lymphocytes are selected for CD4 or CD8 expression in part by their ability to signal properly through the TCR. Transmission of such signals requires the activation of specific cytoplasmic protein tyrosine kinases (PTKs) which lead to T-cell activation through poorly understood mechanisms. Recently, mutations in one such PTK, called ZAP-70, have been shown to be responsible for a rare, autosomal recessive form of severe combined immunodeficiency (SCID) in humans. This distinctive SCID syndrome is characterized by the selective absence of peripheral CD8+ T cells and by abundant circulating CD4+ T cells that fail to respond to TCR-mediated stimuli in vitro. In this report, we describe in detail the clinical and laboratory findings in one patient with ZAP-70 deficiency and discuss the insights provided by this disorder into the pathways of TCR signal transduction and T-cell development.

B-Lymphocytes↗

PubMed1995

Measurement of heart rate variability.

Heart rate variability (HRV) is a measure of autonomic nervous system balance/imbalance. Measurement and analysis of HRV can be classified into time domain analysis and frequency domain analysis. Time domain analysis is a general measure of autonomic nervous system balance and is based on altered versions of the measurement of the standard deviation of heart period, defined in terms of the sinus R-R intervals over time. There are six commonly used time domain measurements: SDANN, 24-hr SD, SD, RMSSD, RR50, and % RR50. Frequency domain analysis uses either autoregressive or fast Fourier transform techniques to delineate parasympathetic (high-frequency components) from sympathetic (low-frequency components) of autonomic control. This study explores the clinical applications of HRV with respect to respiratory sinus arrhythmia, exercise, mortality, sudden cardiac arrest, myocardial infarction, and congestive heart failure.

Autonomic Nervous System↗

PubMed1994

Anti-tetanus toxoid antibody production after mismatched T cell-depleted bone marrow transplantation.

We explored B-cell function after tetanus toxoid (TT) immunization in 12 children with severe combined immunodeficiency disease or leukemia who were long-term survivors of an HLA-matched sibling or haplocompatible T cell-depleted parental bone marrow transplant (BMT), 10 of their healthy donors, and 13 normal controls. Specific in vivo and in vitro anti-TT antibody (Ab) production were measured by ELISA. We studied donors' and recipients' peripheral blood mononuclear cells (PBMC) and mixed E- (non-T cells) and E+ cells (T cells) spontaneously and after stimulation by TT in the absence or presence of interleukin-2 (IL-2), IL-4, and IL-6. Five of the 12 patients and all donors and controls responded with in vivo anti-TT Ab. In vitro anti-TT Ab production correlated with the in vivo response. All seven of the nonresponders were either fully engrafted or mixed chimeras (donor T cells but autologous B cells and monocytes). We could not identify a T-cell defect in four of the five nonresponders who were tested. In contrast, E- cells from three of three responders cooperated with fresh donor E+ cells even when they shared only one HLA haplotype. In three of seven nonresponders, in vitro anti-TT Ab production was restored after the addition of IL-4 or IL-6 but not IL-2. Our results suggest that the humoral immunodeficiency that exists post mismatched T cell-depleted BMT is either a B-cell, a monocyte, or a B-cell/T-cell cooperation defect which, in some patients, may be correctible with the addition of a cytokine. Also, it is not necessary to engraft donor B cells to achieve normal antibody responses and the ability to respond does not appear to correlate with pretransplant chemotherapy.

Adolescent↗

PubMed1994

Effects of gender and age on heart rate variability in healthy individuals and in persons after sudden cardiac arrest.

The purpose of this study was to describe the effects of gender and age on heart rate variability (HRV) in healthy volunteers (n = 111; 40 men and 71 women) and in persons after sudden cardiac arrest (SCA) (n = 95; 79 men and 16 women). Frequency-domain measurements and six time-domain measurements of HRV (SDANN, 24-hour SD, SD, RMSSD, RR50, and %RR50) were taken. Two-factor analysis of variance was performed. In general, HRV was significantly lower in healthy women compared with healthy men in all the time-domain and frequency-domain variables except for the high-frequency components, RMSSD, RR50, and %RR50. There were no significant gender differences in the SCA sample. All the time-domain and frequency-domain measurements decreased with age in the healthy sample, but only the frequency-domain measurements decreased with age in the SCA sample.

Aged↗

PubMed1994

In utero hematopoietic stem cell transplants for inherited diseases.

PURPOSE: The treatment of choice for many inherited diseases is bone marrow transplantation (BMT). Limitations to using marrow transplants for inherited diseases include (a) the toxicity associated with high doses of chemotherapy necessary to obtain engraftment; (b) the complications associated with graft-versus-host disease (GVHD); (c) the fact that only 20-25% of children will have a human leukocyte antigen (HLA)-matched donor; and (d) the concern that, at least for some inherited diseases, significant organ damage, especially to the nervous system, has occurred by the time the child is diagnosed and evaluated for possible BMT. In utero transplantation of hematopoietic stem cells (HSCs) offers the possibility of overcoming many of these limitations. PATIENTS AND METHODS: One of the biggest hurdles to a successful transplant is the ability of the recipient to reject the donor marrow. Except in patients with severe combined immunodeficiency disease (SCID), overcoming this hurdle requires high doses of chemotherapy. Early in gestation, the fetus is significantly immunoincompetent. Before 14-15 weeks of gestation, the human fetus appears to be similar to a child with SCID in its inability to reject allogeneic cells. Potential sources for HSCs are HLA-matched sibling marrow, fetal liver, parental bone marrow, and cord blood. RESULTS: With fetal liver, only cells from fetuses < 10-12 weeks are acceptable because of the high risk of GVHD. With parental marrow, the cells must be T cell depleted in order to minimize the risk for GVHD. Problems in using fetal liver include the inability to obtain sufficient numbers of cells and inadequate supplies of donor tissue. The source and supply of parental bone marrow is almost unlimited, but, because of the need for T-cell depletion, bone marrow from a parent may have a lower engraftment rate in the child. CONCLUSIONS: Studies in fetal murine and Rhesus models using fetal liver or T cell-depleted bone marrow from adult animals suggest that engraftment can be successfully obtained, providing the transplant is performed sufficiently early in gestation. To date, at least a dozen in utero human transplants have been attempted worldwide in fetuses diagnosed with a variety of inherited diseases. Because of the small number of transplanted fetuses and the variety of diseases and differing transplant conditions, it is difficult to draw any firm conclusions regarding ultimate efficacy of the procedure and its risk. However, it does appear that the age of gestation of the recipient, the dose of cells infused, and possibly the route of administration of the HSCs will be critical factors in determining success rates for this approach. The successful application of in utero transplantation would allow treatment of a variety of inherited diseases early in gestation while eliminating many of the risks associated with conventional BMT.

Animals↗

PubMed1993

Immune reconstitution in severe combined immunodeficiency disease after lectin-treated, T-cell-depleted haplocompatible bone marrow transplantation.

We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post-BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus-host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post-BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor.

B-Lymphocytes↗

PubMed1993

Integration of biological and nursing sciences: a 10-year plan to enhance research and training.

A proposed multiyear plan of funding mechanisms by the National Center for Nursing Research (NCNR) to increase the use of biological theory and measurements in nursing research has been developed for both research training and research programs. The objectives of the research training programs are (a) to develop a cadre of nurse scientists with solid research training in the biological sciences, (b) to upgrade to state-of-the-art biological research for mid-career nurse scientists, and (c) to ensure adequate highly trained biological-nurse manpower will be available to accomplish the nation's nursing research agenda. The objectives of the research programs are (a) to stimulate nurse scientists to undertake novel, innovative research using state-of-the-art biological technology, (b) to link the behavioral and biological underpinnings of nursing science in specified areas of biomedical clinical research, and (c) to ensure that, in the coming decade, nursing science and behavioral research will be inextricably interwoven with biological research. The research training programs include: targeted predoctoral-postdoctoral transitional training, targeted predoctoral or postdoctoral fellowships, training awards for existing institutional training grants in other disciplines, mid-career awards, the Nurse Scientist award, and institutional training grants for biological nursing. The research programs include: small grants programs, augmentation of existing projects in other Institutes, Requests For Applications (RFA) in biobehavioral nursing, cluster studies, and clinical trials.

Awards and Prizes↗

PubMed1993

Description of time- and frequency- domain-based measures of heart rate variability in individuals taking antiarrhythmics, beta blockers, calcium channel blockers, and/or antihypertensive drugs after sudden cardiac arrest.

Concomitant drug therapies after sudden cardiac arrest and their potential effect of altering heart rate variability (HRV) represent confounding factors in interpreting the outcome of nonpharmacologic therapies on HRV. The purpose of this study is to describe a broad spectrum of time-domain and frequency-domain measurements of HRV in 50 individuals after sudden cardiac arrest. Some of the individuals were taking antiarrhythmics (n = 9), beta blockers (n = 13), calcium channel blockers (n = 10), nitrates (n = 8), cardiac glycosides (n = 10), and/or antihypertensives (n = 12). Heart rate variability was measured using a Holter recorder for 24 hours and the SpaceLabs FT2000 Monitoring System (Redmond, WA). In those individuals taking antiarrhythmic drugs, the power density within the low-frequency range (.016-.04 Hz) was significantly decreased (P = .001) compared to those not taking antiarrhythmics (n = 41). However, 78% of the people taking antiarrhythmics also had congestive heart failure (New York Heart Association functional classes II and III), which also decreased HRV. Those individuals taking beta blockers tended to have slower heart rates (P < .01). The association between beta blocker use and HRV was positive, but not statistically significant except for the increased power density in the low-frequency range (P < .05). In general, the relationships between HRV and drug therapy--calcium channel blockers, antihypertensives, cardiac glycosides, or nitrates--were not statistically significant.

Adrenergic beta-Antagonists↗

PubMed1993

Development of tolerance after haplocompatible T-depleted bone marrow transplantation.

We evaluated proliferative responses in mixed lymphocyte cultures (MLC) following bone marrow transplantation (BMT) in 14 recipients of T cell-depleted haplo-compatible parental marrow: 11 for the treatment of severe combined immunodeficiency (SCID), 2 for leukemia and 1 for Wiskott-Aldrich syndrome (WAS). We compared the results obtained in 9 SCID patients and 1 WAS patient with split chimerism (T cells of donor origin, B cells and monocytes of recipient origin) to 4 patients (2 SCID and 2 leukemias) who were full chimeras (T, B and monocytes of donor origin). In the full chimeras, as with the fresh donor PBMC, fresh donor T cells did not proliferate in the MLC to recipient non-T cells (E-). In this group there were no differences (p > 0.2) between the responses of engrafted T and fresh donor T to recipient E- cells. We found tolerance of engrafted donor T cells to residual mismatched T cell-depleted (E-) recipient cells in the split chimera group. In this group the engrafted T cells had low or no responses in MLC to HLA mismatched E- host cells compared with fresh donor cells (p < 0.001). In 3 of 8 split chimera patients that we tested the addition of small numbers (5000-10,000) of freshly isolated donor T cells, irradiated or not, resulted in a two fold increase in the engrafted T cell response to recipient E- cells. In contrast, in 3 of 3 full chimeras tested, the addition of fresh donor T cells had no demonstrable effect on the response of engrafted T cells to recipient E-.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Prenatal diagnosis of Chediak-Higashi syndrome.

We report the first prenatal diagnosis of an affected fetus with Chediak-Higashi syndrome (CHS). Diagnosis was accomplished via fetal blood sampling at 17 menstrual weeks and was confirmed after birth. Retrospective measurement of the largest acid phosphatase-positive lysosomes in cultured amniotic fluid cells and chorionic villus cells showed that in CHS these lysosomes are significantly larger than those in normal cells. This method may be used for prenatal diagnosis of CHS by amniocentesis and chorionic villus sampling (CVS).

Acid Phosphatase↗

PubMed1992

Autoregressive spectral models of heart rate variability. Practical issues.

Autoregressive time series model-based spectral estimates of heart period sequences can provide a parsimonious and visually attractive representation of the dynamics of interbeat intervals. While a corollary to Wold's decomposition theorem implies that the discrete Fourier periodogram spectral estimate and the autoregressive spectral estimate converge asymptotically, there are practical differences between the two approaches when applied to short blocks of data. Autoregressive spectra can achieve good frequency resolution and excellent statistical stability on short segments of heart period data of sinus origin. However, the order of the autoregressive model (number of free parameters to be estimated) must be explicitly chosen, a decision that influences the trade-off of frequency resolution with statistical stability. Akaike's Information Criterion (AIC), an information-theoretic rule for picking the optimum order, is sensitive to the aggregate amount of data in the analysis. Thus, the best model order for estimating the spectrum of a 4-minute segment of data will generally be lower than the best order for estimating an hourly spectrum based on averaging 15 4-minute spectra. A major advantage of the autoregressive model approach to spectral analysis is the ease with which it can be extended to handle messy data frequently seen in heart rate variability studies. A number of autoregressive-based robust-resistant techniques are available for the analysis of heart period sequences that contain a high volume of nonsinus and other unusual beats intervals. A theoretically satisfying framework is also available for spectral analysis of unevenly sampled data and missing data.

Fourier Analysis↗

PubMed1992

Comparison of autoregression and fast Fourier transform techniques for power spectral analysis of heart period variability of persons with sudden cardiac arrest before and after therapy to increase heart period variability.

Clinical studies have used two types of analysis of the power spectral estimates of heart period variability: autoregressive and fast Fourier transform techniques. Controversy exists regarding which method is the most valid. The specific aims of this study are: (1) to describe the power spectra of heart period variability before and after an intervention designed to increase heart period variability in persons after sudden cardiac arrest; (2) to compare the integral of power spectral density between autoregressive and fast Fourier transform techniques within low and high-frequency bands; (3) to compare the magnitude of the spectral peak values determined by autoregressive and fast Fourier transform techniques approaches within low and high-frequency bands; and (4) to compare the aforementioned parameters using 4-minute, 1-hour, and 24-hour blocks of heart period data. Results indicated high correlations between spectral estimations by autoregressive and fast Fourier transform techniques using integrals or peak values within either the low or high-frequency ranges. The autoregressive technique demonstrated better resolution of sharp peaks than the fast Fourier transform technique, and makes a smoother, more interpretable curve. Lastly, people can cognitively change their heart rate variability.

Biofeedback, Psychology↗