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Biomedical subjects

M Snell

Publications and source records attributed to M Snell.

14 recordsLinked to original sources
PubMed2006

Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation.

While immune hemolysis due to donor isohemagglutinin (IH) production often complicates minor ABO incompatible peripheral blood hematopoietic stem cell transplantation (PBSCT), it is not known if this occurs with umbilical cord blood transplantation (UCBT). We compared IH production and hemolysis following minor ABO allogeneic PBSCT and UCBT. We reviewed 24 ABO minor incompatible allogeneic PBSCTs and 14 ABO minor incompatible UCBTs. Patients were evaluated for donor-derived IH by reverse ABO grouping. Evaluation of hemolysis was based on clinical and laboratory findings of anemia associated with increased RBC transfusion need, concomitant with the appearance of donor-derived IH. Of the 24 ABO minor incompatible allogeneic PBSCTs, 15 produced donor-derived IH from 6 to 88 days following transplantation, with seven of 15 patients exhibiting clinically evident hemolysis. There was no significant difference in days to leukocyte engraftment or infused CD34 cells in patients with or without donor-derived IH. None of the 14 patients receiving ABO incompatible UCBTs showed evidence of donor-derived IH following transplantation with a median follow-up of 60 days. We conclude that donor IHs are not produced in patients undergoing minor ABO incompatible UCBTs suggesting fundamental immunologic differences between allogeneic PBSCT and UCBT.

Adolescent↗
PubMed1998

Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control.

BACKGROUND: Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). METHODS AND RESULTS: In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75 degrees tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LFSAP). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index alpha, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, MSNA, LF/HF, and LFSAP were higher in COI patients, whereas BP and CVP were similar in the two groups. During tilt, BP did not change and CVP fell by the same extent in the 2 groups; the increase of HR and LF/HF was more pronounced in COI patients. Conversely, the increase of MSNA was lower in COI than in control subjects. Baroreflex sensitivity was similar in COI and control subjects at rest; tilt reduced alpha similarly in both groups. CONCLUSIONS: COI is characterized by an overall enhancement of noradrenergic tone at rest and by a blunted postganglionic sympathetic response to standing, with a compensatory cardiac sympathetic overactivity. Baroreflex mechanisms maintain their functional responsiveness. These data suggest that in COI, the functional distribution of central sympathetic tone to the heart and vasculature is abnormal.

Adult↗
PubMed1998

Yohimbine in neurally mediated syncope. Pathophysiological implications.

In this study, we evaluated if increased sympathetic stimulation is an essential requirement for the development of neurally mediated syncope (NMS) by manipulating overall sympathetic outflow in subjects susceptible to tilt-induced syncope. Eight previously characterized patients with recurrent NMS (five females and three males; 34+/-2 yr) were recruited from the Vanderbilt Syncope Unit and eight age-matched controls underwent initial administration of clonidine (CLO) or yohimbine (YHO). This was done, prospectively, to determine doses of these agents that would increase or decrease plasma norepinephrine levels by >/= 30%. On a different day, in all subjects we determined intraarterial blood pressure, EKG and muscle sympathetic nerve activity (MSNA) both supine and during upright tilt. After this, subjects randomly received either CLO or YHO, and 3 h later another tilt was performed. After 1 wk, a similar procedure with the other drug was performed. During the two basal tilts, all the control subjects completed the study, whereas all the NMS patients developed syncope. Reduction in sympathetic tone by CLO resulted in a decreased tolerance to tilt in three out of eight controls and in all the NMS patients. In contrast, YHO not only increased basal plasma NorEpi levels and MSNA, but also prevented syncope in seven out of eight patients. In a selected population of patients, increased sympathetic activity is not a prerequisite for the development of syncope. Yohimbine-induced enhancement of sympathetic tone in patients with NMS improves orthostatic tolerance and raises the possibility that this drug may be a useful agent in the treatment of NMS.

Adult↗
PubMed1997

Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt.

The pathophysiology of neurally mediated syncope is poorly understood. It has been widely assumed that excessive sympathetic activation in a setting of left ventricular hypovolemia stimulates ventricular afferents that trigger hypotension and bradycardia. We tested this hypothesis by determining if excessive sympathetic activation precedes development of neurally mediated syncope, and if this correlates with alterations in baroreflex function. We studied the changes in intraarterial blood pressure (BP), heart rate (HR), central venous pressure (CVP), muscle sympathetic nerve activity (MSNA), and plasma catecholamines evoked by upright tilt in recurrent neurally mediated syncope patients (SYN, 5+/-1 episodes/mo, n = 14), age- and sex-matched controls (CON, n = 23), and in healthy subjects who consistently experienced syncope during tilt (FS+, n = 20). Baroreflex responses were evaluated from changes in HR, BP, and MSNA that were obtained after infusions of phenylephrine and sodium nitroprusside. Compared to CON, patients with SYN had blunted increases in MSNA at low tilt levels, followed by a progressive decrease and ultimately complete disappearance of MSNA with syncope. SYN patients also had attenuation of norepinephrine increases and lower baroreflex slope sensitivity, both during tilt and after pharmacologic testing. FS+ subjects had the largest decrease in CVP with tilt and had significant increases in MSNA and heart rate baroreflex slopes. These data challenge the view that excessive generalized sympathetic activation is the precursor of the hemodynamic abnormality underlying recurrent neurally mediated syncope.

Adult↗
PubMed1997

Modeling of arterial and cardiopulmonary baroreflex control of heart rate.

We evaluated R-R interval changes (delta R-R interval) in 13 subjects (27 +/- 6 yr; 7 men and 6 women) as a function of blood pressure changes at the carotid sinus and aortic arch and central venous pressure changes at the cardiopulmonary receptors. Neck chamber pressure and suction were used to change pressure at the carotid sinus while lower body negative pressure, phenylephrine infusion, and nitroprusside infusion were used to change pressure at the carotid sinus (delta CSP), aortic arch (delta AAP), and cardiopulmonary receptors (delta CPP). Random effects regression analysis showed a significant linear relationship for delta R-R interval (-1.75 + 1.64 delta CSP + 15.40 delta AAP + 29.02 delta CPP + error), and the correlation (r) between the observed and predicted delta R-R interval was 0.82 (P < 0.00001). Sixty-seven percent of the delta R-R interval variability observed in the study is explained by the model. delta AAP accounts for approximately 63%, delta CSP for 14%, and delta CPP for 23% of the explained delta R-R interval.

Adult↗
PubMed1994

Calcium metabolism following renal transplantation.

Abnormalities of calcium homeostasis are a recognized feature of end-stage renal disease. The treatment of choice is renal transplantation, but this does not always result in normalization of the biochemical profile. Persistent hypercalcaemia is well documented and our study was undertaken to investigate the status of the calcium regulating hormones in renal patients post-transplantation. Serum calcium, parathyroid hormone, 1,25-dihydroxyvitamin D (1,25(OH)2D) and osteocalcin concentrations were measured in post-transplant patients. Twenty per cent of the patients had subnormal 1,25(OH)2D concentrations while 55% had biochemical evidence of hyperparathyroidism but only 5% were hypercalcaemic. Time elapsed since transplantation was not correlated with any of the analytes investigated and there was no relationship between persistent impairment of renal function and abnormalities of calcium homeostasis.

Adult↗
PubMed1986

Increasing kidney transplantation in Britain: the importance of donor cards, public opinion and medical practice.

The Department of Health and Social Security has recently spent over three-quarters of a million pounds advertising the merits of kidney donor cards. The advertising campaign stresses that carrying signed cards requesting the removal of kidneys and other organs after death both increases the number of kidneys available and increases the number of kidney transplants that actually take place. This paper examines the relative success of the kidney donor card campaign in Britain and the nature of the relationship between a more widespread distribution of donor cards and the frequency of kidney transplantation. This is done in two main ways: Through a review of the evidence detailing public support expressed in the media and from social surveys (including original empirical work conducted at Bath University). By an analysis of previously unpublished statistical evidence made available by the Department of Health and Social Security. The paper concludes that the battle for public sympathy towards kidney donation has largely been won and the kidney donor card campaign has been a success. However these success perhaps deflect attention away from more important issues in the transplant equation, as the link between card carrying and increased transplantation is neither direct nor simple.

Advertising↗
PubMed1982

Effect of albumin binding on the hepatic transport of rose bengal: surface-mediated dissociation of limited capacity.

We have studied the steady-state removal of rose bengal by perfused rat livers to decide whether the tight association of this anion with albumin is consistent with the conventional view that only the free fraction in the sinusoidal lumen is available for hepatic transport. The results show that the concentration of free dye is not nearly high enough to account for the observed removal rate. From these observations we argue that the liver cell surface reduces the affinity of rose bengal for albumin by a factor of approximately 100 below that observed in free solution. The findings extend and refine the results of a similar experiment with taurocholate we reported previously and they confirm the suggestion by others that the dissociation mechanism displays saturation kinetics as the albumin concentration increases.

Animals↗
PubMed1979

Subcutaneous Corynebacterium parvum in bladder cancer: a controlled study of its immunological effects.

Fourteen out of 26 patients with invasive bladder cancer were randomly assigned to receive weekly subcutaneous injections of Corynebacterium parvum (CP) in addition to standard treatment. Peripheral blood T lymphocyte percentage, K cell activity, mitogen responsiveness, and monocyte and polymorph leucotaxis were measured at intervals over a period of 1 to 2 years. The only consistent difference between the CP-treatment patients and the controls was a slightly higher level of K cell activity in the former, who, however, fared rather worse than the controls in terms of survival.

Cell Survival↗