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Biomedical subjects

F B Axelrod

Publications and source records attributed to F B Axelrod.

At least 55 records · Page 3Linked to original sources
PubMed1995

Blood center perspective: defining the ideal platelet concentrate.

During the past two decades, an increased demand for platelets has challenged blood collection centers to produce a safe and readily available supply. Defining the ideal platelet for transfusion is a process that cannot be decided by a single entity. Collection centers are only one member of a partnership which involves the donor, transfusion service, hospital administration, clinicians, and patients. Regulatory definitions exist to help guide collection centers to the minimum acceptable criteria for the production of platelets, but in reality, the standard by which clinicians judge the efficacy of the product is most important.

Blood Banks↗
PubMed1994

Atrial natriuretic peptide response to postural change and medication in familial dysautonomia.

Circulating atrial natriuretic peptide (ANP) was assayed before and after postural change and exercise in 54 patients with familial dysautonomia (FD) and 20 controls. ANP levels were compared with blood pressure, heart rate, plasma catecholamines and parameters of renal function. Compared with controls supine FD subjects had elevated blood pressures, heart rates and ANP levels (39 +/- 4 pg/ml vs. 23 +/- 3 pg/ml, p < 0.01). With the erect posture and exercise in FD subjects, blood pressure fell below control values, with ANP lowered. In FD subjects, blood pressure was correlated with ANP levels when supine and when erect and with heart rate post exercise. In controls, ANP levels did not correlate with other parameters. In FD patients on metoclopramide, supine and erect blood pressure and ANP levels were higher. FD subjects treated with fludrocortisone, had elevated supine and erect noradrenaline (p < 0.05 and p = 0.06); and those on diazepam had lower erect and post exercise noradrenaline (p < 0.05), but ANP levels were similar. In conclusion, sympathetic denervation may increase FD patients' responsiveness to other regulators of cardiovascular integrity, such as ANP. In addition, circulating ANP and catecholamines in FD subjects appear to be influenced by commonly used medications, such as metoclopramide.

Adolescent↗
PubMed1993

The effects of postural change and exercise on renal haemodynamics in familial dysautonomia.

Cardiovascular instability is a prominent manifestation of familial dysautonomia [FD] while renal insufficiency occurs in a large number of adult FD patients. To determine if there was a causative relationship, renal artery blood flow velocity using Doppler technology, was recorded and the ratio of the peak systolic velocity (point A) to the end diastolic velocity (point B) was calculated. The A/B ratio was assessed in response to change of position and exercise, and was correlated with renal function, heart rate and systemic blood pressure. Studies were performed in 54 FD patients with a mean age of 24 years +/- 9.8 years, and 20 controls, with a mean age of 24.7 +/- 7.6 years. In the supine position, the mean A/B ratios were not significantly different, but FD subjects had a significantly higher mean blood pressure and heart rate than controls. When erect and post exercise, the mean A/B ratios in FD subjects were significantly higher than controls, p = 0.0004 and p = 0.0001, respectively. In contrast to controls, when FD subjects were standing erect and post exercise, mean blood pressure decreased significantly without a significant change in heart rate. When FD subjects were divided into two groups based on their creatinine clearance value, the group with the lower creatinine clearances had a significantly greater fall in diastolic pressure when they moved from the supine to the erect position. Our results indicate that noninvasive Doppler techniques are helpful in detecting changes in renal blood flow in subjects with familial dysautonomia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Abnormalities of the corrected QT interval in familial dysautonomia: an indicator of autonomic dysfunction.

We report abnormalities in corrected QT intervals with changes in position and after exercise in patients with familial dysautonomia and confirm the previously reported finding of abnormal heart rate and blood pressure responses. Prolonged corrected QT intervals (> 440 msec) with lack of appropriate shortening with exercise is a noninvasive means of demonstrating an aberration in autonomic regulation of cardiac conduction.

Adult↗
PubMed1993

Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis.

Familial dysautonomia (DYS), the Riley-Day syndrome, is an autosomal recessive disorder characterized by developmental loss of neurons from the sensory and autonomic nervous system. It is limited to the Ashkenazi Jewish population, where the carrier frequency is 1 in 30. We have mapped the DYS gene to chromosome 9q31-q33 by linkage with ten DNA markers in 26 families. The maximum lod score of 21.1 with no recombinants was achieved with D9S58. This marker also showed strong linkage disequilibrium with DYS, with one allele present on 73% of affected chromosomes compared to 5.4% of controls (chi 2 = 3142, 15 d.f. p < 0.0001). D9S53 and D9S105 represent the closest flanking markers for the disease gene. This localization will permit prenatal diagnosis of DYS in affected families and aid the isolation of the disease gene.

Alleles↗
PubMed1993

Exclusion of familial dysautonomia from more than 60% of the genome.

Familial dysautonomia (FD) is a recessive neurological disorder that affects the development of the sensory and autonomic nervous system. The gene defect appears to be limited to the Ashkenazi Jewish population, where the carrier frequency is 1 in 30. One hundred and ninety-one marker loci representing all autosomes were tested for linkage with the FD genetic defect in 23 families. A combination of pairwise and multipoint analyses excluded the FD gene from at least 60% of the autosomal genome. The program EXCLUDE predicted regions of chromosomes 2, 4, 5q, 9, or 10 as the most promising locations for future analyses.

Chromosome Mapping↗
PubMed1992

Respiratory system stability and abnormal carbon dioxide homeostasis.

We have tested the hypothesis that interactions among eight parameters of the respiratory and cardiovascular systems that determine the loop gain (LG) of the respiratory CO2 feedback control system might account for the degree of stability or instability of breathing patterns in healthy sleeping volunteers as well as in familial dysautonomia (FD) and congenital central hypoventilation syndrome (CCHS) patients. The predictability of cycle duration was tested as well. We measured the values of CO2 sensitivity, CO2 delivery capacity in the circulation, circulation delay, mean lung volume for CO2, and mixed venous PCO2 in 8 FD patients, 2 CCHS patients, and 19 healthy controls. The values of these parameters were used in a mathematical model to compute the LG of the respiratory control system during sleep for each epoch of respiration analyzed. The strength of the ventilatory oscillations (R) was quantified using power density spectra of the ventilation time series. All subjects were studied at inspiratory O2 concentrations (FIO2) of 0.21 and 0.15; CCHS patients and controls were also studied at 0.12 FIO2 to examine the effect of steady-state hypoxia on respiratory system stability. In 2 FD patients, LG was elevated at both levels of FIO2 and periodic breathing was observed; the values of R were elevated. Elevated mixed venous PCO2 and reduced CO2 delivery capacity were chiefly responsible for the abnormally high LG observed. In three healthy volunteers, high LG and unstable patterns were associated with high chemosensitivity. The CCHS patients, however, remained stable even at 0.12 FIO2 because LG remained equivalent to zero due to a lack of chemosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Fundoplication and gastrostomy in familial dysautonomia.

Fundoplication with gastrostomy has become a frequent treatment for patients with familial dysautonomia, so we evaluated the use of both procedures in 65 patients. Although patients differed widely in presenting signs and age, from 5 weeks to 40 years, gastroesophageal reflux was documented in 95% of patients by cineradiography or pH monitoring. Panendoscopy was a useful adjunct. Preoperative symptoms of gastroesophageal reflux included vomiting, respiratory infections, and exaggerated autonomic dysfunction. Severe oropharyngeal incoordination frequently coexisted and resulted in misdirected swallows with aspiration, dependence on gavage feedings, or poor weight gain and dehydration. Follow-up after surgical correction ranged from 3 months to 11 years; 55 patients (85%) were available for a 1-year postoperative assessment. We had no instances of surgical death. The long-term mortality rate was 14%, primarily related to severe preexisting respiratory disease. Beyond the first postoperative year, 30 patients had pneumonia attributed to continued aspiration, exacerbation of preexisting lung disease, or recurrence of gastroesophageal reflux. Of 11 patients who vomited postoperatively, six had recurrence of reflux. Recurrence of gastroesophageal reflux was documented in eight patients (12%), and we revised the fundoplication in three patients. The number of patients with cyclic crises was reduced from 18 to 7; retching replaced overt vomiting in all but two of these seven patients, neither of whom had recurrence of reflux. Because oropharyngeal incoordination was prominent, concomitant use of gastrostomy and an antireflux procedure was especially effective in the treatment of younger patients with familial dysautonomia, before the development of severe respiratory disease. Despite the development of severe morning nausea in 15 patients, the combination procedure resulted in significantly improved nutritional status, decreased vomiting, and decreased respiratory problems. Appropriate use of gastrostomy feedings also contributed to success of the operation. The generally good outcome of fundoplication with gastrostomy confirms the benefit of this procedure in familial dysautonomia.

Adolescent↗
PubMed1989

Establishment of a schedule of optimal preoperative collection of autologous blood.

Autologous blood donation prior to elective surgery can protect patients from unnecessary exposure to allogeneic blood. However, the inappropriate use of autologous blood programs, which results in the collection of excessive quantities of blood or of the collection of any blood prior to low-risk surgical procedures, can be wasteful and potentially hazardous. All patients donating autologous blood at a large institution during a period of three months were studied in an effort to develop a schedule of optimal preoperative collection of autologous blood (SOPCAB), which is similar to a maximum surgical blood order schedule. Some 461 consecutive autologous donations from 264 patients were investigated. For certain surgical procedures, primarily the cardiac and orthopedic procedures, undercollection appeared to be the most common problem. For other procedures (laminectomies, nasal surgery), overcollection was more common. A model is presented for the careful scrutiny of autologous blood collection and use to allow for the creation of a SOPCAB for patients undergoing elective surgery.

Blood Specimen Collection↗
PubMed1987

Optic nerve dysfunction in familial dysautonomia.

We examined 12 patients with familial dysautonomia who had clear corneas to determine if there was any optic nerve involvement. The patients ranged in age from 6 to 34 years. Visual acuity ranged from 20/20 to 20/100. Nineteen eyes of 12 patients (79%) had abnormal (mean +/- 3 S.D.) pattern reversal visual-evoked potentials as compared to 50 control eyes (P100 = 98.8 msec; S.D., +/- 4.5 msec). P100 latency appeared to worsen with age. Exodeviation was present in seven patients (58%) and correlated with visual acuity and P100 latency. Ophthalmoscopic examination showed some degree of optic nerve pallor in all eyes.

Adolescent↗
PubMed1987

Evaluation of autonomic dysfunction in familial dysautonomia by power spectral analysis.

We examined the nature and extent of the autonomic control defect in patients with autonomic dysfunction using power spectral analysis of heart rate fluctuations. Heart rate variability and respiratory patterns were monitored and discrete blood pressure measurements were made during supine and standing positions in 10 ambulatory patients with familial dysautonomia and in controls. Postural hypotension without compensatory tachycardia was confirmed in the patients upon standing. The balance between sympathetic and parasympathetic activity was compared in both positions by quantifying the power of the low (0.04-0.095 Hz) and high (respiratory) frequency fluctuations in instantaneous heart rate. After changing from supine to standing position there was a small decrease in the low frequency power of heart rate fluctuations in the patients as opposed to a significant increase in controls. The mean power of fluctuations occurring at high frequency decreased only slightly in the patients compared to a marked decrease in the controls. We conclude that the fall in blood pressure, lack of appropriate heart rate modulation, and failure to increase low frequency heart rate power which occurred in the patients upon standing, are all due to lack of increased sympathetic output under the influence of gravity. The failure to decrease power in the respiratory frequency peak in the patients, suggests an abnormal retention of parasympathetic activity. This may be explained by parasympathetic compensation for the substantial sympathetic loss, or by a lack of appropriate inhibition of parasympathetic tone from baroreceptors or supraspinal structures.

Adult↗
PubMed1987

Bradycardia associated with hiatal hernia and gastroesophageal reflux relieved by surgery.

A man known to have familial dysautonomia presented with a cardiac arrhythmia due to development of hiatal hernia and gastroesophageal reflux. Preoperative symptoms and assessment are described including use of power spectrum analysis of heart rate fluctuations which was consistent with enhanced parasympathetic stimulation. After surgical repair of hiatal hernia and fundoplication, bradycardia resolved, gastroesophageal reflux symptoms subsided, and the power spectrum analysis of heart rate confirmed decreased parasympathetic influence. Power spectrum analysis proved to be a useful adjunct in confirming preoperative autonomic imbalance and assessing the postoperative result. It is concluded that in individuals with disorders such as familial dysautonomia that are associated with autonomic dysfunction, cardiac arrhythmias may be a sign of esophageal pathology. Thus, cardiac evaluations should be accompanied by investigation of gastroesophageal structure and function and appropriate treatment may prevent a catastrophic arrhythmia.

Adult↗
PubMed1984

Structural gene for beta-nerve growth factor not defective in familial dysautonomia.

The developmental loss of neurons in sympathetic, sensory, and some parasympathetic ganglia in familial dysautonomia suggests an inherited defect in the action of beta-nerve growth factor (beta-NGF). The role of this growth factor in dysautonomia has been difficult to resolve as there is no known source of authentic human beta-NGF. The availability of a cloned DNA probe for the human beta-NGF gene has allowed identification of some copies of the gene (alleles) in six affected families. Alleles differ in the length of restriction endonuclease fragments that hybridize to DNA probes for the gene. In two families, affected children did not inherit the same two alleles at the beta-NGF locus. Since this disease is transmitted in an autosomal recessive manner, affected children must share the same alleles at the locus causing the disease. This analysis excludes the beta-NGF gene region as the cause of this neurologic disease but does not eliminate other genes involved in beta-NGF action, such as those coding for processing enzymes, receptors, or other subunits of the NGF complex.

Alleles↗