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Biomedical subjects

S Appel

Publications and source records attributed to S Appel.

At least 37 records · Page 2Linked to original sources
PubMed1993

High-performance liquid chromatography of the adenosine A1 agonist N6-cyclopentyladenosine and the A1 antagonist 8-cyclopentyltheophylline and its application in a pharmacokinetic study in rats.

This report describes a rapid and sensitive analysis for the simultaneous detection of the adenosine A1 receptor ligands N6-cyclopentyladenosine (CPA) and 8-cyclopentyltheophylline (CPT) in rat blood. The method involved alkaline extraction of the compounds and internal standard N6-cyclohexyladenosine (CHA) with ethyl acetate, followed by isocratic reversed-phase high-performance liquid chromatography on a 3-microns MicroSphere C18 column with UV detection at 269 nm. The mobile phase consisted of a mixture of 10 mM acetate buffer (pH 4.0)-methanol-acetonitrile (56:40:4, v/v/v) with a flow-rate of 0.50 ml/min. The total run time was ca. 19 min. For CPA and CPT extraction yields were greater than 77 and 66% in the concentration range of 0.010-0.75 microgram/ml and 0.025-15 micrograms/ml, respectively, with intra- and inter-assay variations less than 9%. In 100 microliter blood samples the corresponding limits of detection were 3.3 and 6.2 ng/ml (signal-to-noise ratio = 3). CPA was found to be degraded in rat blood in vitro with a half-life of 24 min at 37 degrees C. The utility of the analytical method was established by analyzing blood samples from rats which had received an intravenous administration of 200 micrograms/kg CPA or 12 mg/kg CPT. Due to its rapidity and sensitivity this method is concluded to be particularly useful in pharmacokinetic studies with CPA and CPT.

Adenosine↗
PubMed1993

The two-edged sword of large-dose steroids for spinal cord trauma.

OBJECTIVE: In 1990, large-dose steroid administration was advocated in spine-injured patients to lessen neurologic deficits. The authors undertook both prospective and retrospective studies to evaluate the response of such profound pharmacologic intervention. SUMMARY BACKGROUND DATA: Of all sources of nonfatal injury, spinal cord trauma remains the most devastating in both cost and impact on the quality of the patient's life. One study found that routine large-dose steroid administration after injury lessened the extent of neurologic injury. After uncommonly prompt and broad lay press publicity, this practice was widely accepted. Biased by knowledge of the known immunosuppressive effects of steroids, the authors suspected that pneumonia was both more frequent and severe in steroid-treated patients. METHODS: Thirty-two patients with cervical or upper thoracic spinal injuries (C3-6, 20 patients; C6-7, 6 patients; and T1-6, 6 patients) were studied at an urban level I trauma center from January 1987 to February 1993. Complete spinal cord injury was present in 22 of 32 patients; 14 patients received steroids postinjury. There was no difference in mean age, cord level, age-adjusted injury severity score, or the percent of injury severity score caused by the spinal injury. RESULTS: The length of hospital stay was longer in steroid-treated patients (S) than in nonsteroid (NS) patients, that is, 44.4 days versus 27.7 days, respectively (p = 0.065). Seventy-nine per cent of S patients had pneumonia compared with 50% of NS patients (p = 0.614). There was no statistical difference in the episodes of pneumonia per patient between the two groups (p > 0.05). Prospectively, the authors evaluated sequentially several parameters known to be important in human immune responses to bacterial challenges in nine S and five NS patients. In S patients, both the per cent and density of monocyte class II antigen expression and T-helper/suppressor cell ratios were lower than in NS patients. However, S patients did have an initially higher, earlier boost in some host defense parameters that rapidly declined, and their subsequent response was both blunted and delayed. These differences became even clearer when stratified according to cord level and incomplete versus complete cord status. Not surprisingly, infected patients, whether S or NS, had lower levels of monocyte antigen expression, CR3, and helper/suppressor ratios. CONCLUSIONS: These data do not permit a judgment to be made whether neurologic status was improved by S administration. It is known that vital immune responses were adversely affected, that pneumonia was somewhat more prevalent, and that hospitalization was prolonged and costs therefore increased by an average of $51,504 per admission. Further clinical studies will be needed to determine to what extent these observations offset the putative benefits of large-dose steroids in the treatment of spinal trauma.

Adult↗
PubMed1993

Regional and systemic immune responses in a murine model of empyema.

The extent to which circulating leukocytes reflect functional capacity at the site of infection is unclear despite a century of debate. We conducted experiments designed to clarify those relationships as well as the relationship of pleural and peritoneal responses to infection. Empyema was established in inbred CBA/J mice by introducing Escherichia coli and Bacteroides fragilis into the thoracic cavity through a limited thoracotomy. Walled off abscesses appeared seven days after the introduction of infection. Cell surface expression of murine class II major histocompatibility antigen was measured in peripheral leukocytes, thoracic and peritoneal cavity exudate leukocytes and abscess cells for 60 days after the introduction of infection. The peripheral antibody response was determined by measuring immunoglobulin M (IgM) and immunoglobulin G (IgG) specific for the two organisms. The results demonstrated that, after introduction of infection into the thoracic cavity, mice mounted a specific systemic humoral immune response by producing IgM and IgG. There was a pronounced concomitant cellular response in thoracic and peritoneal cavity exudate cells. However, there was no evidence of a systemic cellular response in circulating lymphocytes or monocytes and polymorphonuclear leukocytes measured as a single group. We conclude from these experiments that measurements of peripheral immune parameters may adequately reveal the humoral response to infection, but it does not reflect the local immune cellular response. Furthermore, a special relationship exists between the peritoneal and the thoracic cavities, whereby an inflammatory process in the thoracic cavity leads to a marked activation of inflammatory process in the peritoneal cavity without affecting peripheral circulating cells to the same extent.

Animals↗
PubMed1992

Regional cellular responses to intraperitoneal infection.

Leucocytes in different body compartments were examined in a murine intra-abdominal abscess model: (i) peripheral blood; (ii) peritoneal exudate; (iii) abscess wall; and (iv) abscess pus, with respect to their phagocytic ability, CR3 expression and Ia antigen expression (murine MHC antigen). The ability of serum or supernatant in each compartment to opsonize Staphylococcus aureus was also determined. Mice responded to caecal ligation and puncture (CLP) with systemic monocytosis, an increased amount of opsonins in peritoneal fluid and an increased phagocytosis in pus leucocytes. This increased phagocytic ability and CR3 expression both subsequently decreased. Monocyte/macrophage Ia expression was reduced in all measured compartments over time. In contrast, sham-operated animals, without an intra-abdominal abscess, responded to operation with an even greater increase in peritoneal exudate phagocytic ability and in monocyte/macrophage Ia expression in all compartments which was sustained beyond 1 week. Decreased peritoneal exudate cell and peripheral blood Ia was still present after 28 days in CLP animals, compared with both sham and normal animals (P less than 0.05, P less than 0.02, respectively). For all parameters, changes observed in peripheral blood did not reflect those present near the site of infection. Proper understanding of local or regional infection must take into account and ultimately alter these generally unappreciated changes in and about the actual site of infection.

Abscess↗
PubMed1992

Evidence for instability of the autonomic nervous system in patients with migraine headache.

Autonomic impairment in migraine is well documented. In order to evaluate the autonomic control in migraine, spectral analysis of heart rate fluctuations was performed on ten migraine patients, drug-free and during the inter-headache phase. They were compared to nine healthy controls and eight tension headache patients. A 24h Holter recording of ECG was performed for each subject. Every half hour, a short ECG subtrace was digitized and submitted to R wave detection, followed by computation of heart rate power spectrum. The spectral analysis of heart rate fluctuations disclosed significant differences between control subjects and patients with migraine. The migraine patients displayed markedly enhanced low frequency fluctuations (below 0.1 sec-1), during day hours (p less than 0.01) and especially at night (p less than 0.0006). In the respiratory frequency band (between 0.2 and 0.4 sec-1) no significant change was observed. Tension headache patients however, resembled the controls in that they did not display enhanced low frequency fluctuations. The enhancement at low frequencies fluctuations only, a frequency range known to be related to vasomotor control, suggests that the migraine patients are characterized by a clear sympathetic instability. This finding supports the hypothesis that migraine is of neural origin and is consistent with the observation of large variations in regional cerebral flow. Spectral analysis of heart rate fluctuations allows us to specify and quantitate this autonomic imbalance and may provide a useful tool for the evaluation of drug therapy in migraine.

Adult↗
PubMed1992

Propranolol in the prophylaxis of migraine--evaluation by spectral analysis of beat-to-beat heart rate fluctuations.

Migraine patients seem to suffer from a continuous autonomic imbalance. Sympathetic instability, expressed by enhanced low frequency fluctuations, which exists during the headache free intervals, was observed in our previous study by spectral analysis of heart rate (HR) fluctuations. Propranolol--a beta adrenoceptor antagonist, is widely used in migraine prophylaxis. In order to specify and quantitate propranolol efficacy in migraine, spectral analysis of heart rate fluctuations was performed on 10 migraine patients before and during the treatment with propranolol. They were compared to 10 healthy control patients and 6 migraine patients who were treated for several months with propranolol and then discontinued the medication. The analysis was carried out on a 24h Holter ECG recording, which was performed for each subject during a headache free interval. Short 256 sec subtraces, taken every 30 min from the 24h ECG signal, were submitted to A/D conversion, R wave detection and computation of heart rate power spectrum. Propranolol achieved a marked effect, when comparing the power spectra of HR fluctuations in treated versus untreated migraine patients. A strong reduction (to normal level) in the low frequency HR fluctuations in the range below 0.1 Hz., was apparent in patients treated with propranolol. Subjects who had received propranolol in the past and discontinued the drug, displayed a carry-over effect of reduced fluctuations even 2-3 months after its discontinuation. It seems that the propranolol efficacy in migraine is associated with the mechanism of stabilizing the fluctuations within the frequency band related to sympathetic activity, hereby moderating the vascular instability in migraine.

Adult↗
PubMed1991

Incidence and prevalence of amyotrophic lateral sclerosis in Harris County, Texas, 1985-1988.

The incidence of amyotrophic lateral sclerosis was determined in Harris County, Texas, for the period 1985 through 1988. Amyotrophic lateral sclerosis cases were ascertained from four sources: area neurologists, hospitals, death certificates, and the Muscular Dystrophy Association. The age-adjusted incidences of 1.27 per 100,000 person-years in males and 1.03 per 100,000 person-years in females were lower than recent rates in the northern US, Canadian, and northern European studies but higher than rates in southern European studies. Comparisons with other recent incidence studies show less uniformity in occurrence of amyotrophic lateral sclerosis, in both the overall rates and in the age- and sex-specific patterns, than was suggested by mortality studies. The incidence of amyotrophic lateral sclerosis among blacks and whites was similar. Hispanic males had incidences similar to white males, although a deficit of female Hispanic cases was found in Harris County. The prevalence of amyotrophic lateral sclerosis peaked in the 65- to 74-year age group at 33 per 100,000 population among males and 19 per 100,000 population for females.

Adolescent↗
PubMed1991

A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis.

We found Cop 1 to be effective and relatively safe in a previous (exacerbating-remitting) clinical trial. This current trial involves 106 chronic-progressive patients. The major end point, confirmed progression of 1.0 or 1.5 units (depending on baseline disability) on the Kurtzke Expanded Disability Status Scale, was observed in nine (17.6%) treated and 14 (25.5%) control patients. The differences between the overall survival curves were not significant. Progression rates at 12 and 24 months were higher for the placebo group (p = 0.088) with 2-year probabilities of progressing of 20.4% for Cop 1 and 29.5% for placebo. We found a significant difference at 24 months between placebo and Cop 1 at one but not the other center. Two-year progression rates for two secondary end points, unconfirmed progression, and progression of 0.5 EDSS units, (p = 0.03) are significant.

Chronic Disease↗
PubMed1988

Determination of lymphocyte subpopulations by enzyme immunoassay. Comparison with conventional fluorescence microscopy.

An enzyme immunoassay for measuring lymphocyte subpopulations was evaluated and the results compared with those obtained with conventional fluorescence microscopy, using two different panels of antibodies. The enzyme immunoassay is a photometric method which expresses the results using a standard curve with known amounts of cells. The method was reproducible and accurate. The intra-assay variation for the standard curve ranged from 3.2 to 5.7% and the interassay variation from 9.5 to 13.8%. The intra-assay variation for clinical samples ranged from 3.3 to 8.2%. Results obtained with the enzyme immunoassay and with conventional fluorescence microscopy showed a significant correlation (P less than 0.05) for all the subclasses of lymphocytes tested using two different panels of monoclonal antibodies. We conclude that the choice of method should be related to the particular needs and manpower in the laboratory.

Adult↗
PubMed1987

Distributions of total cholesterol, triglycerides, and high-density lipoprotein cholesterol in Israeli Jewish children of different geographic-ethnic origins, ages 9-17 years.

To determine age and ethnic patterns of blood lipid levels in childhood and adolescence and to extend previous adult and late adolescent Israeli data to prepubertal ages, the levels of plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined among 1,153 schoolchildren in the area of Petah-Tikva. Half of the children were born to immigrants from Yemen. Among boys, TC levels progressively decreased as age increased from 10-11 to 14-15 years (159 to 142 mg/dl). The age-specific TC and HDL-C means among boys are compatible with an initial swift fall with age, followed by a rise restricted to TC during puberty. Among girls, progressively lower means through ages 12-13 and increasingly higher ones for older age groups are also compatible with puberty-determined changes, previously observed in American cohorts. The differences in TC were only partly accounted for by lower HDL-C means at higher ages (52 mg/dl in the youngest and 45 mg/dl in the oldest age group, respectively, among boys, compared with 53 mg/dl for girls at both ages 9 and 16-17). TG levels in boys, but not in girls, showed age differences paralleling those found for HDL-C, but in an inverse direction. TC means were lower as age increased only among female offspring of European-born Jews (159 to 148 mg/dl, ages 9-12 compared with ages 13-17), a phenomenon that requires further study. Overall, TC and HDL-C were clearly higher among girls than boys beginning at ages 12-13, with little or no sex differences in TG. The sex differences in TC, contrary to previous studies, were not fully accounted for by HDL-C sex differences. The ethnic variability paralleled previous findings in Israeli adults and adolescents, showing low TC levels among male offspring of Yemenite and other Asian-born fathers. The ethnic differences among girls were small. No specific pattern of age-related lipid changes was found in the group of Yemenite origin, who represented offspring of parents with notoriously low levels of coronary heart disease incidence.

Adolescent↗
PubMed1982

Retrolental fibroplasia: a medical dilemma.

Retrolental fibroplasia (RLF) remains as a leading cause of visual impairment in infants. The pathophysiology of RLF is discussed as well as the significant risk factors. The clinical course of the disease is considered including the various stages of RLF and the differential diagnosis. Finally, the management and treatment options of RLF are discussed.

Diagnosis, Differential↗
PubMed1981

Cultured muscle from myotonic muscular dystrophy patients: altered membrane electrical properties.

Myotonic muscular dystrophy (MyD) is an inherited human disease involving skeletal muscle as well as many other organ systems. We have approached the study of this disorder by growing normal and diseased human muscle in a primary tissue culture system and investigating some of the electrical properties of the resulting myotubes. The most distinctive abnormality noted in MyD myotubes was an increased tendency to fire repetitive action potentials. A decreased action potential afterhyperpolarization amplitude and the presence of depolarizing afterpotentials were also noted, as were a decreased resting membrane potential, decreased action potential amplitude and overshoot, and decreased outward-going rectification. Although the ionic basis of these abnormal properties in vitro is not clearly defined, changes in the slow outward-going potassium current offer the best explanation. Furthermore, MyD cell culture offers a valuable model for critical analysis of the molecular mechanisms underlying MyD deficits.

Action Potentials↗