Tyramine kinetics and metabolism in cirrhosis.

Hypertyraminemia is common in hepatic cirrhosis and correlates in severity with encephalopathy. The mechanism of cirrhotic hypertyraminemia has not been established. The alternative possibilities are increased production from tyrosine and impaired degradation by monoamine oxidase. This investigation determined the pharmacokinetics of tyramine after an intravenous bolus injections of [3H]-tyramine (180--200 muCi 12 Ci/mmol sp act) in 13 cirrhotics and 9 controls. In normals, [3H]tyramine levels initially declined rapidly (alpha-phase) followed by a slower decline (beta-phase) with an average t 1/2 of 20.8 min. Average normal metabolic clearance rate and production rate were 13.2 liters/min and 15.4 microgram/min, respectively. In cirrhotic patients, the plasma disappearance curve for [3H]tyramine was qualitatively similar to that of the control subjects with no apparent different in beta-t 1/2 (17.2 min). The hypertyraminemia of cirrhosis resulted primarily from overproduction of tyramine, as the production rate (32.0 microgram/min) in these patients was significantly greater (P less than 0.05) than in controls, whereas the metabolic clearance rate remained normal (average 12.2 liters/min). A difference in ratio of tyramine metabolic products was noted as well. Cirrhotics had a high ratio of plasma 4-hydroxyphenylethanol:4-hydroxyphenylacetic acid (60:40 vs. 30:70) as compared with normals. Although the tyramine clearance rates are similar in normals and cirrhotics, different mechanisms may be responsible for catabolism.

What do primary care patients think about generic drugs?

OBJECTIVE: To examine the attitude of patients towards generic drugs and prescriptions containing generic drugs as an alternative to brand-name products, with a special focus on information on patients attitude to generic drugs provided by their general practitioners (GPs). METHODS: A total of 804 patients in 31 general practices were surveyed using a self-questionnaire. The influence of age, sex, education, disease, knowledge of generic drugs, experience with generic substitution and information provided by the GP on patient attitudes towards generic drugs and substitutions were examined. RESULTS: Nearly two thirds of the patients (509/804) stated that they knew of the difference between brand-name drugs and generics; of these, one third were not satisfied with the information given by their GPs and 37% of patients expressed general skepticism towards generic drugs because of their lower price. This attitude was more frequent among those who felt that generic prescribing was "invented" to solve the financial crisis in the German health insurance system at their expense (odds ratio (OR): 6.2; 95% confidence interval: 4.0 - 9.8) and those who had not been confronted personally with a generic substitution (OR: 1.8; 1.3 3.0). Patients who had been skeptical when first confronted with a generic substitution were more frequently among those who considered inexpensive drugs to be inferior (OR: 4.5; 2.0 10.4) and they were frequently not satisfied with the information on substitution provided by their GP (OR: 2.7; 1.2 - 5.9). CONCLUSION: GPs are in an ideal position to inform their patients adequately about the equivalence of brand-name and generic drugs. However, the patient view that inexpensive drugs must be inferior may be difficult to rectify in the short term.

Nasogastric hyperalimentation through a polyethylene catheter: an alternative to central venous hyperalimentation.

We performed nasogastric hyperalimentation with polyethylene catheters and appropriate feeding solutions in 12 cachectic patients who had been referred as candidates for central venous hyperalimentation. Most patients had primary gastrointestinal disease. The duration of hyperalimentation averaged 31 days. Seven patients obtained rapid weight gain (average 0.3 kg/day) with the nasogastric hyperalimentation alone. An additional two were successfully repleted with the addition of parenteral fluids via peripheral veins. In the nine repleted patients, serum albumin rose by average 19%, 24-hr urine creatinine by average 21%, and triceps skinfold by average 46%. The nature of the weight gain in the nine successful cases was analyzed by the metabolic balance study technique. Average composition of the increment in weight was: 50% protoplasm, 48% extracellular fluid, 19% adipose tissue, and less than 1% bone. We conclude that nasogastric hyperalimentation can replace central venous hyperalimentation in a substantial proportion of patients now receiving the latter type of treatment.

Iatrogenic respiratory distress syndrome following elective repeat cesarean delivery.

OBJECTIVE: To determine the incidence of iatrogenic respiratory distress syndrome (RDS) following elective repeat cesarean delivery and to identify whether it was associated with departures from accepted management guidelines. METHODS: Between January 1986 and March 1991, there were 23,125 deliveries at Northwestern Memorial Hospital, of which 1207 were repeat cesarean births without labor. During this period, 18 neonates of 37 weeks' gestation or greater or 2500 g or greater who were delivered by elective repeat cesarean were admitted to the neonatal intensive care unit (NICU) for respiratory difficulties. RESULTS: Five of the 18 neonates admitted to the NICU with respiratory difficulty following elective repeat cesarean delivery met the criteria for RDS. This represents an incidence of 0.41% (five of 1207), or one case of RDS for every 241 repeat cesarean deliveries without labor. Four of the five neonates required mechanical ventilation for an average of 6.8 days. The average NICU stay was 11.2 days. Complications included pneumothorax (one) and pulmonary hemorrhage (one). Departures from accepted management guidelines included a discrepancy between ultrasound and menstrual dates (two), no confirmation of menstrual dates (one), and delivery before 39 weeks' gestation (two). CONCLUSION: Iatrogenic RDS continues to occur in the setting of elective repeat cesarean delivery and is associated with a failure to adhere to clinical protocols.

The energy content of infant formulas.

The reported energy content of infant formulas will vary, depending upon the method used to calculate or measure the caloric value. Manufacturers' specifications regarding the energy content of milk formulas reflects the 'metabolizable' energy. i.e., the amount of energy which is digested and absorbed by the infant. However, estimates of absorptive efficiency are based primarily upon studies in young adult subjects fed mixed diets and therefore may not be generally applicable to all neonates. The actual caloric content of formulas may be determined accurately by bomb calorimetry which is not influenced by the relative metabolic efficiency of the infant who may utilize the formula. Therefore, it may be preferable to express the caloric value of milk base formulas in terms of absolute combustible energy.

Cardiopulmonary resuscitation of the newborn. An update.

The abrupt transition from intrauterine to extrauterine life represents a series of profound physiologic changes. This process puts the baby at risk for asphyxia. At birth, the newborn is, therefore, more frequently in need of resuscitation than at any other age. This article reviews the rationale for the sequence and process of neonatal resuscitation, emphasizing recent changes in recommendations.

Use of complementary healthcare practices among chiropractors in the United States: a survey.

CONTEXT: Although chiropractic is the most commonly used complementary healthcare practice, chiropractors have not been surveyed in depth about their attitudes toward and practice of complementary and alternative therapies apart from spinal manipulation. OBJECTIVES: To examine attitudes among US chiropractors on the role of their profession in complementary healthcare and to gather data on the types of complementary healthcare practices chiropractors use. DESIGN: Descriptive, cross-sectional study using a mail-in survey. SETTING: United States. PARTICIPANTS: Random sample of US chiropractors stratified by zip code region. RESULTS: A total of 563 surveys were completed, for a response rate of 30%. Respondents were almost equally divided on their responses to the question "Do you feel that chiropractic should at the present time be termed 'complementary'?" Although many respondents (68%) believed that chiropractic was viewed as a therapeutic modality, more (82%) believed that it should be viewed as a complete system. The therapies most commonly used by respondents in their practice were acupressure (72%), massage (72%), mineral supplements (63%), and herbs (56%). CONCLUSION: The disparity between the established view of chiropractic as synonymous with spinal manipulation and the profession's view of chiropractic as a complete system indicates a need for better interprofessional communication.

Diagnostic illusions: the reliability of random chance.

A "Monte Carlo" experiment was performed in order to determine chance concordance rates for multiple test scenarios often encountered in chiropractic diagnosis. The Monte Carlo simulation took into account the following variables: the number of tests involved in the diagnosis; the number of vertebral segments implicated by each test; the proportion of tests in agreement relative to the number of tests performed; and the segmental margin of error accepted. Random data for up to five diagnostic tests performed on 500 "patients" were computer generated and a wide variety of test scenarios analyzed. One typical analysis asked: if four diagnostic tests are performed on each patient, each test implicating on average three vertebral segments, and a plus or minus one segment error margin is accepted, what are the chance odds that any three out of the four tests will implicate the same vertebral segment? The answer, determined by simply counting how often this happened in the 500 "patients," was 89%. Many test scenarios yielded chance levels much higher than might have been expected. High probability situations as well as those test criteria yielding relatively low chance concordance rates are identified.

An estimate of the effect of acute exsanguination on catecholamine and glucoregulatory hormone concentrations in the newborn rat.

We have determined the effect of acute exsanguination on plasma concentrations of glucose, insulin, glucagon, dopamine, epinephrine and norepinephrine in neonatal Sprague-Dawley rats. This was done by comparing concentrations of these substances in aliquots of blood obtained within 10 s of the initial bleeding to those in blood obtained over the next 50 s of the blood drawing process. Concentrations of glucose and insulin showed no change between early and late samples. Glucagon concentrations showed variable responses dependent upon the age of the animal. Concentrations were unchanged at birth, but increased 22% and 58% at 1 and 6 h of age respectively. Catecholamine concentrations increased greatly (57 to 215%) between blood aliquots regardless of age at the time of sampling. These findings indicate that hormonal responses occur during the relatively brief period of blood drawing in Sprague-Dawley rats, pointing out further limitations inherent in the use of small animals for acute metabolic and hormonal studies.

Concordance between galvanic skin response and spinal palpation findings in pain-free males.

The concordance between areas of paraspinal low resistance, i.e., galvanic skin response (GSR) and positive palpatory findings in pain-free male subjects was investigated. The concordance between vertebral segments implicated by GSR and by palpation was not found to be significantly different from chance concordance as determined by a t-test comparison of experimental results to randomly generated simulations, and by the application of Cohen's Kappa index of concordance to experimental data. This was true even when the locations of low resistance areas along the dorsal trunk were compared to only those vertebral palpatory findings rated as "severe." When test-retest reliability of GSR was examined, only 27% of vertebral segments implicated by GSR on initial examination were also implicated in the same subjects 4 h later. It was noted that low resistance areas detected by GSR were always punctate in nature and appeared to correspond well to known acupuncture loci. Further investigation revealed that, indeed, the GSR unit was not only effective in locating those acupuncture points that happened to be in a state of lowered resistance at the time but was also able, within about 5 sec, to decrease the resistance of any particular point not already in its lowest state of resistance to a level sufficient to generate a positive and persistent GSR reading where none had been detected previously. It is suggested that GSR may not be a reliable predictor of the location of vertebral pathology, at least as assessed by palpation in pain-free subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of soft tissue strain in response to consecutively increased compressive and distractive loads on a friction-based test bed.

PURPOSE: To abstract the essential elements of chiropractic prone leg checking and subject them to controlled, experimental parametric testing. DESIGN: Controlled, objective, repeated-measure analysis of the dynamic response of leg positions to distractive and compressive loading conditions. SETTING: Research laboratory in a chiropractic college. PARTICIPANTS: Twenty-five compression and 30 distraction subjects, most of whom were male, asymptomatic chiropractic students. INTERVENTION: The subjects were lowered to the prone position on a table optimized to detect dynamic leg positions, with separate sliding segments supporting each leg. A trial consisted of a 2-min control run, followed by two 2-min experimental runs in which compressive or distractive loads were applied incrementally to the table-leg segments. MAIN OUTCOME MEASURE: An optoelectric system measured real-time absolute and relative leg positions. RESULTS: Right legs showed a greater average response than left legs under both distractive and compressive loads, and tended to respond more proportionately to incremental load increases. The average response to compression exceeded the response to distraction. Both legs showed a greater average response in the second half of the trials. Correlation of weights with responses was about four times greater in traction than compression. CONCLUSION: The functional short leg is confirmed as a stable clinical reality, a multitrial mean of unloaded leg positional differences. The prone leg check may be a loading procedure, albeit unmeasured, that detects non-weight-bearing, functional asymmetry in loading responses. These probably reflect differences in left-right muscle tone, joint flexibility and tissue stiffness. The relatively nonmonotonic, nonlinear quality of left leg responses is consistent with asymmetric neurological responses.

Effects of asphyxia at birth on postnatal glucose regulation in the rat.

We have characterized the effect of a period of asphyxia at birth, followed by recovery, upon newborn rats. Asphyxiated pups were subjected to 3 to 5% (v/v) inspired oxygen during the first 20 min of life and then maintained in room air for 6 h. Control pups were maintained in room air throughout the 6-h period. Hypoxia produced severe asphyxia as reflected by a pH of 6.76 +/- 0.05, PaCO2 of 87 +/- 3 mm Hg and PaO2 of 15.4 +/- 4 mm Hg, and by a greatly increased blood lactate/pyruvate ratio. Plasma catecholamine concentrations in asphyxiated pups were elevated (epinephrine 13,866 +/- 250 pg/ml, norepinephrine 9611 +/- 1813 pg/ml) compared to control animals (epinephrine 973 +/- 234 pg/ml, norepinephrine 774 +/- 133 pg/ml) at 20 min. Asphyxia initially increased plasma glucose concentration, and then with recovery it fell below controls. Hepatic glycogen stores did not differ between asphyxiated and control pups. Plasma insulin concentrations remained elevated during asphyxia and the usual neonatal surge of plasma glucagon was significantly delayed. Neonatal asphyxia increases catecholamines, causes lactic acidemia, and alters insulin and glucagon levels. The interactions between these variables alters the normal pattern of glucose availability during the neonatal period.

Attentional alterations of slant-specific interference between line segments in eccentric vision.

Slant-specific interference between line segments in eccentric vision was altered by attentional methods in hypnotically susceptible observers. These methods included negative and positive posthypnotic hallucination of the inducing elements of the array, and nonhypnotic instruction to actively ignore the elements. Contributions to the experimental effects apparently derived in part from intrinsic inhibitory or facilitatory skill in the individual observer, sharpened by hypnotic training in hallucinations. Control observers with low and with high hypnotic susceptibility were not able to alter significantly the interference effect when attempting to simulate the hallucination conditions. The results seemingly link these attentional alterations to an early cortical stage of visual processing.

Power spectral and microvector frequency analysis of dynamic standing foot force patterns in a normal male subject.

Power spectral and microvector frequency analyses of dynamic standing foot force patterns in a normal male subject were performed using a multiple-trial experimental protocol. Power spectral analysis of eight eyes-open vs. eyes-closed 50-sec trials revealed significant power increases in the 0.14 to 0.66 Hz range with eye closure, which were repeatable in trials performed on the same subject 2 wk later. Since power spectral differences are difficult to interpret biomechanically, a (micro)vector analysis of 1/20 sec changes in proportional weight transfer was employed. This methodology was able to reveal that foot force weight transfer exhibited a distinct preferred directionality, and that the eyes-closed condition was characterized by significant increases in both the occurrence and average magnitudes of these preferred microvectors.

Analysis of dynamic standing foot force patterns in a normal male subject by characterization of microvector weight transfer sequences.

Previous foot forceplate analyses in our laboratory have shown that postural sway in a normal male subject induces net weight transfers (microvectors) which have preferred directionalities, and that eye closure is characterized by increases in both the occurrence and magnitudes of these preferred microvectors. The same data generated from 8 x 8 blocks of eyes-open and eyes-closed trials were reanalyzed to examine microvector temporal sequences (i.e., macrovectors). Macrovectors were defined by the number of successive microvectors occurring along the same general direction, (anterior, posterior, right or left). Results suggest that with eye-closure, proprioceptive systems are unable to maintain lateral sway deviations within eyes-open limits. This instability increases lateral macrovector durations while only marginally affecting sagittal macrovector durations.

Normal paraspinal tissue compliance: the reliability of a new clinical and experimental instrument.

Test-retest reliability of a hand-held tissue compliance meter was evaluated in 20 normal subjects at four paraspinal locations to determine possible effects of probe response or other sources of variability on measurements taken 10 min later at exactly the same location. If tissue compliance, as measured by this instrument, is to be used in a pre-post context to evaluate treatment effects, caution is urged, since 26% of the sites were significantly (+/- 1.96 SD) different on 10 min retest though subjects remained supine and without intervention. In addition, since 85% of these normal subjects displayed at least one paraspinal compliance asymmetry large enough to qualify as pathological by Fischer's criteria, revision of these criteria may be appropriate, at least for these paraspinal locations.