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PubMed1993

Comparison of toxicities of acrylamide and 2,5-hexanedione in hens and rats on 3-week dosing regimens.

Survival rates, changes in body weight, gait/ataxia scores, and neuropathological lesions were compared between adult Long-Evans rats and adult White Leghorn hens given equivalent dosages of the peripheral neurotoxicants acrylamide and 2,5-hexanedione (12, 25, and 50 mg/kg acrylamide 3 times per week; or 75, 105, 150, 225, or 350 mg 2,5-hexanedione/kg/d, with hens receiving the lowest 3 dosages of 2,5-hexanedione and rats receiving the highest 3 dosages of this test compound). All rats survived the 3-wk acrylamide study period, although those given 50 mg/kg did not gain weight and showed alterations in gait. Hens given 50 mg/kg acrylamide were moribund by 2 wk and were sacrificed before the end of the 3-wk study period. By this time they had lost 29 +/- 3% of their body weight, but none showed significant renal or hepatic lesions on necropsy. Hens given all doses of acrylamide showed dose-related ataxia, weakness, and depression. Gait changes were seen in rats given the high dose of acrylamide for the 3-wk test period. Neuropathological studies revealed that both rats and hens given acrylamide had distal myelinated fibers with dose-related neurofilament-rich axonal swelling and Wallerian-like degeneration, better developed in the rodents. In addition, high-dose acrylamide rats had recent necrosis of cerebellar Purkinje cells. Deaths occurred in all groups of hens given 2,5-hexanedione (75, 105, or 150 mg/kg) before sacrifice at 3 wk, but all rats given 2,5-hexanedione (150, 225, 350 mg/kg) survived a 4-wk study period, even though gait changes were evident in the 225 and 350 mg/kg dosage groups by 3 wk. Neither hens nor rats dosed with 2,5-hexanedione for 3 wk had significant neuropathic lesions, although the hens showed dose-related ataxia, weakness, and depression. Early neurofilamentous intraaxonal masses in distal levels of selected myelinated tracts were seen in rats given the high dose of 2,5-hexanedione for an additional week. These studies suggest that hens are sensitive to acrylamide and 2,5-hexanedione toxicities, and that the rat is more likely than the hen to develop neuropathological lesions.

Acrylamide↗

PubMed1988

Impaired vagal heart rate control in aortic valve stenosis.

Impaired reflex control of heart rate seems to be associated with increased risk of sudden cardiac death. To assess the effect of aortic valve stenosis on parasympathetic heart rate control we measured the heart rate responses to deep breathing and to standing up, non-invasive measures of cardiac parasympathetic activity, in 24 patients with valvular aortic stenosis and in 24 healthy asymptomatic subjects of the same age group. All but one of the patients were symptomatic and the mean aortic valve pressure gradients ranged from 32 to 114 mmHg. The heart rate response to deep breathing was significantly (P less than 0.05) lower in valve patients than in the healthy subjects. The heart rate changes evoked by standing up, however, did not differ significantly between the groups. The heart rate response to deep breathing was inversely weakly related to the left ventricular end-diastolic pressure (r = -0.41, P less than 0.05), but not significantly to the aortic valve pressure gradient, valve area, left ventricular ejection fraction or presence of coronary artery disease. Our results suggest that the impairment of reflex heart rate control is common in patients with significant aortic valve stenosis.

Adult↗

PubMedDate not supplied

Protective action of cimetidine against ouabain-induced pressor effects, arrhythmias, and lethality in guinea pigs.

The effect of the H2-receptor antagonist cimetidine on ouabain cardiotoxicity was studied in anesthetized guinea pigs. Ouabain, infused intravenously at 3.0 micrograms X kg-1 X min-1, was lethal in a dose of 44.0 +/- 3.5 micrograms (n = 6). All control animals died in ventricular fibrillation. Cimetidine, infused concurrently at 10, 30, and 100 micrograms X kg-1 X min-1, significantly increased the lethal dose of ouabain and delayed the onset of various arrhythmias and fibrillation. Cimetidine abolished ouabain-induced pressor effects that have been reported to be neurally mediated; the course of heart-rate changes in ouabain-treated animals, however, was unaffected by cimetidine. In vitro, cimetidine had no effect on the inotropic action of ouabain at concentrations as high as 10(-4) M, whereas serum levels of cimetidine in protected animals did not exceed this concentration. When the ouabain infusion rate was reduced by 50% (to 1.5 microgram X kg-1 X min-1), the lethal dose increased to 72.7 +/- 4.7 micrograms (n = 6), the predominant mode of death changed from fibrillation to cardiac standstill, ouabain-induced pressor effects were absent, and cimetidine no longer exhibited a protective action. Taken together, these findings support the hypothesis that cimetidine acts primarily against indirect components of digitalis toxicity, and so may be potentially valuable for increasing the margin of safety of the cardiac glycosides.

Animals↗

PubMed1999

Impaired vagal reflex activity in insulin-resistant rats.

Insulin resistance, without frank diabetes, is associated with sudden cardiac death. We postulated that a potential mechanism for this association is autonomic dysfunction. Male Sprague-Dawley rats were randomized into one of two groups: (a) insulin resistant (IR; n = 15), or (b) control (n = 11). Animals were made insulin resistant with a fructose-rich diet, whereas control animals received standard rat chow. Four weeks after randomization, arterial pressure and baroreceptor reflex were assessed. Baroreflex sensitivity was defined as the heart-rate response to acute blood pressure changes caused by nitroprusside (0.5-18 micrograms) or phenylephrine (0.2-3 micrograms). To determine the role of vagal stimulation specifically, each animal was randomized to receive atropine sulfate (1 mg/kg) or vehicle (normal saline) before administration of phenylephrine. Mean arterial pressure and fasting insulin concentrations were increased in the insulin-resistant group, whereas there were no differences in body weight, fasting glucose concentrations, or resting heart rate. Phenylephrine increased arterial blood pressure to a maximum of 54 +/- 2 mm Hg for control and 45 +/- 6 mm Hg for IR, p = 0.7. The maximal heart-rate change response to the increased blood pressure was markedly blunted in IR as compared with control (-88 +/- 12 beats/min for IR vs. -238 +/- 18 beats/min for control; p < 0.001). Thus the baroreflex sensitivity (BRS) was threefold less in IR versus the control group (-1.8 +/- 0.2 vs. -4.6 +/- 0.7 beats/min/mm Hg; p = 0.001). Pretreatment with atropine sulfate decreased the BRS in both groups, eliminating the difference between groups (-0.96 +/- 0.5 beats/min/mm Hg for control and -0.56 +/- 0.3 beats/min/mm Hg for IR; p = 0.2). Thus atropine sulfate caused the phenylephrine-induced heart rate and arterial blood pressure response to be equal between groups. On the other hand, BRS to nitroprusside-induced blood pressure changes were similar between groups. Insulin resistance, without the confounding factors of obesity, diabetes, and significant hypertension, is associated with a large reduction in vagal activity, which occurs via attenuation in reflex activity. In contrast, the insulin-resistant syndrome does not affect baroreflex sensitivity via sympathetic reflex.

Animals↗

PubMed1997

Latitude, coastal or interior location and the evolution of the melanoma epidemic in the United States.

Estimates derived from linear models fitted to melanoma death rates at successive time periods for the contiguous states of the US suggest that, allowing for latitude, rates are higher in the coastal than in the interior states. The effect of latitude on melanoma death rates in the white population of the US is decreasing and will shortly be gone. This decrease is slower in the interior states than in the coastal ones. The deceleration of the rate change is most marked in the states with the highest rates, so that latitude may be regarded as a determinant of the initial rate for each state, while the subsequent change in rate is a function of that initial rate. Melanoma death rates appear to be stabilizing at levels that are unaffected by latitude.

Disease Outbreaks↗

PubMed1984

Fetal responses to vibrotactile stimulation, a possible predictor of fetal and neonatal outcome.

This study measured the antenatal fetal heart rate changes in response to a single vibrotactile stimulus. In a group of 11 normal patients, this resulted in a significant change in the fetal heart rate (P less than 0.001). Sixty-eight high risk patients were also tested. In the group of 25 patients whose fetuses showed no response to the stimulus, there were 4 stillbirths and 4 neonatal deaths; 23 of these 25 infants were small for gestational age (SGA) compared to only 15 of the 43 that showed a response to the stimulus. Fetal habituation to a repeated vibrotactile stimulus was measured in a control group of 40 patients who had a normal antepartum and intrapartum course and delivered infants in an optimal condition. The same was done in a study group of 48 patients who delivered infants that were SGA. These infants were assessed at 1 year of age by the Griffiths Mental Developmental Scale (GMDS). Infants that were SGA did not differ significantly from the control group. However, infants who had a normal antenatal habituation pattern had a significantly better performance (P less than 0.01) compared to infants who had an abnormal antenatal habituation pattern.

Electrocardiography↗

PubMed1985

Changes in obstetric practice in our time.

In the years since 1939 there has been a marked change in the nature and results of obstetric practice at the Royal Women's Hospital, Melbourne. The noteworthy changes have been a reduction in the number of maternal deaths (from 12.2 per 1,000 in the 1940's to 0.2 per 1,000 in the 1980's), especially those due to septic abortion, and an increase in the Caesarean section rate (from 2% to 14%). The increase in the operative delivery rate has been matched by a decrease in mortality in patients thus delivered, the maternal and perinatal mortality rates changing from 5.5 and 88.9 per 1,000 to 0 and 7.6 per 1,000 respectively in the case of forceps delivery and from 24.7 and 162.5 per 1,000 to 0.15 and 10.6 per 1,000 respectively in the case of Caesarean delivery.

Adult↗

PubMed1996

Causes of increasing mortality in a nursing home population.

OBJECTIVE: To examine the roles played by changes in case-mix, quality of care, and aggressiveness of care in explaining the 42% increase in mortality of the Medicaid nursing home population of Hennepin County, Minnesota, between 1984 and 1988. DESIGN: Retrospective chart review. SETTING: All nursing homes in Hennepin County, MN, that care for Medicaid patients. PATIENTS: A random sample of 1605 Medicaid nursing home residents from 1984 and 1988 stratified by year and by whether the resident died in that year. Sampling was disproportionate to allow approximately 400 individuals per stratum. A total of 1405 charts (87%) were reviewed; the remainder were either lost or destroyed. MAIN OUTCOME MEASURES: Measures included case-mix (Charlson index, functional status, implicit reviewer assigned severity [range 1-4]), aggressiveness of care (orders limiting care), quality of care (process of care for tracer conditions [range 1-5], falls), and resident death. RESULTS: Implicitly rated severity of illness worsened between 1984 and 1988 (2.77 vs 2.91; P = .009), but other measures of case-mix were unchanged. A greater percentage of residents had a DNR order in 1988 (12% in 1984 vs 37% in 1988; P < .001), and more received less aggressive care (31% vs 40%; P = .006). Overall process of care improved between 1984 and 1988 (2.88 vs 3.01; P < .05). With adjustment of the mortality rates and with logistic regression controlling for age and gender, changes in quality of care alone accounted for less than 5% of the mortality rate change between 1984 and 1988, case-mix alone accounted for 49%, and aggressiveness of care alone accounted for nearly 100%. CONCLUSIONS: The nursing home population became sicker between 1984 and 1988, but process of care improved. These changes had a modest effect on the mortality rate. The increase in less aggressive care between 1984 and 1988 accounts for nearly all of the increase in mortality.

Aged↗

PubMedDate not supplied

Autonomic reflexes in preterm infants.

Some autonomic nervous reflexes often tested in adult medicine have been studied in 21 preterm infants (25-37 gestational weeks). The aim was to develop such tests for preterm infants and see if there were any differences in babies with recurrent apnea and bradycardia and babies who had been exposed to sympathicolytic drugs before birth. To test sympathetic nervous activity the peripheral vascular resistance was measured before and during 45 degrees of head-up tilting. To test parasympathetic nervous activity the degree of bradycardia was measured in response to cold face test (application of an ice-cube on the fore-head) and laryngeal stimulation with saline. Finally the heart rate changes after a sudden noise (85 dB) were studied as an indicator of both sympathetic and vagal activity. The peripheral resistance was found to be relatively low in these preterm infants, particularly in some infants tested at the postnatal age of about two months. Heart rate and mean blood pressure did not change during tilting, while the peripheral resistance increased significantly mainly due to lowered limb blood flow. The median decrease of the heart rate during the cold face test was 20.0% and during laryngeal receptor stimulation 23.7%. The sudden noise usually caused a biphasic heart rate response. An autonomic nervous reflex score was calculated and found to be negative (parasympathetic) in infants with recurrent prolonged apnea and bradycardia and positive in infants with clinical signs of increased sympathetic nervous activity.

Apnea↗

PubMed1982

Relationship between fluorescein diacetate-stained hyphae and oxygen utilization, glucose utilization, and biomass of submerged fungal batch cultures.

The relationship between fungal activity and staining with fluorescein diacetate (FDA) was investigated by growing Penicillium citrinum and Rhizoctonia solani in submerged batch cultures at different initial glucose concentrations and aeration rates. A modified FDA staining method, similar to the Jones and Mollison technique (P. Jones and J. Mollison, J. Gen. Microbiol. 2:54-69, 1948), was developed to assess both total and FDA-stained hyphae. In previous studies, soil hyphae stained with FDA were considered viable. However, determination of a quantitative relationship between FDA staining and fungal activity is necessary before such an assumption can be made. Growth rates and the rate of change in the percentage of FDA-stained hyphae were significantly correlated. The regression equation calculated for the relationship was: growth rate (mg . ml-1 . h-1) = 0.34 + 1.1 (rate of change in the percentage of FDA-stained hyphae [. ml-1 . h-1]). Changes in activity as measured by O2 utilization, glucose utilization, and biomass correlated significantly with changes in the percentage of FDA-stained hyphae, although the relationships among these parameters were different for each fungal species. Fungal growth stage was also correlated with the percentage of FDA-stained hyphae. Staining was 10% or greater during fungal growth and less than 10% during the late growth, stationary, and death phases. Thus, the rate of change in the percentage of FDA-stained hyphae can be used to predict fungal activity rate changes for single fungal cultures and growth rates for mixed fungal cultures, and the growth stage can be assessed by the percentage of FDA-stained hyphae.

Aerobiosis↗

PubMed1996

Reduced heart rate variability after right-sided stroke.

BACKGROUND AND PURPOSE: Recently, asymmetries have been demonstrated in skin sudomotor and vasomotor function after unilateral cerebral lesions. The present study was performed to determine whether other bedside tests reflecting sympathetic and parasympathetic cardiovascular functions would reveal differences with respect to the side of cerebrovascular lesions. METHODS: Heart rate variability during deep breathing as well as blood pressure and heart rate changes during tilt and isometric handgrip was measured in a group of patients with a monofocal stroke and compared with similar data from age-matched patients with transient ischemic attack and healthy control subjects. RESULTS: Compared with left-sided stroke and with the control subjects, stroke location on the right side was associated with a reduced respiratory heart rate variability (P > .01), a reflex mainly under parasympathetic control. In contrast, reflexes mainly reflecting peripheral sympathetic function were equal for right- and left-sided lesions. CONCLUSIONS: Since an imbalance in cardiac autonomic innervation may be crucial for the generation of cardiac arrhythmias and since reduced heart rate variability has been associated with increased mortality, the findings suggest that the risk of sudden death may be correlated with lateralization and location of the brain infarct after stroke.

Analysis of Variance↗

PubMed1992

Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome.

Infants who subsequently succumb to the sudden infant death syndrome (SIDS) have higher heart rates and reduced heart rate variation compared with other infants. We examined dynamic changes in cardiac interbeat intervals to explore these differences in cardiac control. Recordings of electrocardiographic activity and respiratory movement were acquired from 13 SIDS victims before their deaths. Moment-to-moment changes in R-R intervals during quiet sleep, rapid eye movement sleep, and waking were compared with values of 13 matched control infants. For each sleep-waking state, every R-R interval was plotted against the previous interval (Poincaré plots), and each change in interbeat interval was plotted against the previous change. Dispersion of interbeat intervals at different heart rates was reduced in SIDS victims, resulting in Poincaré plots markedly different from those of controls. The dispersion, sampled at the 10th and 90th percentiles of heart rates, was reduced across all sleep-waking states in SIDS victims. At high heart rates, the difference between groups disappeared after correcting for basal rate; however, the reduced range at low heart rates was independent of basal rate. SIDS victims also showed smaller beat-to-beat changes in heart rate and fewer sustained runs of consistent heart rate changes during waking relative to controls. The differences in cardiac rate dynamics suggest altered autonomic control in infants who succumb to SIDS. We speculate that the autonomic disturbance may lead to cardiac instability or may indicate CNS alterations with the potential to affect other vital functions.

Autonomic Nervous System↗

PubMed1991

Circadian variation of myocardial ischemia in patients with stable coronary artery disease.

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression greater than or equal to 1 mm and duration greater than or equal to 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low--28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.

Adult↗

PubMed1997

Fertility levels and trends in the face of the AIDS epidemic in Uganda.

The paper uses data on ever-married women interviewed in 1992 and 1995 surveys in six districts of Uganda. Total fertility rates declined during the inter-survey period from 7.3 to 6.0. Women in households that experienced AIDS-related deaths had lower fertility levels than women in non-AIDS-affected households in both 1992 and 1995. This pattern was true of women at older ages, in polygamous unions, the widowed and separated, and among the highly educated and the uneducated.

Adolescent↗

PubMed1999

[Mechanism of spontaneous occurrence of tachycardia].

Tachycardias arise from an arrhythmogenic substrate and a trigger factor, an extrasystole, the two factors being under the influence of the autonomic nervous system. The study of the mechanisms of spontaneous initiation of arrhythmias must, therefore, take these three factors and their interactions into account. The frequency dependency of an arrhythmia and the sensitivity of the substrate to the adrenergic system varies with time in a given subject and from one patient to another according to the presence and type of cardiac disease. The mode of initiation of most ventricular tachycardias and the therapeutic consequences may be understood: in some forms of cardiac disease, such as arrhythmogenic right ventricular dysplasia, the increase in heart rate which usually precedes sustained ventricular arrhythmias is only perceptible in mild or recent forms, unlike the more chronic dysplasias. This suggests that the arrhythmogenic substrate becomes more sensitive to catecholamines with time, and therefore requires smaller changes in sympathetic tone in order to be expressed (adrenergic paradox). Heart rate changes accompany modifications of sinus variability. Holter monitoring has shown, and this has been confirmed by recordings obtained from patients with implanted automatic defibrillators, that global sinus variability decreases before the initiation of a ventricular arrhythmia. Studies of the dynamics of ventricular repolarisation should also confirm the changes of QT frequency-dependency. The analysis of the initiation of arrhythmias would only have an academic interest if this was limited to a purely descriptive exercise. It is one of the best means of understanding arrhythmias and their therapeutic implications. The development of computerised methods of analysis of Holter monitoring should lead to further progress in this field.

Cardiomegaly↗

PubMed1987

[Studies on the interrelation of fetal heart rate change, placental findings and fetal outcome].

The relation between antepartum fetal heart rate (FHR) non stress test (NST), maternal serum estriol, intrapartum FHR change, birth weight, placental findings and Apgar score were studied in 168 normal gestations and 36 high-risk pregnancies including 25 EPH-gestosis cases. The frequency of placental infarcts was higher in severe gestosis than in other high-risk pregnancies and normal gestation. Abnormal NST was more frequent in high-risk pregnancy than normal. Light for date (LFD) infants were more numerous in high-risk pregnancy than normal, and also frequent in the cases of placental infarcts. Particularly in high-risk pregnancy patients with abnormal NST and placental infarcts, 3 out of 5 showed LFD infants. Intrapartum fetal distress was more common in the cases of abnormal NST than normal. The five minute Apgar score was lower in the patients with abnormal NST and in the cases of placental infarcts than normal. The placental infarct ratio was higher in high-risk pregnancies with abnormal NST than normal. The maternal serum estriol level was not changed in cases of high-risk pregnancy, abnormal NST or placental infarcts when compared to normal gestation. The cases of succeeding fetal death, however, showed a low serum estriol level. In conclusion, antepartum abnormal NST suggests severe placental dysfunction caused by its infarcts and the prognosis is poor in patients with high-risk pregnancies, particularly EPH-gestosis. Coping with abnormal antepartum NST is regarded as important in fetal management.

Apgar Score↗

PubMed1996

[Increasing use of cesarean section, even in developing countries].

At Kaziba hospital in rural Zaire, the frequency of deliveries by Caesarean section rose from 6.2% in 1971 to 12% in 1992, and the fraction of repeated sections rose from 17% to 49%. During the same period, the overall maternal mortality decreased from 0.3% to 0.12%, and deaths connected with Caesarean section from 3.2% to 0.7%, but still the risk of dying remained 13 times higher for births by Caesarean section compared with vaginal deliveries. The frequency of vacuum deliveries was halved during the period, and mean birth weight decreased by about 100 g. Perinatal mortality remained at about 2%. Among 760 Caesarean sections performed in the years 1991 and 1992, 93% were emergency cases. Spinal anesthesia was used in 97%, and blood transfusion was given to 4% of the women. The main indications were mechanical (30%), previous Caesarean section (20%), foetal asphyxia (19%), and suspected uterine rupture (10%). Uterine rupture was verified in 37 cases (4.9%), of which 27 were Caesarean scar ruptures. 259 of the operations were performed by a nurse or a dentist. Operations carried out by persons other than physicians were complicated by wound infections at a higher rate (20.8%) than those carried out by experienced doctors (11.2%). In areas with a poorly developed health system, a high rate of Caesarean section represents a hazard to maternal health. The need for knowledge about alternative methods like vaginal extraction, symphyseotomy and active management of labour is underlined.

Cesarean Section↗

PubMed1996

Diagnosis and treatment of superficial bladder cancer: an update.

It is expected that approximately 50,500 new cases of bladder cancer will be diagnosed in 1995. In addition, approximately 10,000 people are expected to die of this disease during the year. An 11% increase in incidence observed from 1957 to 1987 was accompanied by a 19.4% decrease in the death rate in American males. This rate change may be attributable to stage migration to more localized disease as well as increased survival owing to improved treatment. Transurethral resection is standard first-line treatment for transitional cell carcinoma of the bladder. Intravesical therapy with cytotoxic agents or immunomodulators has become an important element in the management of patients with superficial bladder cancer at risk for disease recurrence and progression. Study results confirm the efficacy of both mitomycin and bacille Calmette-Guérin when administered intravesically. Comparative studies of these two agents are warranted to further clarify their respective roles in the prophylaxis of recurrences of superficial bladder cancer. Studies should enroll large numbers of patients, particularly those with high-grade lesions at significant risk of recurrence and progression. Current research involves evaluation methods of optimizing the efficacy of intravesical chemotherapy. High drug concentrations, hyperthermia, and combination modalities are a few new avenues being studied. In addition, new drugs like bropirimine, interferons, mycobacteria-associated antigens, and keyhole-limpet hemocyanin are being explored.

Adjuvants, Immunologic↗