[A comparative evaluation of fixed dentures with metal ceramic and titanium nitride coatings].

The authors emphasize that cermet and metal plastic dentures should be widely used in practical orthodontics. They suggest new approaches to the selection of indications for the tooth preparation to cast dentures in view of the necessity of coating these dentures. The shortcomings of dentures with titanium nitride coating are disclosed.


[The determination of the area and closeness of the fit of the dental arches].

A device and method for estimation of the area and tightness of the dentition contact are described, based on the photoelectric effect. Characteristics of the material used to obtain the occlusion impression are presented.


[A chewing gum with mineral additives].

Finely dispersed hen egg shell was added to a new chewing gum as a mineral component. The studies carried out in 28 schoolchildren have shown that 15 min chewing of this gum results in a marked elevation of salivary Ca levels and in improvement of the hygienic status of the oral cavity. This fact recommends this chewing gum as an additional means for care of the oral cavity for both hygienic purposes and for improving the mineralizing potential of the saliva.


[The clinico-experimental validation of the use of low-intensity laser radiation for the treatment of exacerbated recurrent herpetic stomatitis in children].

Experimental data are presented, validating the use of low-intensity laser irradiation at a wave length of 633 nm for the treatment of chronic recurrent herpetic stomatitis. Clinical trials were carried out in 167 children. Laser exposure with the optimal stimulating parameters was found to be an effective means for the treatment of children suffering from this condition.


[The dynamics of the basic autonomic body functions of patients during a consultation with the orthodontist].

Vegetotropic effects of several psychotropic drugs were studied, based on the time course of vegetative symptoms. Computer-based automated diagnostic complex, developed by the author, was used in the study. A total of 261 patients aged 17 to 61, afraid of stomatologic manipulations, were examined. Psychotropic drugs normalized the principal vegetative functions of the body. This fact confirms not only the psychotropic, but the vegetotropic effect of these drugs.


[AN experimental study of the action of industrial aerosols and toxic gases on dental status].

Experiments with white rats have demonstrated that exposure to adverse factors of industrial environment (aerosols and gases) results in increased incidence of caries (by 30-40%) and in a more grave course of the carious process. These changes course along with disorders of the metabolic processes, of the blood and salivary enzymatic systems first of all.


[The comparative characteristics of the parameters of the temporomandibular joint and skull in children with bite anomalies].

The authors compare the mean values of 5 parameters of the temporomandibular joint and 19 skull parameters, analyzing 155 tomograms of the joint and 246 teleroentgenograms of the head of children with sagittal and vertical occlusion abnormalities during change of teeth and in permanent occlusion. This comparison has revealed a relationship between the parameters of the temporomandibular joint and the skull. The correlations were the most marked between the height of the mandibular head, height of the mandibular fossa, on the one hand, and anterosuperior and total posterior heights of the face, length of mandibular body and height of its branch, on the other hand. The longitudinal size of the mandibular head corresponded to the longitudinal size of the base of the skull, maxilla, and the angle of the skull base inclination. Complete harmony between the longitudinal and vertical sizes of the skull is observed after change of teeth.


Studies on anabolic steroids. 9. Tertiary sulfates of anabolic 17 alpha-methyl steroids: synthesis and rearrangement.

A simple and convenient method has been developed to prepare sulfates of anabolic 17 beta-hydroxy-17 alpha-methyl steroids. The sulfates of methandienone, 17 alpha-methyltestosterone, mestanolone, oxandrolone, and stanozolol were prepared. Different A-ring functions were not affected under the sulfation condition. The buffered hydrolyses of these sulfates provided the 17-epimers of the original steroids and 17,17-dimethyl-18-nor-13(14)-ene steroids, presumably via the 17-carbocations.


Androgen metabolism assessment by routine gas chromatography/mass spectrometry profiling of plasma steroids: Part 1, Unconjugated steroids.

Using gas chromatography/mass spectrometry we have developed a method for the simultaneous determination of six plasma steroids: testosterone, 4-androstenedione, 17 alpha-hydroxyprogesterone, 5 alpha-androstane-3 alpha,17 beta-diol, 5 alpha-dihydrotestosterone, and dehydroepiandrosterone. For each analyte, a deuterium-labeled internal standard was used for quantification. Due to the high isotopic purity of our standards, no complex corrections for isotope contributions were necessary. The procedure provides a sensitive and specific technique with good accuracy and precision.


[Clinical and technical measures to improve the fit of whole-cast fixed dentures to the denture bed].

Basing on the literature data and their clinical experience, the authors analyze the following factors influencing the union of whole-cast permanent dentures and denture bed: shape of the prepared tooth, use of various types of benches, presence of free space for cement, compensation for the alloy shrinkage, simplification of placing the dentures by perforating the crowns, use of vibration, lesser volumes of cement put into the crown, and various methods of transferring the masticatory pressure to the denture over the course of denture fixation. Practical significance of these factors is estimated.


Hepatic metabolism of 3-oxoandrost-4-ene-17 beta-carboxylic acid in the adult rat: formation of carboxyl-linked glucuronides both in vivo and in vitro.

The hepatic metabolism of 3-oxoandrost-4-ene-17 beta-carboxylic acid (etienic acid), a probable acidic catabolite of deoxycorticosterone, was investigated using rats prepared with an external biliary fistula. Metabolic products were identified by GC-MS after hydrolysis with beta-glucuronidase and by proton nuclear magnetic resonance after chromatographic purification of protected glucuronides. About 80% of the injected dose was secreted into bile in 20 hours. Three fully reduced etianic acids (3 alpha-hydroxy-5 alpha-, 3 beta-hydroxy-5 alpha-, 3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acids) were identified as were several of their di- and trihydroxylated congeners. Glucuronides of these reduced and/or hydroxylated metabolites constituted over half of the recovered dose, with carboxyl-linked glucuronides predominating over 3-hydroxyl-linked glucuronides. The mode of glucuronidation correlated well with the ability of liver microsomes to form the corresponding compounds in vitro from the set of four 3,5-diastereomeric etianic acids.


Influence of glucocorticoid on the metabolism of aldosterone in the isolated perfused rat liver and kidney.

The effect of glucocorticoid deficiency and excess on the extraadrenal metabolism of D-[4-14C]aldosterone (at 4 nM) was studied by radioimmunoassay and by high-performance liquid chromatography in the isolated perfused liver and kidney of adult Wistar rats. Bilateral adrenalectomy was performed 3 weeks before experiments. In nonadrenalectomized rats, 0.3 mg/kg/day dexamethasone was continuously infused subcutaneously for 1 week before experiments. Adrenalectomy did not affect hepatic or renal metabolism of aldosterone. Dexamethasone treatment did not change the renal handling of aldosterone. However, the hepatic clearance of aldosterone was 19% lower (P less than 0.05) in livers of dexamethasone treated rats than in livers of normal rats. After 5 minutes, perfusate [4-14C]aldosterone metabolites were lower in livers of dexamethasone-treated than in livers of normal rats (P less than 0.05). Similar perfusate levels were then obtained. Radiometabolite peaks with similar relative retention times were found in the hepatic perfusate of all groups. However, the ratio between circulating polar metabolites of aldosterone and the metabolites less polar than tetrahydroaldosterone, after 5 and 15 minutes, was highest in livers of dexamethasone-treated rats. Biliary elimination of 14C was similar in all groups. Significant amounts of conjugated tetrahydroaldosterone were only excreted in the bile of dexamethasone-treated rats. In conclusion, glucocorticoid excess reduced the hepatic clearance of aldosterone and changed the pattern of the hepatic metabolites of aldosterone both in circulation and in bile.


Two new 9,11-secosterols from the marine sponge Spongia officinalis. Synthesis of 9,11-seco-3 beta,6 alpha,11-trihydroxy-5 alpha-cholest-7-en-9-one.

Two new 9,11-secosterol, 9,11-seco-3 beta,6 alpha,11-trihydroxy-5 alpha-cholest-7-en-9-one (2) and 9,11-seco-3 beta,6 alpha,11-trihydroxy-24- methylene-5 alpha-cholest-7-en-9-one (3), have been isolated from the marine sponge Spongia officinalis and their structures elucidated by analysis of spectral data including 1H nuclear magnetic resonance correlation spectroscopy (COSY) experiments. Partial synthesis of 2 starting from 3 beta,6 alpha-dihydroxy-9-oxo-9,11-seco-5 alpha-cholest-7-en-11- al (1) confirmed the structure assignment.


Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin.

The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin. We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine. Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin. These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.


Hematogenous factors and prediction of delayed ischemic deficit after subarachnoid hemorrhage.

Delayed ischemic deficits contribute to the high morbidity and mortality rates associated with subarachnoid hemorrhage. We evaluated the potential usefulness of measuring coagulation and hemorheological variables and cardiolipin antibodies for prediction of delayed ischemic deficit after subarachnoid hemorrhage. Consecutive patients with subarachnoid hemorrhage were studied. Coagulation and hemorheological variables and cardiolipin antibodies were measured on admission, within 7 days of subarachnoid hemorrhage. A subset of patients was studied on admission and at two subsequent occasions. Sixty-nine patients were studied. Sixty-one of these were without clinical manifestations of vasospasm at admission, and 16 developed delayed ischemic deficit during their hospitalization. None of the laboratory variables measured were significantly different between patients with or without later development of delayed ischemic deficit. Elevation of the fibrin fragment D-dimer was found in the group of eight patients admitted with ischemic symptoms and in 49% (34 of 69) of all patients, but this was not associated with delayed ischemic deficit. Sixteen patients were studied on three occasions; this group showed a significant decrease in hematocrit, an increased white blood cell count, and no change in fibrinogen concentration. Fibrin D-dimer levels rose significantly after surgery (from 5.01 +/- 0.69 to 5.53 +/- 0.58 ln-ng/ml, p less than 0.025) and after onset of delayed ischemic deficit (from 4.71 +/- 0.64 to 5.84 +/- 0.34 ln-ng/ml, p less than 0.01). Hemostatic measurements, hemorheological variables, and cardiolipin immunoreactivity did not predict delayed ischemic deficit in this population.


Stroke incidence rates were unchanged, while fatality rates declined, during 1971-1987 in Göteborg, Sweden.

Stroke risk factors have been shown to change with time in several places; simultaneously, stroke incidence rates have increased in some and decreased in other places. In Göteborg, Sweden, cardiovascular epidemiological research has included stroke registration since 1971. From these data on stroke, incidence and fatality rates from a 17-year period are given. During the period 1971-1987 all cases of stroke occurring in people aged 15-65 years in the city of Göteborg were uniformly recorded, with an estimated case detection rate of 90% or more. Age-adjusted incidence rates of first-ever stroke by sex did not change during the period. Age-specific rates and rates for individual types of stroke (subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral infarction-unspecified stroke combined) were also largely unchanged. A slight increase in the incidence rate of intracerebral hemorrhage may be due to better detection after computed tomography came into use in 1976. Stroke fatality rates declined through the whole period in both sexes and all age groups, markedly so for intracerebral hemorrhage and subarachnoid hemorrhage. This conforms with vital statistics for Göteborg and for Sweden of declining stroke mortality during the period. The decline in stroke fatality rates may be related to decreases in smoking habits and blood pressure together with an increase in the percentage of people on antihypertensive treatment among middle-aged men, and to some extent even middle-aged women, reported from the same population. Why stroke incidence rates did not decline concomitantly is unexplained.


Impact of unruptured intracranial aneurysms on public health in the United States.

Unruptured intracranial aneurysms constitute a significant public health problem that has not been quantified. The purpose of this study is to document the magnitude of this problem in the United States. National Hospital Discharge Survey data from 1979, 1984, and 1989 served as the basis for calculating patient numbers and frequency distributions. Cost estimates included the direct costs of hospitalization and surgery for those who had surgery, disability and lost income from morbidity, and lost income from mortality. The estimated lifetime cost (including hospitalization, surgery, morbidity, and mortality) for annual cases of patients hospitalized with unruptured intracranial aneurysms in the United States is $522,500,000 compared with $1,755,600,000 for patients with aneurysmal subarachnoid hemorrhage. These data underscore the need to better understand unruptured intracranial aneurysm as a risk factor for subarachnoid hemorrhage, to define other subarachnoid hemorrhage risk factors, and to optimize the management of patients with these conditions.


Circadian rhythmicity of stroke onset. Intracerebral and subarachnoid hemorrhage.

Our purpose was to describe and further understand the determinants of the time of onset of parenchymatous intracerebral hemorrhage and subarachnoid hemorrhage in patients enrolled in the Stroke Data Bank. We analyzed the observed times of onset of intracerebral hemorrhage (n = 237 patients) and subarachnoid hemorrhage (n = 243 patients) compared with expected times of onset if the probability of onset was constant across all time intervals. We also analyzed the role of clinical features (if any) in explaining the findings. For intracerebral hemorrhage, 52.5% of patients reported onset times between 0600 hours and 1400 hours, with peak onset between 1000 and 1200 hours (chi 2 = 62.94, df = 11, p less than 0.001). Patients with subarachnoid hemorrhage were more likely to lack a history of hypertension compared with patients who had intracerebral hemorrhage (chi 2 = 23.3, df = 1, p less than 0.001). Patients with subarachnoid hemorrhage were more likely to have more uniform onset time throughout the day (chi 2 = 12.92, df = 7, p = 0.074). However, subarachnoid hemorrhage patients with a history of hypertension were more likely to have peak onset times in mid-to-late morning compared with patients without such a history (chi 2 = 35.25, df = 10, p less than 0.001). The nonuniformity of onset times for intracerebral hemorrhage persisted even if patients with unknown onset times were treated as through their onset times were randomly distributed between 0000 and 0800 hours. Seasonal periodicity and the relation between initial systolic or diastolic blood pressure and time of onset for either type of hemorrhage were not observed. Our data suggest that the time of onset for both intracerebral hemorrhage and subarachnoid hemorrhage patients with a history of hypertension is similar to the diurnal variation in blood pressure.


Assessment of intracranial hemodynamics in sleep apnea syndrome.

Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages. A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome. Increases in mean flow velocity of 19-219% and in blood pressure of 12.5-83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2). The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels.


Leukoaraiosis in relation to prognosis for patients with lacunar infarction.

Close relations between leukoaraiosis detected by computed tomography or magnetic resonance imaging and stroke, particularly lacunar infarction, have been reported. We studied whether leukoaraiosis is related to long-term prognosis for patients with lacunar infarction. We examined monthly 215 patients with lacunar infarction after their first stroke. They comprised 95 patients with leukoaraiosis disclosed by computed tomography on admission (58 men and 37 women; mean age, 71.3 +/- 9.0 years) and 120 patients without leukoaraiosis (81 men and 39 women; mean age, 65.5 +/- 8.9 years). These patients had no previous history of either stroke or obvious dementia before their index stroke. We compared the prognosis with and without leukoaraiosis based on analysis of recurrent stroke, survival, and the prevalence of dementia and rate of dependence in activities of daily living. Life table analysis revealed that the recurrent stroke rate was significantly higher in the patients with leukoaraiosis than in those without it (p = 0.004). The prevalence of dementia and rate of dependence in activities of daily living both 1 month after the index stroke and at the end of the follow-up period were significantly higher in the patients with leukoaraiosis (all parameters, P less than 0.001). Their survival rate was significantly lower than in those not suffering from leukoaraiosis (p = 0.012). Significant differences in these comparisons were also observed after matching for age and sex. The presence of leukoaraiosis as identified by computed tomography indicates a poor prognosis for patients with lacunar infarction.


Relation between middle cerebral artery blood flow velocity and stump pressure during carotid endarterectomy.

Many patient monitoring techniques have been used for detecting cerebral hypoperfusion during carotid endarterectomy. We compared middle cerebral artery blood flow velocities with carotid artery stump pressures to evaluate the indications for common carotid artery cross-clamp shunting and the probable hemodynamic causes of cerebrovascular complications. Blood flow velocities were monitored with transcranial Doppler ultrasound and carotid stump pressures were measured at the time of common carotid artery cross-clamping during 97 carotid endarterectomy procedures. Stump pressures measured with the gauge zero reference at the common carotid artery level were correlated with the percentage change of velocities. Middle cerebral artery blood flow velocities usually decreased upon common carotid artery cross-clamping, depending on collateral availability and the autoregulation response. The best fit of the data was to an exponential function concave to the pressure axis, with velocity as a percentage of the pre-cross-clamp value reaching zero at 15 mm Hg stump pressure (r = 0.85 and p less than 0.001). There is a less critical margin of error with percentage middle cerebral artery blood flow velocity decreases than with stump pressure measurements. This relation establishes changes in middle cerebral artery blood flow velocities as a reliable parameter for judging the effects of carotid cross-clamping on cerebral blood flow and providing an excellent indicator as to the necessity for shunting.


Anosognosia in patients with cerebrovascular lesions. A study of causative factors.

Psychological and biological hypotheses have been proposed to explain anosognosia. We correlated the presence of anosognosia with the presence and severity of psychiatric disturbances, neglect, intellectual impairments, and computed tomographic evidence of lesion size, location, and measurements of brain atrophy. A series of 80 patients with acute stroke were assessed using a battery of psychiatric and neuropsychological tests and computed tomography. There were five main findings. First, 27 (28%) of the 96 patients originally screened showed anosognosia. Second, patients with anosognosia had significantly higher frequencies of hemispatial neglect and related phenomena, as well as deficits in recognizing facial emotions and in receptive prosody. Third, depression was equally frequent among patients with and without anosognosia. Fourth, patients with anosognosia had a significantly higher frequency of right hemisphere lesions, primarily involving the temporoparietal junction, thalamus, and basal ganglia. Fifth, patients with anosognosia showed significantly more subcortical brain atrophy, primarily involving the frontal white matter and diencephalic areas. The present study demonstrates that anosognosia does not "protect" stroke patients from depressive feelings; rather, it represents arousal-attentional disorders after lesions in specific areas of the right hemisphere in nonaphasic patients with preexisting subcortical atrophy.


Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs.

Mild cerebral hypothermia (34 degrees C) induced immediately after cardiac arrest improves outcome. Deep postarrest hypothermia (15 degrees C) has not been studied. We used our dog model of normothermic ventricular fibrillation (no blood flow) of 12.5 minutes, reperfusion by brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 72 hours. Head surface cooling and bypass cooling were performed from start of reperfusion to 1 hour. Five groups of six dogs each were compared: group I, normothermic controls; group II, deep hypothermia (15 degrees C); group III, moderate hypothermia (30 degrees C); group IV, mild hypothermia (34 degrees C); and group V, mild hypothermia with head surface cooling begun during no flow. In control group I, five dogs remained comatose (overall performance category [OPC] 4) and one severely disabled (OPC 3). In group II, four dogs achieved OPC 4 and two dogs OPC 3 (NS versus group I). Compared with group I, OPCs were better in group III (p less than 0.05), group IV (p less than 0.05), and group V (p less than 0.05). Neurological deficit scores were also better in groups III, IV, and V than in groups I or II (p less than 0.05). Total brain histological damage scores were better in group III (p = 0.02), group IV (p = 0.06), and group V (p less than 0.05) than in group I. In group II, OPC and neurological deficit scores were the same and histological damage scores numerically worse than in group I and all were worse than in groups III, IV, and V (p less than 0.05). Cardiovascular complications and myocardial morphological damage in groups II and III were worse than in groups I, IV, and V (p less than 0.05). Mild or moderate cerebral hypothermia induced immediately after cardiac arrest improves cerebral outcome, more likely when initiated during arrest, whereas deep postarrest hypothermia can worsen cerebral and cardiac outcome.


Effects of ischemia duration on neurological outcome, CA1 histopathology, and nonmatching to sample learning in monkeys.

Male cynomolgus monkeys (n = 10) were subjected to varying durations of global cerebral ischemia to determine the relation between dose (ischemic duration) and response (outcome). Each monkey was anesthetized with halothane, and global cerebral ischemia was produced by a neck tourniquet and trimethaphan-induced hypotension. The animal was subjected to 3 (n = 3), 9 (n = 3), or 12 (n = 4) minutes of ischemia. Neurological examinations were performed daily for 30 days or until the monkey was neurologically normal. Approximately 1 month after ischemia, the animal was evaluated for evidence of neurobehavioral abnormalities with the nonmatching to sample test. When testing was complete, the monkey was killed with an overdose of pentobarbital and the brain perfused with formalin and removed for histopathologic analysis, with particular attention devoted to the hippocampal CA1 region. Monkeys subjected to 3 or 9 minutes of ischemia were neurologically normal (except for a very mild injury in one 9-minute animal) immediately after ischemia and had normal CA1 histology. Monkeys subjected to 12 minutes of ischemia were grossly abnormal neurologically after ischemia, but two of the four animals made a complete recovery (neurological deficit score of 0) by 30 days. Monkeys subjected to 12 minutes of ischemia had mild damage in the CA1 region, with all other brain regions appearing normal. None of the animals had demonstrable decrements in neurobehavioral function as measured by the nonmatching to sample test. We conclude that neurobehavioral testing after global cerebral ischemia in primates is feasible, but the ischemic time necessary to produce CA1 damage that could potentially be quantified antemortem with the nonmatching to sample test is greater than 12 minutes in cynomolgus monkeys and may produce temporary severe gross neurological abnormalities as well.


Mechanism of cerebral blood flow augmentation by hemodilution in rabbits.

Hemodilution is known to increase cerebral blood flow, but it is not known whether the increase in flow is a direct result of a decrease in viscosity or whether it may be due to compensatory vasodilatation in response to the decrease in oxygen carrying capacity that results from hemodilution. This study is designed to investigate this question. Changes in regional cerebral blood flow were studied in normal and ischemic brains of 15 and 18 rabbits, respectively. In one group of rabbits graded hemodilution was used to reduce arterial oxygen content progressively in stages; in the second group the arterial oxygen content was reduced in similar stages by progressively larger reductions in the concentration of inspired oxygen (hypoxic hypoxia). In the ischemic animals focal ischemia was produced by embolic occlusion of the right middle cerebral artery. In the normal rabbits, hypoxic hypoxia and hemodilution resulted in similar progressive increases in cerebral blood flow as arterial oxygen content fell. In the ischemic animals, there was a significant fall in cerebral blood flow in the ischemic region in all groups after arterial occlusion. Hemodilution resulted in a progressive increase in cerebral blood flow in both ischemic and nonischemic regions. With hypoxic hypoxia, however, cerebral blood flow in the ischemic region showed no increase or a slight decrease. Even though hypoxic hypoxia results in a marked increase in cerebral blood flow in normal brain, it does not significantly change cerebral blood flow in ischemic brain. In contrast, hemodilution resulting in a comparable degree of hypoxemia is capable of significantly increasing cerebral blood flow in ischemic brain. Therefore, the mechanism of blood flow augmentation by hemodilution in ischemic brain is probably related to a direct hemorheologic effect rather than to the resulting hypoxemia.


Tirilazad mesylate does not improve early cerebral metabolic recovery following compression ischemia in dogs.

Tirilazad mesylate (U74006F) has been reported to improve recovery following cerebral ischemia. We conducted a randomized blinded study to determine if the drug would improve immediate metabolic recovery after complete cerebral compression ischemia. Mongrel dogs were anesthetized with pentobarbital and fentanyl and treated with either vehicle (citrate buffer, n = 8) or tirilazad (1.5 mg/kg i.v. plus 0.18 mg/kg/hr, n = 8). Normothermic complete cerebral compression ischemia was produced for 12 minutes by lateral ventricular fluid infusion to raise intracranial pressure above systolic arterial pressure. Cerebral high-energy phosphate concentrations and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Cerebral blood flow was measured with radiolabeled microspheres, and oxygen consumption was calculated from sagittal sinus blood samples. Somatosensory evoked potentials were measured throughout the experiment. During ischemia, both groups demonstrated complete loss of high-energy phosphates and a fall in intracellular pH (vehicle, 5.76 +/- 0.23; tirilazad, 5.79 +/- 0.26; mean +/- SEM). At 180 minutes of reperfusion, there were no differences between groups in recovery of intracellular pH (vehicle, 6.89 +/- 0.07; tirilazad, 6.88 +/- 0.18), phosphocreatine concentration (vehicle, 89 +/- 16%; tirilazad, 94 +/- 24% of baseline value), oxygen consumption (vehicle, 2.6 +/- 0.2 ml/min/100 g; tirilazad, 1.8 +/- 0.5 ml/min/100 g), or somatosensory evoked potential amplitude (vehicle, 11 +/- 6%; tirilazad, 7 +/- 4% of baseline value). Forebrain blood flow fell below baseline levels at 180 minutes of reperfusion in the tirilazad-treated animals but not in the vehicle-treated dogs (vehicle, 28 +/- 4 ml/min/100 g; tirilazad, 18 +/- 5 ml/min/100 g). We conclude that tirilazad pretreatment does not improve immediate metabolic recovery 3 hours following 12 minutes of normothermic complete ischemia produced by cerebral compression.


Effect of diabetes mellitus on flow-mediated and endothelium-dependent dilatation of the rat basilar artery.

Diabetes mellitus may impair endothelium-dependent responses in cerebral arterioles. The basilar artery dilates in response to increases in blood flow. The goal of this study was to examine effects of diabetes mellitus on "flow-mediated" and endothelium-dependent dilatation of the basilar artery. Diabetes was induced in rats with 50 mg/kg streptozotocin. Six months later, vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in anesthetized rats under baseline conditions and during occlusion of the carotid arteries. Changes in vessel diameter were also measured during topical application of acetylcholine and sodium nitroprusside. With aortic pressure maintained at baseline levels, blood flow velocity through the basilar artery increased similarly in control and diabetic rats during unilateral common carotid artery occlusion and during bilateral occlusion. In control and diabetic rats, diameter of the basilar artery increased by 10 +/- 2% and 10 +/- 4% during unilateral occlusion and by 27 +/- 5% and 31 +/- 4% during bilateral occlusion, respectively. Thus, diabetes did not impair flow-mediated dilatation of the basilar artery. In contrast, dilatation in response to 10(-5) M topical acetylcholine was less in diabetic rats (13 +/- 2%) than in control rats (45 +/- 8%) (p less than 0.05). Dilator responses to nitroprusside were not impaired by diabetes. The findings suggest that diabetes produces impairment of endothelium-dependent responses to acetylcholine, but not flow-mediated dilatation, in the basilar artery.


Effect of diabetes mellitus on responses of the basilar artery in rats to products released by platelets.

Aggregation and adherence of platelets to vascular endothelium are increased during diabetes mellitus, and thus responses of cerebral arteries to products released by platelets may have important implications for the pathogenesis of stroke during diabetes. The goal of this study was to determine whether responses of the basilar artery to products released by platelets are altered during diabetes. A craniotomy was performed over the ventral medulla to expose the basilar artery. Diameter of the basilar artery was measured using intravital microscopy in nondiabetic and diabetic (50-60 mg/kg i.p. streptozotocin) rats in response to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619. Topical application of 10 and 100 microM adenosine 5'-diphosphate produced only minimal changes in diameter of the basilar artery that were similar in nondiabetic and diabetic rats (p greater than 0.05). At 0.01, 0.1, and 1.0 microM serotonin produced dose-related constriction of the basilar artery that was similar in nondiabetic and diabetic rats (p greater than 0.05). At 0.1 and 1.0 microM U-46619 also produced similar dose-related constriction of the basilar artery in nondiabetic and diabetic rats (p greater than 0.05). These findings suggest that responses of the basilar artery to products released by platelets are not altered by diabetes mellitus. Thus, it does not appear that alterations in reactivity of the basilar artery to products released by platelets contribute to the pathogenesis of stroke during diabetes.


Glucose-associated alterations in ischemic brain metabolism of neonatal piglets.

During global brain ischemia or hypoxia-ischemia in adults, hyperglycemia is deleterious to the brain. In contrast, similar adverse effects have not been found in neonatal animals. This investigation examined neonatal piglets to determine if there were specific alterations of ischemic brain metabolism associated with different systemic glucose concentrations and to potentially clarify the effects of hyperglycemia during ischemia in neonates. Two groups of animals (n = 12 in each group) were studied during partial ischemia to compare the effects of hyperglycemia (plasma glucose concentration, 258 +/- 97 mg% [mean +/- SD]) with modest hypoglycemia (plasma glucose concentration, 62 +/- 23 mg%). A broad spectrum of cerebral blood flow reduction was achieved by combining inflation of a cervical pressure cuff with varying degrees of hemorrhagic hypotension. High-energy phosphorylated metabolites, intracellular pH, and cerebral blood flow were simultaneously measured using a magnetic resonance spectroscopic technique. Brain metabolic variables (beta-ATP, inorganic phosphorus, phosphocreatine, intracellular pH) were plotted as a function of blood flow reduction during partial ischemia for each group. During ischemia values of cerebral blood flow were comparably distributed between groups and ranged from 15% to 110% of those of control. At a given reduction of cerebral blood flow, hyperglycemic piglets maintained a higher concentration of beta-ATP (p = 0.011) and had a smaller increase in inorganic phosphorus (p less than 0.001). At cerebral blood flow less than 50% of control, the intracellular pH of piglets with modest hypoglycemia during partial ischemia was never reduced to less than 6.46, whereas intracellular pH fell as low as 5.97 for hyperglycemic animals. ATP preservation may account for the differing effects of glucose during ischemia in neonates compared with adults, provided that the accentuated brain acidosis is not deleterious to neonatal brain tissue.


Effect of lidocaine on somatosensory evoked response and cerebral blood flow after canine cerebral air embolism.

Victims of air embolism often recover rapidly on hyperbaric treatment then deteriorate again, even if hyperbaric treatment is continued. In previous animal experiments, lidocaine has been shown to improve recovery of somatosensory evoked response amplitude after air embolism. However, animals in these experiments rarely deteriorated. We have shown that the induction of air embolism and transient hypertension in canines produces deterioration despite hyperbaric treatment, and we decided to test the effect of lidocaine on somatosensory evoked potential recovery and cerebral blood flow in this model. Dogs were treated with repeated doses of lidocaine or equivalent volumes of saline during hyperbaric therapy after internal carotid air embolism and transient hypertension. The investigators were unaware of treatment group assignment during the experiments. The amplitude of the median nerve somatosensory evoked potential and cerebral blood flow measured with carbon-14-labeled iodoantipyrine autoradiography were used to assess effect of therapy. Lidocaine-treated dogs recovered 60 +/- 10% (mean +/- 95% confidence limits) of the baseline somatosensory evoked potential amplitude 220 minutes after air embolism; saline-treated dogs recovered 32 +/- 10% (a significant difference at p less than 0.01). Lidocaine-treated dogs also had higher cerebral blood flow values than saline-treated dogs 220 minutes after air embolism. Lidocaine ameliorated the delayed deterioration of evoked potential associated with air embolism and hypertension in this canine model. The improved cerebral blood flow may be a mechanism of action of lidocaine or an associated effect of improved neuronal survival.


Endothelium-derived relaxing factor modulates noradrenergic constriction of cerebral arterioles in rabbits.

Cerebral arterioles are relatively unresponsive to norepinephrine. We tested the hypothesis that release of endothelium-derived relaxing factor is stimulated by norepinephrine and attenuates adrenergic constriction of pial arterioles. In seven anesthetized New Zealand White rabbits, diameter of pial arterioles was measured through a cranial window. Responses to topical application of norepinephrine and arginine vasopressin were examined before and during application of NG-nitro-L-arginine, which inhibits synthesis of endothelium-derived relaxing factor. Norepinephrine (10(-6) M) had no effect (0 +/- 3%, mean +/- SE) on arteriolar diameter under basal conditions. Norepinephrine decreased arteriolar diameter by 15 +/- 4% during application of nitro-L-arginine (10(-4) M) (p less than 0.05 versus basal response). L-arginine inhibited the effect of nitro-L-arginine on responses of pial arterioles to norepinephrine. In contrast to norepinephrine, constrictor responses of pial arterioles to vasopressin were not potentiated by nitro-L-arginine. Norepinephrine, but not arginine vasopressin, releases endothelium-derived relaxing factor, which inhibits constrictor responses of cerebral arterioles in rabbits. This mechanism contributes to the finding that cerebral vessels in rabbits are relatively unresponsive to noradrenergic stimuli.


Population pharmacokinetics of gentamicin in premature infants.

The population kinetics of gentamicin were studied in 97 newborn patients with a gestational age ranging between 28 and 43 weeks and a postnatal age ranging between 2 and 30 days undergoing routine therapeutic monitoring of their serum gentamicin levels. The individual kinetic analysis of serum drug levels was performed using a single-compartment model. The clearance and apparent distribution volume were calculated in each patient. The population model employed assumes the existence of residual variability in the serum concentrations and interindividual variability in the pharmacokinetic parameters. The effects of demographic variables on the clearance, distribution volume, and optimum daily dose of gentamicin were established using multiple linear regression. Gestational age is the best predictive variable of the clearance and the optimum dose/day in the whole population studied. In the premature infant patients, the predictive capacity increases with postconceptional age. Weight is a good predictive variable of all of the parameters, especially of the apparent distribution volume in the overall population of newborns. Analysis of the population kinetic behavior and optimum dose/day in each subgroup recommends that the interval of drug administration should be increased, keeping the same dose/day ratio, due to the tendency of the drug to accumulate its long half-life, especially in premature babies.


Maintenance payments for child support in southern Africa: using law to promote family planning.

This article presents some of the legal, social, cultural, and practical constraints facing women who attempt to enforce their right to maintenance (child support) payments in southern Africa. It is based on research by the Women and Law in Southern Africa Trust, a network of women who research women's legal rights in six countries: Botswana, Lesotho, Mozambique, Swaziland, Zambia, and Zimbabwe. Statutes in all countries in the region provide that a man must support his legitimate and illegitimate children; there are, however, weaknesses in the laws on the books. The social and cultural constraints that influence the enforcement of maintenance laws include women's lack of knowledge of the law, attitudes toward child support influenced by customary law, allegations of women's abuse of maintenance payments, financial and practical problems, and fear of physical violence or other forms of retribution. Maintenance laws are relevant to family planning in that if such laws were more effectively enforced, so that the financial burden of children were more equally shared between women and men, men would have a financial stake in controlling their fertility.


Utility of a one-point (3-hour postdose) plasma metabolic ratio as a phenotyping test using metoprolol in two east Asian populations.

We examined the utility of the postdose 3-h plasma metabolic ratio (MR) as a phenotyping method for assessing genetically determined debrisoquine-type oxidation polymorphism after an oral dose of 100 mg of metoprolol tartrate administered to 402 unrelated, healthy, and native East Asian (218 Korean and 184 Japanese) subjects. All of them were phenotyped simultaneously with the reported MR employing urine samples collected during an 8-h postdose period. In the two populations, the distribution histograms and probit plots of log10plasma MRs derived from the metoprolol/alpha-hydroxymetoprolol concentration values indicated a large gap between the extensive and poor metabolizers who were phenotyped by the reported criteria of the 8-h urinary MR. There were statistically significant (p less than 0.001) correlations (rs = 0.688 and 0.810, respectively) between the postdose urinary and plasma MRs in the Korean and Japanese populations. Two poor metabolizers (one each included in the two racial groups) identified according to the 8-h urinary MR gave the greatest plasma MRs (i.e., 549.7 among the Koreans and 150.0 among the Japanese). The results suggest that the one-point, postdose 3-h plasma MR is also useful for the phenotyping purpose of oxidation pharmacogenetic polymorphism of metoprolol, a widely prescribed beta-adrenoceptor blocking drug.


Preceding birth intervals and child survival: searching for pathways of influence.

The importance of the length of preceding birth intervals for the survival chances of young children has been established, but the debate concerning the causal biomedical or behavioral mechanisms continues. This article uses data from 17 Demographic and Health Surveys to investigate the effect of birth intervals on child mortality: Anthropometry of children, recent morbidity of children, and use of health services are examined in addition to child survival data for children born in the five years before the survey. Various methodological approaches are used to investigate the relative importance of the postulated mechanisms linking birth intervals and child survival. Short preceding birth intervals are associated with increased mortality risks in the neonatal period and at 1-6 months of age, and, to a much lesser extent, at 7-23 months of age. The effects of short birth intervals on nutritional status are rather moderate, and there is a weak relationship with lower attendance at prenatal care services. No consistent relationship exists between the length of birth intervals and other health status or health-service utilization variables. The results indicate that prenatal mechanisms are more important than postnatal factors, such as sibling competition, in explaining the causal nature of the birth interval effect.


Subjective side effects of mianserin in relation to plasma concentrations of mianserin and desmethylmianserin.

The main purpose of the present study was to examine the possibility that plasma concentrations of mianserin and its metabolite, desmethylmianserin, might be predicted by recording subjective side effects. In 44 depressed patients, subjective side effects during 3 weeks of treatment with 30 mg of mianserin were evaluated by the UKU Side Effect Rating Scale, and their relationships to plasma concentrations of mianserin and desmethylmianserin were analyzed. There was no significant relationship between plasma concentrations of these compounds and the occurrence of mianserin-induced side effects, except for dryness of mouth during week one. Our study, therefore, suggests that it is difficult to predict plasma concentrations of mianserin and desmethylmianserin based on the occurrence of subjective side effects.


Contraceptive use in Matlab, Bangladesh: the role of gender preference.

Research in several Asian societies has suggested that sons are generally preferred over daughters. The implications of gender preferences for actual fertility behavior have not been adequately investigated, however. This analysis examines the effect of the sex composition of surviving children on the acceptance and discontinuation of contraception in a sample of 3,145 women in Matlab, Bangladesh, who were observed for 60 months. Hazards regression analyses are employed in the analysis. Strong and highly significant effects of gender preference on contraceptive use are observed. The preference is not monotonically son-biased but is moderated toward a balanced composition, because parents desire to have several sons and at least one daughter. These findings suggest that gender preferences, particularly a preference for sons, represent a significant barrier to fertility regulation in rural Bangladesh.


Fertility and contraceptive adoption and discontinuation in rural Kenya.

After a long period of slow progress, the recent uptake of contraceptive use in Kenya has been dramatic. This report describes adoption of a method and method switching and discontinuation among a cohort of married women aged 25-34 in two contrasting rural areas. A retrospective "fertility diary" completed by each woman provided information on spousal separation, reproductive status, and contraceptive use over a period of 46-48 months. Contraceptive prevalence rose rapidly over the period in both areas, with significant net adoption of injectables in both areas and of IUDs in one only. Method discontinuation was concentrated among users of pills, barrier methods, and "natural" methods, and only one-third of all discontinuations were voluntary. The wide differences between the two rural areas in contraceptive prevalence were not totally reflected in recent fertility levels, and the contribution of other proximate determinants of fertility, particularly postpartum amenorrhea and spousal separation, are discussed.


Interaction between fluvoxamine and imipramine/desipramine in four patients.

We describe four patients in whom the addition of fluvoxamine (100 mg/day) to the treatment with imipramine or desipramine (100-150 mg/day) resulted in a dramatic increase in the plasma concentrations of the tricyclic antidepressants associated with adverse effects. These observations indicate that fluvoxamine inhibits both the demethylation of imipramine and, possibly to a lesser extent, the hydroxylation of desipramine. The combination of fluvoxamine with tricyclic antidepressants should be avoided whenever possible.


Estimates of demand for abortion among Soviet immigrants in Israel.

In 1990, more than 185,000 Soviet Jews emigrated to Israel, increasing Israel's population by 4 percent; 148,000 more arrived in 1991. Given the fertility and abortion patterns prevailing among Soviet women in their native country, this article inquires about the short-range expected increase in abortion demand in Israel engendered by this large migratory inflow. Estimation techniques based on the abortion experience of an earlier wave of Soviet-born immigrants in Israel reveal that the increase in requests for abortion brought about by the 1990 immigrants may reach up to 14 percent, and as high as 24 percent for the combined immigration waves of 1990 and 1991. The expanded demand for abortions in Israel engendered by the new Soviet immigrants necessitates an expansion of both family planning services and of the medical committees entitled to grant a legal abortion. A failure in these fields would benefit illegal abortion.


Therapeutic drug monitoring of retinoids.

Retinoids are natural or synthetic compounds related to vitamin A. They are successfully used in the treatment of dermatological disorders. However, one of the limiting factors in the use of retinoids is their huge teratogenic potential. The investigation into the pharmacokinetics and metabolism of retinoids has encountered many difficulties due to lack of suitable techniques to deal with these labile compounds. Because of the teratogenic nature of the retinoids, the sensitivity of the assay is of utmost importance. We report a systematic comparison between two high-performance liquid chromatographic methods used to monitor levels of etretinate and its metabolites acitretin and 13-cis-acitretin in plasma. Our analysis suggests that the column-switching method is superior owing to smaller variability in results and its simplicity. We also describe our therapeutic drug monitoring program for counseling women of reproductive age following etretinate or acitretin exposure. Presently, labeling of etretinate in North America suggests that women should refrain from conception for an undetermined length of time. Assessment of serum concentrations over time is beneficial in defining the length of period to postpone conception.


Bioavailability of labetalol in patients with end-stage renal disease.

The pharmacokinetics and pharmacodynamics of labetalol were assessed after a single oral and intravenous dose in eight patients with end-stage renal disease (ESRD) maintained on chronic hemodialysis, and in eight age-and sex-matched normal volunteers. The mean area under the serum concentration-time curve, volume of distribution, clearance, and terminal elimination half-life values after a single intravenous dose of 0.5 mg/kg of labetalol were not significantly different between ESRD patients and normal volunteers. Similarly, the absolute bioavailability of an oral dose of 200 mg of labetalol was 0.33 in ESRD patients and was not significantly different from that of normal volunteers (0.26). However, a significant decrease in the area under the mean blood pressure-time curve was found after a single oral dose in ESRD patients, which was not observed in normal volunteers. The pharmacokinetics of labetalol were not associated with changes in blood pressure. Thus, when given orally to the ESRD patient, labetalol should be slowly titrated and the blood pressure closely monitored.


Radioimmunoassay for ceronapril, a new angiotensin-converting enzyme inhibitor, and its application to a pharmacokinetic study in healthy male volunteers.

Ceronapril is a member of a new chemical class of angiotensin-converting enzyme inhibitors being developed by The Bristol-Myers Squibb Pharmaceutical Research Institute. A radioimmunoassay (RIA) has been developed for the measurement of ceronapril in biological fluids. The RIA has a range of 0 to 500 ng/ml and has the sensitivity to detect 1.0 ng/ml of ceronapril. Satisfactory zero binding and sensitivity were obtained after a 2-h incubation at room temperature or overnight at 4 degrees C. Separation of the antibody-bound and free radiolabel was achieved by employing polyethylene glycol-goat anti-rabbit gamma-globulin separant. A quantitative recovery of the exogenous analyte was obtained at all concentrations of ceronapril tested. Intraassay coefficients of variance (CV's) were 3.9% and 4.6% for the low and medium controls, respectively. A highly significant statistical correlation between RIA and [14C]TLRC was observed for both plasma and urine samples. Clinical samples from the ascending dosage studies have been analyzed by the ceronapril RIA. The maximum concentration and the area under the plasma concentration-time curve did not increase in a dose-proportional manner for doses above 100 mg.


Tissue concentrations of cefepime in acute cholecystitis patients.

Cefepime is a new broad-spectrum cephalosporin with activity against Staphylococcus, Streptococcus, Pseudomonas, and the Enterobacteriaceae. The purpose of this study was to measure cefepime concentrations in plasma, peritoneal fluid, bile fluid and appendix tissue in patients undergoing elective cholecystectomy. Patients were randomly assigned to receive either cefepime, 2 g intravenously in phosphate buffer (IVPB) q 12 h or gentamicin 1.5 mg/kg IVPB q 8 h plus mezlocillin 4 g IVPB q 6 h. During surgery, gall bladder tissue, plasma, peritoneal fluid, and bile fluid samples were obtained at approximately the same time. Thirty-three patients had data acceptable for analysis. Values are given as mean +/- standard deviation. The mean delta time (defined as the time between the administration of cefepime and the time the samples were obtained) was 8.58 +/- 3.53 h. The values for plasma, peritoneal fluid, bile fluid, and gall bladder tissue concentrations were 7.63 +/- 14.17 micrograms/ml, 5.66 +/- 6.80 micrograms/ml, 15.51 +/- 16.94 micrograms/ml, and 5.36 +/- 6.57 micrograms/gm, respectively. The peritoneal fluid/plasma ratio was 2.10 +/- 2.33, the bile fluid/plasma ratio was 14.44 +/- 31.99, and the gall bladder tissue/plasma ratio was 1.44 +/- 1.82. There was a significant correlation between peritoneal fluid and plasma concentration (r = 0.91, p less than 0.0005), and gall bladder tissue and plasma concentration (r = 0.90, p less than 0.0005). There was no correlation between bile fluid and plasma cefepime concentrations. The minimum inhibitory concentration (MIC) data from previous in vitro studies indicate that cefepime concentrations achieved in this patient population would be adequate against typical biliary tract pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)


Specific enzyme-multiplied immunoassay and fluorescence polarization immunoassay for cyclosporin compared with Cyclotrac [125I]radioimmunoassay.

The analysis of cyclosporin-A (CsA) has proved a valuable adjunct to clinical care of patients who have received organ grafts. The measurement of CsA in whole blood by specific methods has recently taken a new direction with the introduction of a range of rapid methods, including a homogeneous enzyme immunoassay technique (EMIT) and a monoclonal fluorescence polarization immunoassay (FPIA). The present paper compares these two methods with the established Cyclotrac specific [125I]RIA (radioimmunoassay) using both commercial CsA-spiked control material as well as a group of 60 patient specimens (predominantly renal transplants). While each of the new methods showed acceptable precision and accuracy with the commercial quality control material, significant differences were demonstrated with patient specimens, such that FPIA was 12.5% greater than [125I]RIA (p less than 0.0001), which was in turn 5.9% greater than EMIT (p = 0.007). These data suggested that the FPIA may have residual CsA-metabolite interference and that the EMIT method was the most "specific" for parent CsA of the three tested, potentially therefore more comparable to high-performance liquid chromatography (HPLC).


Plasma assay of salbutamol by means of high-performance liquid chromatography with amperometric determination using a loop column for injection of plasma extracts. Application to the evaluation of subcutaneous administration of salbutamol.

An isocratic high-performance liquid chromatography method with amperometric detection for the assay of plasma salbutamol is described. The plasma extract is injected into the chromatographic system via a loop column. This insures the purification of the injected extracts and allows a simple and rapid liquid-solid extraction procedure. The good reliability, as shown by the low limit of detection (0.5 ng/ml) and a precision ranging between 5 and 10%, has permitted the investigation of a new mode of administration of salbutamol using a portable subcutaneous infusion pump. Our results show that subcutaneous administration yields plasma levels comparable with those obtained after usual intravenous doses.


Determination of salivary digoxin with a dry strip immunometric assay.

Analysis of salivary digoxin using a rapid dry chemistry, enzyme-labeled immunometric assay (ELIA) was compared with fluorescence polarization immunoassay (FPIA). Saliva and serum samples were obtained from 40 hospitalized patients who were taking digoxin chronically and from 8 patients just prior to treatment with digoxin. Unstimulated saliva samples were collected from 20 patients; however, saliva volumes from 10 pediatric patients were inadequate to permit analysis by FPIA, and 1 other had unmeasurable concentrations by both methods. Stimulated saliva was collected by having patients chew a small piece of Parafilm for 1-2 min. Salivary digoxin was analyzed using the same procedure recommended for serum digoxin by each manufacturer. There were no significant differences found between ELIA and FPIA determinations of unstimulated or stimulated salivary digoxin, serum digoxin, or saliva/serum concentration ratios. The saliva/serum ratio of the unstimulated group was approximately twice that of the stimulated group (p less than 0.01) by both methods, suggesting that salivary digoxin concentration decreases with increased saliva production rate. Excellent correlations were found between ELIA and FPIA salivary digoxin concentrations and between stimulated saliva and serum concentrations by both assays. Weaker correlations were observed between unstimulated saliva and serum concentrations. There was no evidence of assay interference with either method in eight nondigitalized patients, each taking an average of 6.5 medications. The ELIA appears to provide equivalent results compared with the FPIA for the determination of salivary digoxin concentration. Further investigations are needed before salivary digoxin concentration monitoring can be recommended as an acceptable alternative to serum monitoring.


Determination of plicamycin in plasma by radioimmunoassay.

This article describes a method for the determination of plicamycin in plasma by radioimmunoassay. The anti-plicamycin antibody was produced against a plicamycin-bovine serum albumin conjugate prepared by using diazotized p-aminobenzoic acid as a cross-linker. The radiolabeled ligand, 125I-plicamycin, was prepared by the chloramine-T method. The linear plicamycin concentration range was 7-400 ng/ml. The coefficients of variation for intra- and interday variabilities were 7.5 and 15%, respectively. No interference was observed from either the structurally related chromomycin A or concomitantly used drugs hydroxyurea or allopurinol. With this method of testing, plicamycin levels in plasma could be determined in patients receiving small (0.85-1.0 mg/m2) therapeutic plicamycin doses. Preliminary pharmacokinetic data in humans indicate that the plasma drug disappearance curve was biphasic with a mean elimination half-life of 10.6 +/- 1.7 h, total clearance rate of 11.1 +/- 0.4 ml/min/m2, and area under the plasma drug concentration-time curve of 1,289-1,546 ng-h/ml. This assay method is clinically useful for pharmacokinetic studies of plicamycin and may be helpful in the design of rational therapeutic drug trials.


Haloperidol disposition is dependent on the debrisoquine hydroxylation phenotype: increased plasma levels of the reduced metabolite in poor metabolizers.

We have previously shown that the disposition of haloperidol is decreased in poor (PM) compared to extensive (EM) metabolizers of debrisoquine. We now report that the plasma levels of the reduced metabolite of haloperidol, after a single 2- or 4-mg oral dose of the parent drug, are significantly higher in PM than in EM of debrisoquine. As PM have higher concentrations of haloperidol than EM, more of the reduced metabolite should be formed, since the formation of reduced haloperidol from haloperidol seems to be independent of the debrisoquine hydroxylase (cytochrome P4502D6) activity. Another reason to explain the increased metabolite levels in PM may be a decreased reoxidation of the reduced metabolite to haloperidol, as this reaction is catalyzed by cytochrome P4502D6. A third reason might be that reduced haloperidol is transformed to other metabolites by this enzyme.


[Nutritional status of elderly patients at admission to a general psychiatric hospital. An inventory].

The nutritional status of 121 psychiatric patients over the age of 60 years was examined on admission in a general psychiatric hospital. Before admission all patients were living independently. They were admitted directly from their homes. We found that the older psychiatric patient is evidently at risk for malnutrition. A quarter of the males had, according to the Quetelet's index, a low weight. Half of the males and one third of the females had a thiamin-deficiency, whereas half of all patients showed a deficiency of folic acid. Furthermore, in half of the males and one tenth of the females anaemia was diagnosed. Widowers and to a lesser extent also patients with an organic brain disease or psychotic disturbance ran a greater risk of malnutrition in comparison to their fellow patients. A relation between behaviour, measured by the Nosie (Nursing Observation Scale for Inpatient Evaluation) and the nutritional status was not found.


[Assessment of health status of the elderly. Application of a Dutch version of the MOS scale].

The 'MOS Shortform General Health Survey', a measure for assessing general health, has been used in an elderly population in the Netherlands (N = 354). The 20-item (mail) questionnaire comprises six dimensions or subscales: physical functioning (6 items), role functioning (2), social functioning (1), mental health (5), health perceptions (5) and body pain (1). Our results show reasonable psychometric properties of the subscales (internal reliability, skewness and kurtosis of distribution, correlation between subscales and correlation with other health measures, 8 weeks test-retest reliability), which are comparable to those in the United States in a general patient population. The six subdimensions of the scale together seem to meet the criteria of the stochastic cumulative measurement model (Mokken-type scale). The results show that this instrument gives an opportunity to assess general health in the elderly within just a couple of minutes.


[Consequences of handicaps following a cerebrovascular accident for patient's partner].

What is the influence of stroke on experienced burden, coping and well-being of the patient's spouse? To explore this problem we interviewed 22 spouses, living with their husband or wife at home. Stroke had occurred over 12 months ago. There appeared to be different consequences for the spouse, depending upon the kind of handicap: The physical handicaps in stroke-patients were associated with an increase of household tasks and caregiving, and with diminished opportunities for the spouse to relax. Mental deterioration after stroke was slightly associated with a lower level of well-being in the spouse. Spouses of patients with severely impaired communication had fewer opportunities to relax, reported more deterioration of the marital relationship and showed slightly more depression than spouses of patients with slightly impaired communication.


[Paced addition. A neuropsychological test for assessment of divided attention].

The Pasat (Paced auditory serial addition task) is a test requiring addition of simple digits presented auditorily in several series of a successively higher pace of presentation. The task reflects the capacity for divided attention, is a measure of information processing speed and has appeared to be sensitive to minor attention deficits. We made a Dutch version characterized by longer time intervals between digits, for use in a study among (altogether 130) middle-aged and elderly persons. This modified version was evaluated with respect to feasibility. It appeared to be fairly feasible, provided sufficient opportunity for practice is given. Two series with inter-stimulus intervals of 4 and 3 seconds respectively were then evaluated with respect to validity and reliability in subjects of 48 to 74 years. Both Pasat series correlated well with two tests of attention: Digit Symbol (WAIS) and d2-test (r = 0.53-0.67), the relation with reaction decision speed being generally weak (r = 0.29-0.33) and weak to absent with a number of memory tests (r = -0.04-0.29). The Pasat performance shows a positive relationship with educational level and intelligence (inter-stimulus interval 4 seconds: r = 0.28 and 0.33 resp.; inter-stimulus interval 3 seconds: r = 0.40, 0.57 resp.). The stability of test performance over a period of about two months is moderate (r = 0.54, 0.61 resp.). In view of the excellent inter-observer reliability (r = 0.99) and the good parallel-test reliability (r = 0.79, 0.68 resp.), this might be explained by fluctuations in the capacity measured, rather than measurement error.(ABSTRACT TRUNCATED AT 250 WORDS)


Recognition and treatment of surgical wound infections.

1. Tissue traumatized by surgery heals in a three-phase sequential process: a defensive response to the injury, reconstruction of the site, and maturation (closing) of the wound. 2. Not all patients undergoing surgery are at equal risk for infection. The anatomic location of the surgery, the seeding of the surgical site with the patient's own normal flora, the OR environment and personnel, and the presence of a foreign body left in place after closure all contribute to the risk of infection. 3. The treatment of postoperative infection can be divided into the physical aspects of wound care and the appropriate use of antimicrobial agents.


The facts about methicillin-resistant Staphylococcus aureus.

1. Staphylococcus aureus is a gram-positive organism that can be cultured from the anterior nares of 30% to 40% of the general population. S aureus causes about 10% of all nosocomial infections, and is the leading cause of surgical wound infections. 2. Several factors can influence the recovery of MRSA from specimens, including mixed cultures in the person, a person who is an intermittent carrier, and a culture that is taken or transported incorrectly. 3. Two approaches can be used to reduce the risk of cross-transmission of organisms among patients and health-care workers: a generic infection precautions strategy for all patients, and identifying patients infected or colonized with MRSA and treating them differently than other patients.


Reducing occupational exposure to blood in the OR.

1. Many occupational exposures to blood in the operating room can be prevented. Some percutaneous injuries may not be preventable, but their frequency can be reduced by implementing engineering and work practice controls. Work practice controls and personal protective equipment can help eliminate mucocutaneous exposures to blood. 2. Identifying risk factors for intraoperative exposure is a vital step in presurgical and intraoperative assessment to plan infection prevention and control interventions. The decision to use risk reduction strategies should be based on probability and type of exposure anticipated rather than on the index of suspicion for bloodborne infection in the patient. 3. The responsibility for using safety and barrier precautions in the operating room remains that of the health-care worker. Not only the patient, but also the health-care worker need to be protected.


Feeling personal power.

Feelings of personal power are important for personal feelings of well-being. Although feelings of personal power relate to authority, either given by others or acquired with the job, personal power is largely a personal feeling that is created and can be developed. Careful assessment of position power, expertise power, and personal characteristics that add or detract from personal power can increase self-awareness and cause strong areas to be maximized and weak areas to be developed. With the development of feelings of personal power come feelings of confidence in a nursing role. Feelings of personal power also benefit the nursing profession because this enables the profession to grow in strength and pride.


Surgical wound infection rates: use caution when comparing.

1. Comparing surgical wound infection (SWI) rates without a complete understanding of and at least a partial control for those factors that can account for observed variations can be misleading. 2. Variations in SWI rates can be attributed to patient-related factors, type of operation, differences in case finding, differences in definition of SWI, and chance variation. 3. Use of a risk stratification prior to rate calculation controls for intrinsic (patient-related) and extrinsic (operation-related) risk for the purpose of comparison.


Perioperative antibiotic prophylaxis: the importance of timing.

1. Although prophylactic antibiotics have demonstrated efficacy in surgical procedures, they can fail because, generally, an inappropriate agent is used or the agent is inappropriately administered. 2. The timing of administration is important. Studies indicate that to reduce the risk of infection, high levels of antibiotic must be present in the bloodstream and tissues at the time of the incision. 3. Nurses play a central role in ensuring the proper timing of the administration of prophylactic antibiotics. Improvement in the timing of administration will reduce both morbidity and institutional costs.


The port: delivering intraperitoneal chemotherapy in ovarian cancer.

1. Ovarian cancer is rarely diagnosed in the early stages because there are no easily identifiable signs and symptoms. When recognizable signs and symptoms appear, they are commonly unimpressive, elusive, and vague. 2. A significant advantage of intraperitoneal administration of chemotherapy is that high concentrations of drugs can be maintained within the peritoneal cavity with less systemic toxicity than with intravenous administration of similar doses. 3. Surgically implanted ports allow for a completely closed system, eliminating the need for daily care and greatly reducing the potential for infection.


Intraoperative radiation therapy.

1. Local and regional recurrence of disease is a major problem in cancer management. Intraoperative radiation therapy (IORT) combines surgery with irradiation to treat any disease remaining after surgery and to decrease the local recurrence rates for certain cancers. 2. The development of an IORT treatment program is often undertaken by groups and institutions with expertise in multidisciplinary oncology, particularly surgical and radiation oncology. The program uses multiple resources, requiring cooperation and teamwork to achieve an efficient procedure with maximum patient outcome. 3. The process should be reviewed and modified each time it is performed. There is no "standard" way to use IORT, and every program will have variations that adapt to the circumstances existing in each specific facility.


Head and neck cancer resection and reconstruction: from past to present.

1. Head and neck tumors occur predominantly in men between 50 and 70 years of age who typically abuse tobacco or alcohol. These individuals often have poor oral hygiene and dentition as well as nutritional deficits, and achlorhydria, anemia, and iron and riboflavin deficits are common. 2. The tumor and treatment of head and neck cancer may cause many devastating effects, such as facial disfigurement, dysphagia, alterations in airway and communication, partial or total loss of taste and smell, xerostomia, pain, or fatigue. Treatment and rehabilitation may take months. 3. Although advances in technology and reconstructive surgery have not improved the overall survival rate, they preserve appearance, function, and, ultimately, the patient's quality of life.


American Cancer Society services for cancer patients.

1. As the incidence of cancer continues to rise among Americans, the number of new cancer patients increases along with the survival rates. It is becoming increasingly important for nurses to recognize and respond to the needs of those living with cancer. 2. Those faced with cancer fear death, disfigurement, financial ruin, and isolation from their friends and loved ones. Patients and families have tremendous needs for assistance but do not know where to turn. Nurses in any practice setting can help these patients access community resources. 3. The American Cancer Society is a national organization offering programs for patients and families in the areas of resources, information, and guidance; education and support programs; and direct services.


Breast cancer surgery: understanding the story.

1. Research has shown that mastectomy, with or without reconstruction, is no more effective in the long run than breast conservation and irradiation. Therefore, the important factor seems to be choice. 2. A Halsted radical mastectomy involves the removal of the whole breast along with the pectoralis major and minor muscles and a complete axillary dissection. A modified radical mastectomy involves removal of the whole breast and most or all of the axillary lymph nodes, but preserves the pectoralis major muscle. 3. Breast preserving strategies remove the malignant cells and minimal surrounding tissue. These segmental resections include lumpectomy, quadranectomy, and wedge resection along with axillary node dissection.


A DNA hybridization assay for use in drug sensitivity tests in vitro for Plasmodium falciparum under field conditions.

A deoxyribonucleic acid (DNA) hybridization technique was applied to in vitro drug sensitivity testing of P. falciparum using a synthetic 21-mer oligonucleotide coupled to alkaline phosphatase (PFR1-AP) to monitor development of parasite stages in culture. The density of the coloured spot clearly distinguished schizonts from ring forms. This assay system was applied in the field on Hainan Island, China. Blood samples obtained from patients were cultivated in the presence of antimalarial drugs and the minimum drug concentration required to inhibit development of parasites was determined by the DNA hybridization assay and by microscopical observation of Giemsa-stained blood smears. The 2 methods yielded identical results, indicating that the DNA hybridization assay can be used for in vitro drug sensitivity testing under field conditions.


Chloroquine sensitivity of Plasmodium falciparum in vivo in a savanna town in Cameroon.

Chloroquine-resistant Plasmodium falciparum has been reported in the Sahel and forest regions of Cameroon since 1985. In vivo response to chloroquine treatment (25 mg/kg) was assessed in 19 patients with malaria in the savanna North-West province. 58% of the cases showed RII resistance to chloroquine. RIII resistance was suspected in one patient. Only 35% of cases showed complete parasite clearance by day 5 of treatment. Chloroquine reduced parasite counts by at least 87% in all patients. Chloroquine resistance now seems to be well established and widespread in Cameroon. Its rapid spread and the prevalence of resistance suggest the existence of sustained drug pressure resulting in rapid selection of less sensitive strains. Unfortunately, similar pressure is also being exerted with quinine.


The role of shops in the treatment and prevention of childhood malaria on the coast of Kenya.

A community survey of 388 mothers in a rural and peri-urban population surrounding a district hospital on the coast of Kenya revealed that the preferred choice of treatment for childhood febrile illnesses was with proprietary drugs bought over the counter at shops and kiosks (72% of interviews). 67% of the mothers who reported using shops claimed they would buy chloroquine-based drugs. Preventative measures such as mosquito nets were uncommon (6.2%), but the use of commercial pyrethrum mosquito coils was reported more frequently (46.4%). Separate investigations of treatment given to 394 children before presentation at hospital with severe and mild malaria was consistent with the reports in the community of high usage of shop-bought anti-malarials and anti-pyretics. The involvement of the private sector in peripheral health care delivery for malaria is discussed.


Plasmodium falciparum: sensitivity to chloroquine in vivo in three ecological zones in Ghana.

4690 children aged 6-15 years in 5 urban and 4 rural communities in 3 ecological zones in Ghana were screened from June 1988 to December 1990 to provide suitable candidates for the World Health Organization standard in vivo test for susceptibility of Plasmodium falciparum to chloroquine. 1880 (40.1%) had parasitaemia, mostly (83.7-98.6%) due to P. falciparum infection. Of the 626 in vivo tests performed, 570 (91.1%) showed sensitivity to chloroquine and 56 (8.9%) responses were classified as resistant to chloroquine at RI (5.1%) and RII (3.8%). The resistance responses were commonest (17.1-22.7%) in the coastal zone, followed by the savanna zone (8.6-10.0%), and lowest in the forest zone (3.1-6.3%). The RII responses occurred mainly in communities in the coastal zone. There was no RIII resistance in any zone. The pattern of RI (early) and RII responses of P. falciparum to chloroquine in this study suggested an increase in sensitivity, or a reduction in resistance, of P. falciparum to chloroquine from the coast to the forest and northern savanna zones, and from the urban to the rural communities in each zone in Ghana.


Lack of effect of desipramine on the response to chloroquine of patients with chloroquine-resistant falciparum malaria.

The potential of desipramine to improve the efficacy of chloroquine against chloroquine-resistant Plasmodium falciparum in vivo in man was investigated. Fifty-three malaria patients were selected according to the criteria for the standard World Health Organization (WHO) in vivo test and were randomly divided in 2 groups. One group (n = 27) was given standard therapeutic doses of chloroquine (25 mg/kg body weight of base) and the other (n = 26) was given standard doses of chloroquine, as above, in combination with desipramine (1.3-2.8 mg/kg body weight) daily for 3 consecutive days. Standard WHO in vitro micro-tests were performed in parallel with the tests in vivo to provide chloroquine sensitivity patterns of the P. falciparum parasites. The results in vitro from both groups did not differ with regard to chloroquine sensitivity and the means of the pre-treatment parasite densities were similar. There was no apparent difference in parasite clearance in vivo between the 2 groups. This study provided no evidence for enhanced chloroquine efficacy in vivo through the use of desipramine in doses corresponding to the usual therapeutic range.


Haemoglobin-E in the presence of oxidative substances from fava bean may be protective against Plasmodium falciparum malaria.

A case-control study was carried out at a community hospital in eastern Thailand in order to study the association between haemoglobin E and Plasmodium falciparum malaria; 271 P. falciparum cases and 271 controls were enrolled. After adjusting for age, sex, time since last malaria attack, history of mosquito net use, and history of fava bean consumption in the previous month, neither heterozygous nor homozygous haemoglobin E provided significant protection against P. falciparum infection, with odds ratios (OR) = 0.91 (95% confidence limits = 0.61, 1.36) and 0.78 (0.34, 1.82) respectively when compared to persons with haemoglobin A who were not consumers of fava beans. However, haemoglobin E carriers who ate fava beans were significantly protected against P. falciparum malaria with OR = 0.26 (0.09, 0.76) and OR = 0.001 (0.00, 1120.59) for subjects with heterozygous and homozygous haemoglobin E, respectively. The study suggests a possible synergistic protective effect of haemoglobin E on the risk of P. falciparum malaria in subjects who have consumed fava beans.


Leishmanin reaction in the human population of a highly endemic focus of canine leishmaniasis in Alpes-Maritimes, France.

The reactivity of the human population was studied in the village of l'Abadie, a suburban focus of canine leishmaniasis (17% of dogs seropositive in 1985); 237 subjects were tested in 1989. The total positive rate was 30%. A higher proportion of positive skin tests was obtained in the 61-70 years age group (62%) than in the younger groups. The proportion of positive tests also increased with the duration of living in this locality (22% for less than 5 years; 66% for more than 21 years). These data confirm the continuing occurrence of transmission of leishmaniasis to human beings in this focus.


High-dose nifurtimox for arseno-resistant Trypanosoma brucei gambiense sleeping sickness: an open trial in central Zaire.

Thirty patients with arseno-resistant Trypanosoma brucei gambiense sleeping sickness were treated with high-dose nifurtimox (30 mg/kg/d for 30 d). During treatment, the cerebrospinal fluid (CSF) white blood cell (WBC) count decreased in all patients except one (mean CSF WBC count before nifurtimox: 117/mm3; after nifurtimox: 25/mm3), and trypanosomes disappeared from the CSF of all 9 patients in whom parasites had been demonstrated before nifurtimox. Among 25 patients seen at least once after treatment, 9 (36%) have relapsed so far. High-dose nifurtimox was significantly toxic: one patient died during treatment and 8 others developed adverse neurological effects. High-dose nifurtimox seems more effective than the previously used regimen (15 mg/kg/d for 60 d), but at the expense of significant toxicity.


Is leishmaniasis ever cured?

The persistence of parasites in mice cured of Leishmania mexicana infection was investigated by using immunosuppressive drugs and checking for the reappearance of lesions. BALB/c (susceptible) and C57BL/6 (partially resistant) mice infected with 10(4) amastigotes were treated with either thermotherapy or meglumine antimonate and subsequently immunosuppressed with either cyclophosphamide or hydrocortisone. Immunosuppression by either method caused lesions to reappear in both strains of mice regardless of the treatment used to produce clinical cure. In both strains of mice the proportion of animals developing lesions after immunosuppression was greater in the mice cured by the drug. The relevance of these findings to human therapy is discussed.


Relative efficacy of melarsen oxide compared with mel Cy (Cymelarsan) when used in combination with difluoromethylornithine in the treatment of trypanosomiasis of the central nervous system.

A comparison was made between the efficacy of mel Cy (Cymelarsan) and melarsen oxide to cure central nervous system trypanosomiasis in a chronic Trypanosoma brucei mouse model. Combination treatment with difluoromethylornithine and arsenical was used and it was found that there was only a marginal advantage in using the water-soluble mel Cy in terms of the numbers of mice cured.


Detection of high titres of Toxoplasma gondii antibodies in sera of patients with leprosy in Pakistan.

Untreated and treated leprosy patients and their household contacts were screened for antibody to Toxoplasma gondii using antigen-coated latex particles. A significantly high level of seroprevalence (29.6%) was observed in the untreated leprosy patients compared to endemic controls (P < 0.01) with a mean reciprocal antibody titre of 20,007 +/- 3580 (n = 98) in seropositive patients. In treated patients seroprevalence dropped to 13.5%. Seroprevalence in a group of household contacts of leprosy patients was similar to that of control subjects from an endemic area but not exposed to leprosy (7.8% and 6.1% respectively), indicating that the increased seroprevalence in leprosy patients was not merely due to increased exposure related to socioeconomic factors. Antigenic cross-reactivity between T. gondii and Mycobacterium leprae antigens was ruled out by cross inhibition experiments carried out with soluble antigens from each of the organisms. We believe these antibodies may be induced by an increase in T. gondii load in leprosy due to a transient reactivation of latent T. gondii infections, as the antibodies in these leprosy patients were not associated with any sign of eye or lymphatic pathology related to toxoplasmosis.


Estimation of the number of cases of schistosomiasis in a country: the example of Cameroon.

An estimate of the number of schistosomiasis infections in Cameroon was based on a statistically representative national prevalence survey carried out in the entire country. The number of cases of infection by Schistosoma haematobium was estimated to be 393,900, and 419,600 for S. mansoni, a total of 813,500. Taking into account the dual infections the total number of cases was 719,100 (95% confidence interval: 392 900-1 027,800). A current World Health Organization estimate extrapolating from the results of limited epidemiological surveys showed 2,239 591 cases for Cameroon, an estimate 3.1 times higher than the more accurate estimate based on the national survey. Schistosomiasis being a focal disease, prevalences observed in limited foci are not representative of regional prevalences. Prevalence survey data in the literature are biased toward reporting only positive results. Therefore extrapolations made on limited surveys may lead to an overestimation of the number of cases of schistosomiasis.


Low seroprevalence of Toxoplasma gondii antibodies in a Tanzanian village.

The prevalence of antibodies against Toxoplasma gondii was studied in the population of Nyamisati village in Tanzania using the direct agglutination test, indirect immunofluorescence test, and immunosorbent agglutination test. All positive sera were positive by both direct agglutination and indirect immunofluorescence tests and were confirmed by the dye test. The seropositivity was confirmed by immunoblotting showing a distinct 32 kDa band in all the seropositive samples. The seropositivity rate was 4% (19/450) among the subjects of Nyamisati origin and 47% (15/32) among immigrants from other areas of Tanzania. Most of the infections appeared to have occurred between 5 and 15 years of age. The generally low transmission in this mainly Muslim village appeared to be related to sparse consumption of contaminated food and low prevalence of oocysts due to scarcity of felines.


Nutritional status of children with schistosomiasis mansoni in two different areas of Machakos District, Kenya.

A possible association between nutritional status and Schistosoma mansoni infection or morbidity was investigated by comparing anthropometric indices among 362 children from 3 primary schools in Machakos District, Kenya. Matithini was a prosperous school in an area (Kangundo) of moderate intensity of schistosome infection but low associated morbidity. A second area (Kambu) showed more severe schistosome-associated morbidity: in this area, Kitengei school was prosperous and with high intensities of schistosome infection, while Misuuni school was less prosperous and with low intensities of infection. Nutritional status was assessed by measurement and appropriate standardization of height, weight and skinfold thickness and by questionnaires concerning diet. Children in Kangundo were better nourished than those in Kambu. Within Kambu, children from Misuuni showed low mean skinfold thickness and low mean weight-for-height ('wasting'): this was associated with a lack of dietary variety and of intake of animal products. In contrast, those from Kitengei showed low mean height-for-age ('stunting'). The relationship between intensity of schistosome infection and nutritional indices, although significant, was complex and not readily interpretable. However, intensity of infection was also correlated with hepatomegaly, which was more clearly related to nutritional status. Depending on the school, children with hepatomegaly were significantly more stunted and/or wasted than those without, and had less variety in their diet. Possible reasons for the observed associations are discussed and, of various possibilities, the hypothesis is suggested that schistosome-associated morbidity leads to a subsequent nutritional defect. This hypothesis can now be tested by appropriate intervention studies.


A community trial of ivermectin for onchocerciasis in Sierra Leone: clinical and parasitological responses to four doses given at six-monthly intervals.

Clinical and parasitological responses were studied in villagers receiving all 4 doses of treatment, at 6-monthly intervals, in a placebo-controlled community trial of ivermectin for onchocerciasis in Sierra Leone. Skin microfilarial loads were markedly lowered by ivermectin throughout and there were reductions in the severity, but not the prevalence, of skin lesions. Markers of general health and the prevalences of itching, Onchocerca nodules and visual loss were not significantly reduced during the study period. Despite our inability to demonstrate obvious clinical benefit, treatment with ivermectin was well accepted throughout the study. Simple clinical measures for evaluating the short to medium term impact of the mass distribution of ivermectin on populations with onchocerciasis need further development.


Adverse events following mass ivermectin therapy for onchocerciasis.

The Achi community of south-east Nigeria was given mass ivermectin therapy to control endemic onchocerciasis. 7556 subjects (75.6% of those eligible) were dosed. 992 patients (13.1%) complained of adverse effects, mostly within one week of dosing. Adverse events were mainly of the Mazzotti type. Exacerbation of pruritus (71.2%), oedema (47.4%), headache (46.4%), and worsening of rash (24.4%) were the most common. In 962 subjects (97%), adverse events were mild and did not prevent work. Two patients suffered severe sustained postural hypotension. The incidence of adverse events was greater in villages with a high load of microfilarial infection.


Ivermectin does not reduce the burden of itching in an onchocerciasis endemic community.

Degrees of itching were estimated before and for 6 months after a fourth dose of ivermectin or placebo was given to 97 subjects in Sierra Leone. There was no reduction in itching attributable to ivermectin at any stage, but there were non-significant increases in the prevalence, severity and localization of itching within the first 2 months after ivermectin compared to placebo. We also found that cell-mediated immune responses to Onchocerca volvulus were significantly increased 4 weeks after a single dose of ivermectin compared to before treatment. A temporary reversal of the state of immunosuppression in people with onchocerciasis may counterbalance the reduction in skin microfilarial loads following ivermectin, with no consequent reduction in itching. The lack of effect of ivermectin on itching, a major symptom of onchocerciasis, while disappointing, need not detract from the success of mass distribution programmes.


Long-term suppression of microfilaraemia following ivermectin treatment.

Lymphatic filariasis has been difficult to control until recently because of the lack of a suitable drug for treatment. Ivermectin has proven safe and effective at reducing levels of circulating microfilariae. However, the apparent need to administer the drug every 6 to 9 months to keep microfilaraemia levels sufficiently suppressed to reduce transmission has been a major drawback to using ivermectin in community-based intervention programmes. In a study conducted in Haiti, we have found that high doses of ivermectin suppress microfilaraemia levels for 2 years. Our findings suggest that a single dose of ivermectin can reduce transmission of lymphatic filariasis for extended periods of time, thus eliminating the need for costly biannual treatment.


Serological response to tetanus toxoid: a field study in Pondicherry, India.

To study the serological response to various doses of tetanus toxoid given to pregnant women, 320 samples of blood obtained from 173 pregnant women were analysed using the indirect haemagglutination technique. Two doses of toxoid were necessary to achieve protective titres in women who were previously unimmunized. The antibody levels appeared to persist for up to 4 years. During a subsequent pregnancy, a single booster dose of toxoid was sufficient to raise the titres adequately for protection. These findings are in accordance with the immunization programme followed for prophylaxis against tetanus among pregnant women.


Sero-epidemiological studies of respiratory syncytial and adenoviruses in children in Ibadan, Nigeria, 1985-1988.

Retrospective and prospective serological surveys to determine the prevalence of respiratory syncytial virus (RSV) and adenovirus (ADV) infections in children with respiratory diseases were carried out from 1985 to 1988 at the University College Hospital, Ibadan, Nigeria. 306 sera from subjects between 3 months and 12 years old were assayed by complement fixation test for antibodies to both viruses. Second samples were available from 42 of the subjects for antibody conversion testing. The rate varied with age, period of the year and virus. Overall prevalences of 23.5% and 18.3% were obtained for RSV and ADV respectively. 2.6% of the subjects had antibodies to both viruses. Among 42 paired samples tested, 61.9% and 33.3% showed positive antibody conversion to RSV and ADV respectively. Although there was evidence of active circulation of both viruses throughout the year, infection with RSV was higher from September to January, while ADV infection was significantly higher during February and March. Antibody prevalence to both viruses increased with age up to a peak of 39.1% for RSV in children 5-6 years old and 32% for ADV in children 3-4 years old. None of the subjects aged 10 years and above was positive for both viruses. Both RSV and ADV are important agents of acute respiratory infection in children in Nigeria.


Detection of circulating antigens in human trichinellosis.

A 'sandwich' enzyme-linked immunosorbent assay was established to detect circulating antigens of Trichinella spiralis in human sera, its sensitivity and specificity was evaluated using 4 antigens (Trichinella spiralis, Trichuris trichiura, Dirofilaria immitis and Ascaris suum), and it was found to be sensitive and specific for T. spiralis antigen. Samples of 347 individuals with suspected trichinellosis, who had eaten incompletely cooked bear meat containing larvae of T. spiralis, were examined. Among individuals showing clinical symptoms, circulating antigens were detected in 29.9%, and the prevalence of antibodies was 18.9%. Among individuals lacking clinical symptoms, antigens were detected in 21.4% and antibodies in 5.0%. It was concluded that detection of circulating antigens was more useful for making diagnoses than measurement of specific antibodies.