'Sports anemia'--a real or apparent phenomenon in endurance-trained athletes?

In order to critically define the apparently widespread condition 'sports anemia', the red cell indices and iron status of male distance runners and triathletes, and female distance runners and ballet dancers were compared to non-exercising controls of both sexes. The mean hemoglobin (Hb) levels of all groups were within the normal ranges and there was no difference between the athletic and control groups of each sex. The mean serum ferritin (SF) concentration of the male distance runners (79.8 micrograms/l) was significantly lower than that of the triathletes (123.5 micrograms/l) and controls (138.3 micrograms/l). Iron deficiency (SF less than 12 micrograms/l, % saturation less than 18%) was evident in 3.3% and 5% of the male and female runners respectively, and 3.3% of the ballet dancers. Iron deficiency anemia (abnormal red cell indices and iron status) occurred in only 1.7% and 3.3% of the male and female distance runners respectively, and 3.3% of the dancers. However, 7 (11.7%) each of the male and female distance runners and 6 (20.0%) of the ballet dancers recorded hemoglobin values lower than the normal range of 140 g/l and 120 g/l for males and females respectively. This anomaly can be explained by a significantly expanded plasma volume in endurance-trained individuals, causing a 'pseudoanemia'. We conclude therefore that athletes are at no greater risk for developing a frank anemia than the non-exercising population, and that the term 'sports anemia' is misleading, as it does not describe a specific clinical entity.


Serum keratan sulfate levels in marathon runners.

The effect of strenuous joint loading on the metabolism of articular cartilage in man is not known. The development of a non-invasive immunoassay for the assessment of the catabolism of cartilage aggrecan has enabled us to quantify keratan sulfate (KS), a component of aggrecan, in the serum of fifteen male marathon runners. Serum KS was measured by an ELISA before and immediately after a marathon (42 km), as well as 48 hours after the completion of the race. The mean level at rest was similar to those previously reported for another population of age-matched males. There was no statistically significant difference in the serum level of KS at the three different readings. Further, there was no correlation between age, height, weight and performance time, and the serum level of KS at any of the three different times. We conclude that marathon running by carefully trained runners causes neither a transient nor a sustained increase in proteoglycan catabolism in articular cartilage.


Hand injuries in volleyball.

We studied the long-term sequelae of hand injuries as a result of playing volleyball. In a retrospective study, 226 patients with injuries of the hand who were seen over a 5-year period at our Trauma Department, were investigated. Females accounted for 66% of all injuries. The mean age was 26 years, with a peak in the age group of 15 to 29 years. Sprains and strains were observed most frequently (39%), followed by fractures (25%) and contusions (16%). The fingers were involved in 44% of the cases. Most injuries of the hand occurred in recreational players. Recreational players had more left-sided injuries, whereas competition players had more right-sided injuries (P less than 0.005), suggesting that lack of skill is an important determinant. Left-handedness was associated with an increased risk of hand injury in recreational players. One third of the volleyball players did not go to work or school for a median of 4 weeks as a result of the injury. In a survey after a mean period of 5 years, a high percentage of patients had complaints: 28% cited stiff and crooked fingers with limitations and tenderness in the movements as main inconveniences. We consider this incidence disturbingly high, regarding the seemingly innocent nature of these injuries.


A simple method for determining critical speed as swimming fatigue threshold in competitive swimming.

The purpose of this investigation was to determine whether the concept of the critical power could be applied to competitive swimming by using critical swimming speed (CS) as determined both in the swimming flume (CS-flume) and in the normal swimming pool (CS-pool) and whether CS could be utilized as a practical index for assessing a swimmer's endurance performance. CS defined as the swimming speed which could be theoretically maintained continuously without exhaustion was expressed as the slope of a regression line between swimming distance (D) and its duration (T) obtained at various swimming speeds. Eight highly trained swimmers were instructed to swim until onset of fatigue at four predetermined swimming speed levels in the swimming flume and at maximal effort over four different swimming distances in the swimming pool. In the results of CS-flume and CS-pool, the regression relations between D and T were expressed in the general form, D = a+b x T, with r2 being higher than 0.998 (p less than 0.01), respectively. These results both from the flume and the pool indicated extremely good linearity. Furthermore, maximal oxygen uptake (VO2max) during the incremental exercise test, swimming speed corresponding 4 mM of blood lactate concentration (V-OBLA) and mean velocity in the 400 m freestyle (V-400) were measured on each subject.(ABSTRACT TRUNCATED AT 250 WORDS)


Performance measures, blood lactate and plasma ammonia as indicators of overwork in elite junior weightlifters.

The effects of short-term overwork on performance measures, blood lactate, and plasma ammonia concentrations were examined in 28 elite junior weightlifters who participated in a 2 wk high volume resistance training camp. Performance testing (maximum effort vertical jump test and snatch lift) and blood chemistry analyses (ammonia and lactate) were conducted before (T1) and after (T2) 7 d of high volume training (2-3 workouts/d). Blood samples were collected from an antecubital vein at rest, preexercise, 5 min postexercise, and 15 min postexercise at T1 and T2. Results indicated a significant decrease from T1 to T2 in the maximum effort vertical jump test while the snatch lift test yielded no difference across time. Blood lactate and ammonia concentrations were significantly lower at 5 min postexercise at T2 while resting ammonia concentrations were significantly elevated at T2 compared to corresponding measures at T1. These data suggest possible early symptoms of overwork at T2 (decrease in performance of the maximum effort vertical jump test and the elevated resting ammonia concentrations); however, lower 5 min postexercise concentrations of lactate and ammonia at T2 indicated a positive adaptation to the 1 wk high volume resistance training period.


The effect of training intensity on ratings of perceived exertion.

We examined the effects of intensity of training on ratings of perceived exertion (RPE) at the lactate threshold (LT), fixed blood lactate concentrations (FBLC) of 2.0, 2.5 and 4.0 mM and peak in 25 untrained eumenorrheic women (mean +/- SD: age = 30.9 +/- 4.1 yrs; height = 165.7 +/- 5.9 cm; weight = 65.5 +/- 7.6 kg) who completed one year of run training. Subjects were recruited as sedentary controls or were randomly assigned to one of two training groups: 1) at the lactate threshold (at LT) or 2) above the lactate threshold (greater than LT). The at LT group trained at velocity LT and the greater than LT group trained at the velocity midway between velocity LT and peak velocity. Training subjects were reevaluated every fourth menstrual cycle and training intensity was adjusted. The control group was reassessed at menstrual cycle 12. Before training no among group differences were observed for VO2 or velocity at LT, FBLC and peak. Both training groups increased VO2 at LT, FBLC and peak as a result of training (p less than 0.05), with the greater than LT group exhibiting greater improvement than the at LT group (VO2 at LT, FBLC of 2.0, 2.5 and 4.0 mM and peak increased by 6.4, 5.3, 5.1, 4.0 and 4.7 ml/kg.min-1 for at LT and by 10.4, 9.2, 8.6, 5.1 and 5.9 ml/kg.min-1 for greater than LT; p less than 0.05). Similar findings were observed for the velocity associated with these lactate concentrations. No pre/post differences were observed in VO2 or velocity for the control group.(ABSTRACT TRUNCATED AT 250 WORDS)


Cardiac responses of young women to conditioning for a 10 kilometer race.

Seven previously sedentary women (mean age, 19 yrs) participated in an 11-week running program (4-5 sessions/week) in preparation for a 10 km race. Training intensity was 80-85% of maximum heart rate reserve. Exercise duration began at 20 minutes/session and was lengthened 5 minutes/session every 2 weeks. A control group consisting of 4 women was also evaluated. Maximal oxygen uptake (VO2max, ml/kg/min) increased 11% in the trained group and decreased 6% in the control group during the study (p less than 0.05). Oxygen uptake, cardiac output (Q), and stroke volume (SV) increased significantly (p less than 0.05) in the trained group during each of 3 levels of steady state cycle ergometer exercise (heart rate targets: 115, 135 and 155 beats/min, respectively). Arteriovenous oxygen difference (a-V02 diff) was not increased significantly after training. Resting left ventricular dimensions and performance evaluated by echocardiography also did not change significantly after training. It was concluded that short-term conditioning in this population results in an increased exercise Q without concomitant increases in left ventricular dimensions or arteriovenous oxygen difference.


Characterization of the heart rate response during biathlon.

Continuous heart rate recordings were obtained on elite American bi-athletes during competitions to provide a better understanding of the physiological demands of biathlon and the strategies used in approaching the shooting range. The findings demonstrate that the average age heart rate during skiing was approximately 90% of maximum heart rate. Heart rates decreased 10-12 bpm over a time period of approximately 50-60 sec during the approach to the firing line. At arrival to the firing line, heart rates were similar for prone and standing shooting averaging 85-87% of maximum heart rate. Mean minimum heart rates while at the firing line dropped to 61-73% of maximum heart rate and averaged approximately 20 bpm lower for prone shooting. The lower minimum heart rates during prone shooting were accounted for by the bi-athletes spending a longer time at the firing line and having a more rapid decrease in heart rate while in the prone position.


The influence of the fullness of milk in the breasts on the concentration of lactic acid in postexercise breast milk.

The purpose of this study was to observe the influence of the fullness of breast milk in the breasts prior to exercise on the concentration of lactic acid in breast milk following exercise. Twenty-three lactating women were randomly assigned to Group E (n = 11), which nursed and/or collected as much of the breast milk as possible prior to maximal exercise, and Group F (n = 12), which did not nurse or collect milk at least two hours prior to maximal exercise. Milk was collected at rest preexercise and 10, 30, 60 and 90 minutes postexercise and was analyzed for concentrations of lactic acid. ANOVA demonstrated 1) a significant increase in lactic acid in the milk at all postexercise collections for both groups and 2) a significant group vs postexercise time interaction for lactic acid concentration in milk. These differences represented differences in 1) time to peak lactic acid concentrations in milk (Group F = 10 min; Group E = 30 min) and 2) time for postexercise decreases in lactic acid concentrations in milk. Thus, the state of fullness of milk in the breasts is a factor which affects the concentration of lactic acid in breast milk following maximal exercise.


Rehydration after exercise with common beverages and water.

This study assessed the effectiveness of two common rehydration beverages (a caffeinated diet cola (DC) and a 6% carbohydrate-electrolyte (CE) solution) compared with water (W) for whole body rehydration, gastric emptying and blood volume (BV) restoration during a 2 h rehydration period following exercise-induced dehydration. Subjects (mean VO2max = 4.2 +/- 0.6 l.min-1.min-1; n = 19) exercised at 60-80% VO2max in the heat (32 degrees C; 40% rh) until approximately 2.5% (1.95 +/- 0.12 kg) of their body weight (BW) was lost. After exercise, the subjects sat for 2 h in a thermoneutral environment (21 degrees C; 60% rh) and drank a volume of DC, W and CE equal to the fluid lost. Fluids were consumed in two boluses averaging 1,046 +/- 198 and 912 +/- 186 ml at 0 and 45 min of the 2 h rehydration period, respectively. At the end of the rehydration period, no fluid remained in the stomach during any of the trials as indicated by epigastric impedance. However, in all the trials the subjects were somewhat hypohydrated (range 0.6-0.9 kg BW below euhydrated BW; p less than 0.05) after the 2 h rehydration period since additional water and BW were lost as a result of urine formation, respiration, sweat and metabolism. The percentage of body weight loss that was regained (used as an index of % rehydration) during DC (54 +/- 5%) was significantly lower than that of W and CE (64 +/- 5% and 69 +/- 5%, respectively; p less than 0.05; n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)


Load and velocity of contraction influence gross and delta mechanical efficiency.

The effects of three different cadences and five different work rates on Gross (GE) and Delta Efficiency (DE) during cycle ergometry were studied. Fifteen well-trained cyclists exercised for 30 minutes at 60, 80, or 100 RPM on three different occasions. On each occasion, the load was increased every five minutes and corresponded to approximately 50, 60, 70, 80 and 90% of VO2max. During the last three minutes of each stage, steady-state energy expenditure was calculated while work rate was recorded. In addition, the oxygen cost of unloaded cycling (CUC) was also measured. GE was calculated as the ratio of work rate to the rate of energy expenditure, whereas DE was calculated as the reciprocal of the slope of this relationship at work rates between 50 and 90% of VO2max. The CUC corresponded to 0.66 +/- 0.03 l/min, 0.77 +/- 0.04 l/min and 1.04 +/- 0.04 l/min at 60 RPM, 80 RPM and 100 RPM, respectively (p less than 0.01 for all comparisons). GE was similar at all cadences when cycling at 80 and 90% VO2max. DE increased with increasing rpm and corresponded to 20.6 +/- 0.4%, 21.8 +/- 0.6%, and 23.8 +/- 0.4% at 60 RPM, 80 RPM and 100 RPM, respectively (p less than 0.01 for all comparisons). Therefore, when trained cyclists exercise intensely (80-90% VO2max), GE is similar at cadences of 60, 80 and 100 RPM, despite the significant increase in the CUC. Thus, it is possible that delta efficiency increases with increasing cadence.


Exercise training-induced alterations in skeletal muscle oxidative and antioxidant enzyme activity in senescent rats.

Limited data exist concerning exercise training-induced alterations in skeletal muscle oxidative and antioxidant enzyme activity in senescent animals. Therefore, the purpose of this study was twofold: 1) to examine the exercise training-induced changes in oxidative and antioxidant enzyme activity in skeletal muscle of old rats; and 2) to critically analyze the relationship between oxidative and antioxidant enzyme activities in skeletal muscle in both trained and untrained senescent rats. Female Fischer-344 rats (approximately 24-mo-old) were divided into 1) exercised trained (ET; n = 10) and 2) sedentary (S; n = 6) groups. The ET rats performed a 10-week training program of treadmill exercise (approximately 60 min, 5 days/wk). Training significantly (p less than 0.05) improved VO2max (delta 22.8%) in the ET rats above their age-matched controls. Further, the ET group had significantly elevated (p less than 0.05) activities of succinate dehydrogenase (SDH) in the soleus and red gastrocnemius (RG) muscles as well as greater (p less than 0.05) 3-hydroxyacyl-CoA dehydrogenase (HADH) activity in the RG when compared to the S group. However, training did not alter (p greater than 0.05) HADH activity within the white gastrocnemius (WG) or soleus muscles. Activity of the antioxidant enzyme, glutathione peroxidase (GPX) was higher (p less than 0.05) in the soleus and RG in ET rats when compared to the S rats; in contrast, training did not alter (p less than 0.05) GPX activity in the WG. Finally, the correlation coefficients between SDH and GPX activities (combined ET and S groups) for the RG, WG, and soleus muscles were r = .73, .17 and .36, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


NMR spectroscopy study of heart phospholipids. An exercise and anabolic steroids effect.

Because 31P NMR spectral analysis of phospholipid (PL) is an accurate and rapid technique for resolving the quantity of PL resonances and involving minimum chemical manipulations that may affect the integrity of the tissue (24-26), we studied the effect of anabolic steroid injection, exercise training, or a combination of both treatments on whole heart phospholipids using 31P NMR spectral analysis. Male Sprague-Dawley rats were randomly assigned to 4 groups of 11 each: sedentary control (C), steroid-treated (ST), exercise-trained (E), and exercise plus steroid-treated (ES). The ST and ES rats were administered nandrolone decanoate by i.m. injection every 7-9 d during the 10 wk study, while the C and E rats were injected with glycerol. The exercise rats ran on a treadmill, wearing a collar weight for 50 min/day, 5 days/wk. There was a significant difference in body wt among the four groups at the conclusion of the study; however, no significant differences in heart wt or in the ratio of heart wt:body wt were observed among the four groups. Myocardial phospholipid profiles of the exercise-trained rats were significantly (p less than 0.05) different from those of the untrained rats. The changes were enhanced somewhat by the steroid treatment. The profiles differed in the relative amounts of four of the nine myocardial phospholipids detected: phosphatidylcholine, phosphatidylethanolamine (PE), PE plasmalogen, and phosphatidylserine. We conclude that the observed changes in whole heart phospholipid compositions are due to experimental treatment specifically from exhaustive exercise and not from anabolic steroids or cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)


The influence of diabetes mellitus on cardiovascular function in children and adolescents.

Early manifestations of non-atherosclerotic cardiomyopathy, a recognized complication of diabetes in adults, have been suggested to contribute to depressed levels of aerobic fitness described in children and adolescents with this disease. This study measured components of aerobic fitness and cardiovascular function during maximal cycle ergometer exercise in 11 insulin-dependent diabetic boys aged 10.2-16.5 years. Mean duration of diabetes was 4.5 years. Eleven non-diabetic subjects matched for age, body size, and regular physical activity served as controls. No differences in maximal oxygen uptake or heart rate were observed between the two groups, nor were any significant differences recorded in submaximal stroke volume, cardiac output, heart rate, and pressure-rate product. This study failed to reveal any evidence of functional myocardial disease in children and young adolescents with diabetes, suggesting that manifestations of diabetic cardiomyopathy should not be expected during the pediatric years. Moreover, these findings indicating normal cardiovascular function in young diabetic subjects imply that regular levels of habitual physical activity are more likely to affect aerobic fitness in these patients rather than influences of the diabetic state itself.


Altered cellular distribution of hexokinase in skeletal muscle after exercise.

The purpose of this study was to determine the effects of a single period of swim exercise to exhaustion on the cellular distribution of hexokinase in rat skeletal muscle. The gastrocnemius muscle from male rats exercised (n = 16) to exhaustion or allowed to remain inactive (n = 14) was analyzed for hexokinase activity (HK) in the whole muscle homogenate and the mitochondrial-rich fraction. Although exercise produced a slight, non-significant, increase in HK activity in the whole muscle homogenate (p less than 0.09), HK activity in the mitochondrial-rich fraction was significantly increased in the exercised muscle (p less than 0.02). This shift in the cellular distribution of HK is towards the more active mitochondrial bound form and indicates an enhanced regulation of HK activity during physical exercise.


Antioxidant status and cancer mortality in China.

Sex-specific mortality rates for selected cancer sites (including oesophagus, stomach, liver, lung, colorectum, breast and cervix) and a variety of biochemical indicators of antioxidant status, enzyme activity and oxidative stress (including plasma levels of beta-carotene, alpha-tocopherol, ascorbic acid, selenium, glutathione peroxidase, catalase, superoxide dismutase, iron, copper, zinc, total cholesterol and lipid peroxide) were examined in an ecological study of 65 mostly rural counties in the People's Republic of China. The wide range of both mortality rates and biochemical values and the measurement of a comprehensive set of biochemical indicators permitted both simple correlational and multivariate analyses of the joint and relative effects of each factor on site-specific cancer mortality. Plasma levels of dietary antioxidants were consistently negatively correlated with cancer mortality rates. Ascorbic acid was most strongly negatively associated with most cancers and selenium with oesophageal and stomach cancers. beta-carotene was found to have a protective effect independent of retinol, particularly for stomach cancer.


Reduced risk of hip fracture in women with endometrial cancer.

The effect of excessive endogenous oestrogens on the risk of hip fracture was investigated in a population-based cohort of 2111 women with endometrial carcinoma who were followed up from age 50 years regarding the occurrence of a first hip fracture. Overall, 77 cases of hip fracture were observed, as against 120.8 expected, which meant a significantly reduced relative risk, standardized incidence ratio (SIR) = 0.6, 95% confidence interval (CI): 0.5-0.8. This possible protective effect was significant for cervical fractures, SIR = 0.6 (95% CI: 0.4-0.8), but not for trochanteric, SIR = 0.8 (95% CI: 0.5-1.1). Age at endometrial cancer diagnosis was not a determinant of the risk of hip fracture. A lowered relative risk was present regardless of age at diagnosis and persisted during the entire follow-up period and into advanced ages. A case-control analysis within the cohort, and based on medical record data, indicated that a higher weight might be associated with a greater protective effect, as compared with a lower weight. Exposure to exogenous oestrogens was infrequent and could not have explained the present results. We conclude that persistent influence of oestrogens, notably of endogenous origin, can reduce the risk of hip fractures, and that this protective effect may be long-lasting and extend to advanced ages.


Oesophageal cancer in the Republic of Karakalpakstan.

Regional and temporal patterns of variation in the incidence of cancer of the oesophagus in the Central Asian republic of Karakalpakstan were analysed. Karakalpakstan (population about 1200,000) is an area with high rates of this disease. Incidence data within regions (data from 1988-1989), ethnic groups (data from 1987-1989) and calendar periods (data from 1973-1987) were available for analysis, with corresponding official population estimates. No significant difference was observed between rates in urban and rural environments, although significant regional variation was observed (P less than 0.05). The highest rate observed was in the Muinak, the northern region, with world age-standardized rates (ASR) of 125.96 for males and 150.65 for females. There was a very significant difference among ethnic groups (P less than 0.001). The ethnic group with the highest incidence was the Kazakh people, with an ASR of 68.0 in males and 86.3 in females. Incidence in the republic as a whole declined in the period from 1973 to 1987. Incidence of cancer of the oesophagus is still high in Karakalpakstan, despite the decline. Incidence is likely to be strongly related to factors associated with region of residence and with ethnicity.


Assessment of the spatial occurrence of childhood leukaemia mortality using standardized rate ratios with a simple linear Poisson model.

Reports of a suspected cluster of childhood leukaemia cases in West Central Phoenix have led to a number of epidemiological studies in the geographical area. We report here on a death certificate-based mortality study, which indicated an elevated rate ratio of 1.95 during 1966-1986, using the remainder of the Phoenix standard metropolitan statistical area (SMSA) as a comparison region. In the process of analysing the data from this study, a methodology for dealing with denominator variability in a standardized mortality ratio was developed using a simple linear Poisson model. This new approach is seen as being of general use in the analysis of standardized rate ratios (SRR), as well as being particularly appropriate for cluster investigations.


Body mass index and the initial manifestation of coronary heart disease in women aged 40-59 years.

A population-based case-control study was conducted to evaluate body mass as a coronary heart disease (CHD) risk factor among women 40-59 years of age. Cases were women aged 40-59 whose first manifestation of CHD was angina (No. = 133), nonfatal myocardial infarction (No. = 90), and sudden unexpected death (No. = 18) during 1960-1982. Two randomly selected controls were matched on age and time of the initial disease manifestation of the case. The adjusted relative risk for weight and body mass index respectively demonstrated a moderate association with all CHD as well as with angina, but no association with definite CHD (myocardial infarction or sudden unexpected death). To determine if the observed association between body mass index and angina was possibly attributable to differential misclassification bias (i.e. obese women were, in contrast to non-obese women, preferentially labelled as having coronary artery disease) data for angina were stratified by confirmed versus unconfirmed cardiac origin. In the unconfirmed angina analysis, the 75th percentile for weight contrasted with the 25th percentile was associated with a 50% increase in the risk of being labelled as having angina (adjusted odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.11-2.28), while a similar contrast for Quetelet Index was also associated with a nearly 2-fold increase in the risk of being labelled as having angina (adjusted OR = 1.74, 95% CI: 1.18-2.57).(ABSTRACT TRUNCATED AT 250 WORDS)


Demographic and behavioural correlates of high density lipoprotein cholesterol. An international comparison between northern Italy and the United States.

Recently published results of longitudinal follow-up studies conducted in the US have identified high density lipoprotein (HDL)-cholesterol as an independent and strong predictive factor for coronary heart disease (CHD). Some inconsistencies in this association have been found when geographical comparisons were done, which could be explained by hypothesizing differences in population HDL-cholesterol determinants. We carried out a comparative analysis of demographic and behavioural correlates of HDL-cholesterol between Northern Italy and the US, two countries with well-known differences in CHD risk and HDL-cholesterol levels. The study was conducted on representative samples of these two countries (MONICA Project-Area Brianza for Northern Italy and NHANES II for the US) and used comparable methodologies for data collection and statistical analysis. Results indicate that gender, age, body mass, cigarette smoking and alcohol consumption are independently associated with HDL-cholesterol in both populations; physical activity is positively, but not significantly, associated with HDL-cholesterol mean levels, and education achievement is independently associated only in the American sample. The comparison of the magnitude of the multivariate regression coefficients between the two studies suggests similar functional relationships for most of the correlates considered. The small, albeit significant, discrepancies found for body mass and smoking status could be related either to some methodological inconsistencies between the two surveys, or to possible effects of other covariates, not available to be tested in this study, like dietary habits. Moreover, HDL-cholesterol mean level differences between populations could be also due to differences in the prevalence of the examined correlates.


Prevalence and control of hypertension in a large cohort of occupationally-active Israelis examined during 1985-1987: the Cordis Study.

In view of the many changes in the approach to the detection and management of hypertension that have occurred, the paucity of current data on this subject in Israel limits the possibilities of making international comparisons or evaluating trends. This study contributes recent information on the occupationally-active population. Between 1985 and 1987, blood pressures were measured and interview data obtained on awareness and treatment of hypertension in a sample of 3677 male and 1573 female employees in 21 Israeli industries, examined in the CORDIS Study. In the age group 35-64 years, the age-standardized prevalence of hypertension (greater than or equal to 160/95 mm Hg or treated) using the same standard population as the WHO MONICA Study was 17.1% for men and 16.1% for women. The prevalence for men was somewhat below the median country compared with the MONICA centres, whereas for women it was closer to the median. Marked ethnic differences were evident, with those of Western origin having the highest prevalence, and those of Asian origin, the lowest. Of the hypertensives, 35.6% of the men and 33.3% of the women were unaware of their condition. Among men aware, 82.8% were receiving treatment and 59.8% of them were under control; the corresponding percentages for women were 86.2% and 72.8%. Older people were more likely to be aware of their hypertension and receiving treatment. Beta-blockers and diuretics were the predominant drugs of choice.(ABSTRACT TRUNCATED AT 250 WORDS)


Habitual dietary calcium intake and blood pressure change around the menopause: a longitudinal study.

In a 10-year follow-up study, blood pressure and dietary intake were measured annually in 167 healthy perimenopausal normotensive women. Their initial ages ranged between 49 and 56 years and habitual calcium intake between 560 and 2580 mg/day (mean 1110 mg/day); they lived in the mixed rural/industrial community of Ede, the Netherlands. The longitudinal design provided an opportunity to study the 'natural history' of blood pressure and the effect of dietary calcium during and after the period of ovarian failure. For data analysis, person-time experience was divided into three menopausal periods. Based on years relative to menopause three menopausal cohorts were created starting 2 years before, 2 years after and 6 years after menopause, each was followed for 4 years. Changes in systolic (SBP) and diastolic blood pressure (DBP) during the menopausal periods were adjusted for change in body mass index and other relevant variables in multiple regression analysis. An average decline in SBP of 6 mm Hg was observed in the period of 2 years before menopause to 6 years after menopause, and an increase of almost 5 mm Hg in the period between 6 and 10 years after menopause. A significant change in DBP was not observed. Neither changes in, nor the absolute level of, calcium intake showed any relevant association with blood pressure change. Ovarian failure seems to reverse temporarily the increase in blood pressure due to aging. The results do not suggest that a habitual calcium intake exceeding 800-1000 mg/day (the current Recommended Daily Allowance for adults) is effective in preventing hypertension during the peri- and postmenopausal period.


Changing trends in mortality among New Mexico's American Indians, 1958-1987.

Health care availability and living conditions have improved substantially for American Indians in New Mexico over the past quarter century. To investigate the impact of these changes on health statistics, we examined mortality data collected from 1958 to 1987 for American Indians in the state. We analysed the data for all causes of death combined and for specific causes, and compared these data with figures for nonHispanic whites in the state. Age-adjusted mortality rates were calculated for 5-year periods for each ethnic-gender group, using denominators from US Census reports. Mortality rates for all causes combined did not improve significantly for American Indian males from 1958 to 1987, although the rates for American Indian females showed an 8% decline. Infectious disease-related mortality rates for American Indians decreased dramatically over the 30-year study period; however, mortality rates for cancer and diabetes increased over the 30-year period. Mortality rates for injuries and alcoholism among American Indians increased greatly from 1958 to 1977 and then declined later in the study period, but they were consistently higher than rates for whites. The study indicates that several chronic diseases remain of major public health importance for New Mexico's American Indian population.


Compliance with a 12-month assessment in an elderly cohort participating in a preventive intervention study: the San Diego Medicare Preventive Health Project.

Non-compliance in long-term cohort studies contributes to bias in the estimation of study parameters and loss of power in hypothesis testing. This paper identifies baseline factors associated with non-compliance in a 12-month health assessment among elderly participants in the San Diego Medicare Preventive Health Project, a randomized preventive intervention study. A non-complier was defined as a study subject contacted by telephone by study personnel to schedule an appointment for the 12-month health assessment but who would not or could not attend. Of the almost 1600 contacted subjects, 14.1% did not participate in the evaluation. Using logistic regression, non-compliance was found to be associated with older age, intervention group assignment, nonsingle family residence, no alcohol use, and, to a lesser extent, depression. No interactions between group assignment and other baseline factors were detected. These results may be useful in designing cohort maintenance strategies where greater resources may be devoted to participants at higher risk of non-compliance and attrition.


Use of positive-negative deviant analyses to improve programme targeting and services: example from the TamilNadu Integrated Nutrition Project.

This paper describes the characteristics of southern rural Indian children who grow best (positive deviants) and worst (negative deviants) as compared to median growers. A 100 each of positive and negative deviants and 120 median growers were selected after analysing the 12-month growth patterns (weight-for-age) of 2954 children enrolled in the TamilNadu Integrated Nutrition Project (TINP), a major health and nutrition intervention project covering nearly one million children in rural south India. The determinants of poor growth that have been left unaddressed by 6 years of TINP exposure are delineated to address the question of what more needs to be done. Further, the rationale for differential targeting of services to negative deviants and to median growers is discussed, as are the implications for programme evaluation. Data indicate that the next generation of projects targeted at the most needy (negative deviants) should address the issues of gender discrimination in childcare, of breastfeeding, of diarrhoeal disease, and of maternal empowerment. Such interventions will, however, not improve the growth of median growers in the direction of positive deviance. Instead, programmes targeted at the median growers need to support the hygienic use of nonbreast milk supplements. Improving family wealth will also improve the nutritional status of the median growers, but less so than for the negative deviants.


Space time clustering of births in SIDS: do perinatal infections play a role?

The aetiology of sudden infant death syndrome (SIDS) remains uncertain; many causal pathways have been proposed. In this paper we have examined firstly the variation in the risk of SIDS with age, month of death and month of birth; and secondly the space time clustering of SIDS deaths, and, separately, space time clustering of their births. Data were obtained from the Office of Populations, Censuses and Surveys on all certified SIDS deaths in the period; children were assigned grid references for the address of birth and of death. Data on number of births were abstracted from published material. A log-linear modelling technique was used to investigate the separate effects of age, month of death and month of birth on the risk of SIDS. The Knox method was used to investigate space time clustering of deaths and of births of children who died of SIDS. Separate, statistically significant effects were found for age, month of death and month of birth. There was minor space time clustering of SIDS births and deaths at large time and space intervals, and a marked space time clustering of births in short space time intervals in the first quarter of the year. The finding of an effect of month of birth on the risk of SIDS, and of space time clustering of births suggest that a perinatal hazard--possibly of infectious origin--may play a role in the aetiology of SIDS.


Mother's education and perinatal problems in Finland.

This study using nationwide data expands a previous study from one area in Finland. The purpose was to study how perinatal problems (mortality, short gestation, low birthweight and low Apgar scores) vary by mother's social class, which is measured by level of education. Outcomes of all births in the 1987 Medical Birth Register were linked to the 1988 National Education Register with gives the estimated number of years of completed education. In unadjusted analyses, the lowest educational groups (less than 9 years) had the worst results for outcomes other than neonatal mortality. Results in the two highest educational groups (greater than or equal to 13 and 12 years of education) were similar and if anything, better in the second highest group. Excluding twins and adjusting for confounding variables (age, parity, county, urbanization of residence) by logistic regression analysis did not alter the results much. Adjustment for possible mechanisms correlated with social class (marital status, smoking, time of first antenatal visit) decreased the higher occurrence of low birthweight infants in the low educational groups. Reported previous miscarriages were more common in the higher educational groups. Based on the available background characteristics one would expect to have found the usual social gradient in perinatal problems to have persisted between the two highest educational groups. Further studies on factors causing the plateau in the gradient between these groups might be useful.


Ancestral origin of insulin-dependent diabetes in Mexican-Americans.

To test the hypothesis that insulin-dependent diabetes mellitus in the Mexican-American population is due to Spanish genetic admixture, we obtained ancestral information on 106 Mexican-American families with an insulin-dependent diabetic index case and 80 Mexican-American control families from 1987 to 1991. The Mexican states of origin were available on 395 grandparents of the insulin-dependent diabetic index cases and 291 grandparents of the controls. Analysis of the individual states of origin revealed that there were significantly more Mexican-American grandparents of diabetic index cases from the states of Jalisco and Michoacan when compared to the control families (31% and 16% diabetic versus 22% and 11% controls respectively, P less than 0.01). The states of Zacatecas and Durango had a lower frequency of diabetic grandparents as compared to controls (6% diabetic versus 12% controls, P less than 0.001). Analysis of the origin by Northern and Southern states of México revealed a significant decrease in the number of grandparents of the insulin-dependent diabetic cases from the Northern regions of México, 19.5%, versus 32% in controls, (P less than 0.001). These data indicate that the grandparents of the insulin-dependent diabetic index cases originate from states and regions of México which were those of the early entry of the Europeans. These data thus support the hypothesis that insulin-dependent diabetes mellitus in the Mexican-American population may be due in significant part to an original genetic contribution from the Spanish-European population.


Prevalence of diagnosed diabetes in circumpolar indigenous populations.

The prevalence of diagnosed diabetes in several genetically closely related indigenous populations in the circumpolar arctic and subarctic regions of Russia, Alaska and Canada is compared. The age-standardized (to the IARC's hypothetical world population) prevalence ranged from 1.8/1000 among the Chukchi and Eskimo of Chukotka, 3.6 and 7.9/1000 among the Eskimos/Inuit of the Canadian Northwest Territories (NWT) and Alaska respectively, 7.1, 9.3 and 18.6/1000 among Athapaskan Indians in the NWT, Yukon and Alaska respectively, to a high of 22.7/1000 among the Aleuts in Alaska. All are below the US all-race prevalence of 23.5/1000 and far below the extreme high prevalence reported from many North American Indian tribes. As a group, such arctic and subarctic peoples have a much shorter and less intense history of European contact and acculturation. Environmental factors are also likely to be responsible for the current differences between these indigenous populations in the circumpolar region, assuming that they share susceptibility genes for diabetes inferred from their close genetic relationships based on markers in other loci. Formal surveys of glucose tolerance and potential risk factors such as diet, physical activity, obesity, insulin resistance and genetic admixture in the circumpolar region would improve knowledge of the aetiology of diabetes in genetically and culturally diverse human populations.


Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma.

A case-control study has previously been reported of asthma deaths in people aged 5-45 years who had a hospital admission for asthma (the index admission) in New Zealand during 1981-1987. The study has been re-analysed to examine the association between markers of asthma severity and risk of asthma death or hospital admission; patients prescribed fenoterol were excluded from this re-analysis because of the previously reported interaction between fenoterol, asthma severity, and asthma deaths. The re-analysis included 39 patients who died of asthma during the 12 months after their index admission, 226 patients who had a readmission for asthma during the 12 months after their index admission, and 263 controls chosen from all index admissions. An admission in the previous 12 months was the strongest marker of subsequent risk of death (odds ratio (OR) = 3.5, 95% confidence interval (CI): 1.8-6.9, P less than 0.01), and was also a strong marker of subsequent risk of readmission (OR = 3.0, 95% CI: 2.1-4.2, P less than 0.01); the risk increased with the number of previous admissions. Three or more categories of prescribed asthma drugs was also associated with subsequent death (OR = 1.7, 95% CI: 0.9-3.3, P = 0.13) or readmission (OR = 1.9, 95% CI: 1.3-2.7, P less than 0.01); prescribed oral corticosteroids was only weakly associated with subsequent death (OR = 1.3, 95% CI: 0.6-2.8, P = 0.59), but was more strongly associated with subsequent readmission (OR = 1.9, 95% CI: 1.2-2.8, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiological study of the cardiovascular effects of carbon disulphide.

In an extensive health survey 115 male viscose rayon workers exposed to carbon disulphide (CS2) and 76 referents not exposed to this chemical were interviewed using the WHO cardiovascular questionnaire and responded to a self-administered questionnaire. A 12-lead ECG was taken and coded using the Minnesota code. Blood pressure (BP) was measured electronically and blood was examined for lipoproteins. In the viscose rayon factory the working conditions had not changed since 1932. Personal monitoring performed in 17 jobs, showed exposures varying from 4 to 112 mg/m3. For each individual a CS2 cumulative exposure index (CS2 index) was calculated. There were no significant differences between exposed and referents concerning the prevalence of angina, history of myocardial infarction, intermittent claudication and ECG signs of ischaemia. Blood pressure, low density lipoprotein (LDL)-cholesterol and the apolipoproteins A1 and B rose while high density lipoprotein (HDL)-cholesterol, the HDL-cholesterol/apolipoprotein A1 and the LDL-cholesterol/apolipoprotein B ratios decreased significantly with increasing exposure. Adjustment for age, body mass index, smoking, alcohol consumption, stress and tension at work, shift work, noise exposure and educational level in multiple linear regression analysis showed significant effects of the CS2 index on systolic BP, diastolic BP, cholesterol, HDL-cholesterol, LDL-cholesterol, apolipoprotein A1, apolipoprotein B, the LDL cholesterol/apolipoprotein B and HDL cholesterol/apolipoprotein A1 ratios; there were no significant effects on the triglycerides.


Influence of individually estimated portion size data on the validity of a semiquantitative food frequency questionnaire.

Using data from a Danish dietary validity study, we evaluated the influence of including individually estimated portion size data on the validity of a semiquantitative food frequency questionnaire. A total of 144 subjects, aged 40-64 years were included. Correlation coefficients and classification of subjects into quintiles according to their intake of foods and nutrients were used to compare questionnaire data, with and without individually estimated portion size data, with data obtained by 2 x 7 days weighed diet records. For men, the mean correlation coefficient for food group comparisons was 0.47 when information about individually estimated portion sizes for food items that do not come in natural units was included in the analysis. Using a common average portion size reduced the mean correlation coefficient to 0.45. For women, similar changes were observed (0.36 to 0.35). For nutrients the mean values for the comparison changed from 0.51 to 0.49 and from 0.39 to 0.40 for men and women, respectively. For both men and women the classification into quintiles according to their intake of foods and nutrients showed only minor differences. We conclude that little extra information was gained by including individual portion size information for food items that do not come in natural units. This may reflect that portion sizes are of minor importance compared with frequencies or that the relevant individual portion sizes were not estimated correctly.


Nonoccupational determinants of blood lead concentrations in a general population.

We investigated the influence of various nonoccupational factors on blood lead levels (PbB) in a sample from the general population of southern Germany. Some 1703 men and 1661 women, aged 28-67 years, were examined in the first follow-up examination of the MONICA Augsburg cohort study in 1987-1988. Their mean PbB was 90 micrograms/l (SD:35.9) for men and 65 micrograms/l (26.4) for women. Only 5% of the men and 1% of all women exceeded a PbB level of 150 micrograms/l indicating low-level lead exposure in this population. Blood lead was significantly associated with haematocrit values (P < 0.001) and the shape of this association was curvilinear. Per gram of alcohol consumed, intake of beer had a lower impact on PbB than wine, presumably due to differential lead content in these alcoholic beverages. The alcohol-PbB associations were stronger for women than for men. The impact of smoking was generally moderate but again more prominent in women. In particular, the covariate adjusted odds ratios for women of childbearing age (28-47 years) to have PbB levels above 100 micrograms/l were 2.5 (95% confidence interval (CI): 1.3-4.7) for smoking versus non-smoking females, 2.6 (95% CI: 1.1-6.0) for women drinking up to 40 g alcohol/day compared to abstainers, and 8.9 (95% CI: 3.2-25.1) for those drinking more than 40 g alcohol/day. Other factors like age, body mass, rural place of residence, and education or job position, had only minor influences on PbB. We conclude that haematocrit values should always be considered as potential confounders in low-level lead exposure research. High alcohol consumption and cigarette smoking are strongly related to elevated blood lead concentrations in the general population and may thereby convey additional health hazards such as impaired child development or blood pressure elevations. This deserves proper public health recognition [corrected].


Estimation of leprosy prevalence in Bago and Kawa townships using two-stage probability proportionate to size sampling technique.

Two surveys to estimate leprosy prevalence using two-stage probability proportionate to size sampling technique were conducted in Bago and Kawa townships. A total of 3519 and 3739 individuals were examined in each township. The two surveys were finished within 25 (Bago) and 30 (Kawa) working days at a cost of Kyats 10,000 (US $1500) for each survey. The estimated leprosy prevalence obtained in Bago was 9.95 per 1000 population (95% confidence interval (CI): 7.11-12.78) and in Kawa it was 12.04 per 1000 population (95% CI: 8.85-15.22). A total of 30 (Bago) and 34 (Kawa) new leprosy cases were detected in the two surveys. Grade I disability was seen to be 20% in Bago and 18.78% in Kawa, whereas grade II disability was 17.14% in Bago and 15.56% in Kawa.


Assessing the extent of the HIV epidemic in Sweden, using information on the extent to which people who develop AIDS are already known to be HIV infected.

In Sweden, cases of both HIV infection and AIDS are registered. By looking at the extent to which people who develop AIDS are already known to be HIV-infected, we can assess the coverage of the HIV registration. It was found that virtually all those who were infected by injecting themselves with drugs, blood transfusions, blood products or congenitally were already known to be infected when AIDS developed. However, when homosexual or heterosexual transmission had occurred, 20.5% and 33.3% respectively of these cases were not previously known. Working with different assumptions regarding the development of the epidemic, we find that the true number of sexually infected people is roughly twice the number of registered HIV-infected people in these groups. Our estimate is that between 3300 and 6300 people were infected with HIV in Sweden up till the end of 1990.


A retrospective study of childhood mortality and spontaneous abortion in HIV-1 infected women in urban Malawi.

HIV infection in pregnant women has been shown to have an adverse effect on the fetus and newborn. We undertook this study to examine the adverse effect of maternal HIV-1 infection on two outcomes of the previous pregnancy, as reported by the women: childhood mortality under the age of 3 years and spontaneous abortion. Some 6605 consecutive women who presented to a large urban hospital in Malawi for antenatal care were interviewed and tested for HIV-1 antibody. Of these 4229 (64%) were multiparous and 833 (19.7%) were seropositive for HIV-1. A history of under-3 mortality of the previous pregnancy was more common in HIV-1 seropositive than HIV-1 seronegative women (35% versus 15%, P less than 0.001). In the previous pregnancy, death of infants and children under 3 years was 77 and 119 per 1000 respectively for HIV-1 seronegative mothers, but increased to 171 and 292 per 1000 in infants and children under 3 years for HIV-1 seropositive mothers. History of child mortality was independently associated with positive HIV-1 serology, positive syphilis serology, low socioeconomic status, young age and not having married. There was no correlation between history of child mortality and reported symptoms of HIV/AIDS by infected mothers, except for history of tuberculosis which was reported more often by mothers whose child had died (4% versus 1%, P less than 0.036).(ABSTRACT TRUNCATED AT 250 WORDS)


Predictors of poliomyelitis case confirmation at initial clinical evaluation: implications for poliomyelitis eradication in the Americas.

In 1985, the Pan American Health Organization adopted the goal of eradication of poliomyelitis from the Americas by 1990. Strategies to accomplish this included high vaccination coverage, aggressive outbreak control, and active surveillance for acute flaccid paralysis (AFP). Although the sensitivity of AFP surveillance for detecting paralytic poliomyelitis cases is high, studies have shown the specificity to be low. In 1990, 2497 notified cases of AFP were investigated in the Americas of which 2146 had stool specimens collected. However, only 18 were confirmed as poliomyelitis by isolation of wild poliovirus from stool specimens, 71 were classified as being compatible with poliomyelitis. Cases of AFP due to causes other than poliomyelitis result in extensive but unnecessary outbreak control measures. To predict, at initial clinical evaluation, the likelihood of future confirmation as a case of poliomyelitis, likelihood ratios (LR) were calculated for different combinations of clinical characteristics of AFP cases (249) from Mexico in 1989 and 1990. The best predictors in a child with AFP were proximal muscle involvement which progressed '4 days together with fever at onset of paralysis, and proximal and unilateral involvement with either fever at onset or paralysis which progressed '4 days. The odds would increase by 12 that the child would eventually be confirmed as poliomyelitis (19), based on a stool culture positive for wild poliovirus (95% confidence interval (CI) 2.6-55.9). A guide for use in the field is proposed whereby local health officials, often with little training in neurological evaluation, can predict at initial clinical examination the likelihood that an AFP case will subsequently be confirmed as poliomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiological features of an outbreak of diphtheria and its control with diphtheria toxoid immunization.

An outbreak of diphtheria primarily involving adults occurred in seven townships and one farm in Jiangling county, Hubei, China from September 1988 to January 1989. Of the 103 reported cases, 80 were aged over 16 years, and there were two deaths. One hundred cases were reported in Jingzhou and its surrounding townships, only three occurred in townships distant from Jingzhou. The incidence and case fatality rates were 11.54/100,000 and 1.94% respectively. Twenty-one strains of diphtheria bacillus were isolated from 68 patients. A special immunization programme using adsorbed diphtheria toxoid was conducted 1 month into the outbreak, following which the incidence declined rapidly. Five vaccinees subsequently developed diphtheria.


Risk factors for the transmission of diarrhoea in children: a case-control study in rural Malaysia.

In response to a recorded increasing incidence of diarrhoea in Tumpat District, Malaysia, a case-control study was performed to identify modifiable risk factors for the transmission of diarrhoea, in children aged 4-59 months. Ninety-eight pairs of children, matched on age and sex, were recruited prospectively from health centres. Exposure status was determined during a home visit. Interviewers were 'blinded' as to the disease status of each child. Odds ratios were measured through matched pair analysis and conditional logistic regression. Risk factors for diarrhoea identified were: reported--drinking of unboiled water, storage of cooked food before consumption and bottle feeding; and observations--animals inside the house and absence of washing water in latrines. Water quality, source of drinking water, reported hand washing behaviour, indiscriminate defecation by children, cup use and the absence of a functional latrine were not associated with diarrhoea. Nonsignificant associations were found for: accessibility of washing water source, type of water storage container and use of fly covers for food.


Comparative accuracy of implant impression procedures.

In this study, four impression procedures were assessed for accuracy in a laboratory model that simulated clinical practice. The accuracy of stone casts with brass implant analogs was measured against a standard framework. The fit of the framework on the casts was tested by manual and visual judgment and by microscopic measurement. The measurements supported the clinical judgments. When acrylic resin was used to splint transfer copings in an impression, all casts were acceptable and were more accurate than the best of the two other procedures, which did not use an acrylic resin splint. When an impression material was used to orient the transfer copings, the accuracy was better if undercut copings remained in the impression. When impressions were made by removing an impression from smooth transfer copings and replacing the copings in the impression, the majority of casts were unacceptable.


Use of a collagen barrier to enhance healing in human periodontal furcation defects.

Guided tissue regeneration procedures are intended to selectively favor healing by the periodontal ligament tissues. However, in most studies of the efficacy of guided tissue regeneration, nonresorbable barriers and membranes have been used, necessitating their surgical removal after a time. The present study employed a resorbable collagen barrier to treat Class II function invasions. The results of this treatment were compared with the results of conventional therapy. For most clinical parameters, there was no statistically significant difference in the results of treatment with or without collagen membranes. Sites treated with a collagen barrier did exhibit statistically significant improvement in probing depth and horizontal osseous support; however, these findings cannot be attributed entirely to the placement of the collagen membrane.


Reconstruction of bone on facial surfaces: a series of case reports.

To rebuild the damaged periodontium to its original form, it would be ideal not only to cover the denuded root surfaces with soft tissue, but also to reconstruct the cortical plate. This paper presents four cases in which osseous grafts and guided tissue regeneration, along with root surface conditioning, were used to encourage growth of new facial bone. Some degree of success was achieved in each case.


Surgical reconstruction of the interdental papilla: case report.

Historically, periodontal treatment has been aimed more at the preservation and restoration of health to the periodontium than at the esthetic outcome of treatment. However, recent advances have enhanced the periodontist's ability to address esthetic concerns. To date, treatment of lost or collapsed interdental papilla has been largely unsuccessful. A case report is presented to demonstrate a technique by which a collapsed interdental papilla can be surgically reconstructed. The technique combines principles of Abram's roll technique for ridge augmentation with Evian's papilla preservation technique.


Achieving ideal esthetics in osseointegrated prostheses. 1. Multiple units.

This article describes two new abutments that are intended to enhance the esthetics and function of the implant prosthesis while keeping it in harmony with the periodontium. Part 1 discusses the EsthetiCone, designed for use with multiple-unit restorations, which allows subgingival placement of porcelain for maximal esthetics. Unlike traditional abutments, the EsthetiCone is placed 4 to 6 weeks after the fixture is uncovered. Therefore, the size and type of abutment are chosen by the restorative dentist, rather than by the surgeon. Guidelines for abutment selection and placement are provided in this paper.


Enhancement of the damaged edentulous ridge to receive dental implants: a combination of allograft and the GORE-TEX membrane.

A severely damaged edentulous ridge frequently obviates the placement of dental implants or results in placing them at an angle that compromises the prosthetic restoration. This paper demonstrates the repair of severely resorbed edentulous ridges by a combination of bone allografting and the placement of a barrier membrane. The damaged edentulous ridge is treated first in this two-stage process. The implants are then installed at a second surgery.


Comprehensive evaluation of a Thorotrast patient: an overview.

For several decades, thousands of people received Thorotrast during the course of angiography and other radiologic procedures. Eventually, as the hazards of this radioactive, radiographic contrast agent became apparent, research was initiated to further evaluate its associated adverse effects. In 1988 and 1989, Charles W. Mays, together with colleagues at a variety of sites, developed a detailed protocol for the comprehensive postmortem evaluation of one subject who had been administered Thorotrast 36 y previously. This case represents the first holistic approach to the analysis of Thorotrast in a whole body, simultaneously assembling clinical and autopsy findings with dosimetric, radiochemical, autoradiographic, and molecular evaluations.


Portable 220Rn detector used to assess Thorotrast exposure.

Patients who are exposed by injection to the radiological contrast medium Thorotrast (232ThO2) had been considered by early researchers to be an unfortunate but important model of alpha-particle carcinogenesis in the lung as well as liver and bone marrow because they continuously exhale 220Rn, in the breath of Thorotrast patients and (as the first step to lung dosimetry) to investigate the relationship between exhaled 220Rn activity concentration (Bq L-1) and 232Th body burden. Results revealed that reliable estimation of 232Th burden by 220Rn measurement is possible because a fairly good correlation was obtained between 220Rn in the breath and the known quantity of 232Th in the body. Mean 220Rn activity concentration in the breath was 9.21 Bq L-1 g-1 of 232Th deposited in the liver and spleen. This value was very close to that published for German patients. Our data and those of other investigators indicate that apparent discrepancies in mean 220Rn activity concentration among previous studies was caused by using different 228Th:232Th activity ratios.


Clinical consequences of Thorotrast in a long-term survivor.

Thorotrast, a colloidal suspension of 252Th dioxide, was widely used as a radiographic contrast medium for more than 25 y after its clinical practice introduction in 1930. Its excellence as a contrast medium was ultimately eclipsed by its long-term associated morbidities, and its use essentially ended by 1954. This case history presents the clinical events in the last 10 y of life in a patient injected with Thorotrast in 1953. This patient developed three previously described Thorotrast-associated morbidities: pneumococcus sepsis due to functional asplenia and reticuloendothelial system blockade, an enlarging Thorotrastoma (inflammatory mass) at the injection site, and a fatal blood dyscrasia. In addition, she developed three clinical syndromes where a Thorotrast association may exist. She suffered from severe spinal column osteoarthritis and vertebral collapse. An abnormal bone-density measurement implies the presence of radiodense radioactive thorium or its degradation products as potentially responsible. She had evidence of chronic immune system disregulation with immunoglobulin excess, auto antibodies, and cell-mediated immunity deficiency. This condition is similar to that found in patients infected with human immunodeficiency virus and may suggest a shared etiology in reticuloendothelial system damage. Lastly, she developed dense bilateral cataracts. This case history illustrates the temporal relationship of a variety of symptoms. Discussion is directed at review of previous data and support for new associations.


Whole-body pathologic analysis of a patient with Thorotrast-induced myelodysplasia.

An autopsy was performed on a 72-y-old Caucasian female who had received a carotid artery injection of thorium dioxide in 1953. The body was dissected in such a manner as to provide for radiobiological evaluation as well as to determine histologically the distribution of Thorotrast in the tissues and its complications. Thorotrast was identified within the liver, spleen, lymph nodes, bone marrow, and surrounding the right carotid artery (the injection site). The cause of death was gastric hemorrhage complicating pancytopenia secondary to refractory anemia with excess of blasts (myelodysplastic syndrome).


Alteration of the c-fms gene in a blood sample from a Thorotrast individual.

We analyzed six different tissue DNA samples from a leukemic individual who received an injection of Thorotrast for alterations in proto-oncogene or tumor-suppressor gene structure. Our examination of the DNA indicated an alteration of the c-fms gene in the blood sample from this individual. This locus showed a deletion in which the 3' end of the deleted region maps between exons 11 and 12. In this particular case, the type of leukemia is unknown but myeloid leukemia is a neoplasm associated with individuals injected with Thorotrast. It is possible that the alteration in the c-fms gene of this individual is a consequence of the radiation exposure. No apparent alterations in the c-mos gene were observed in any of the tissues from the individual. This is in contrast to previous studies that described alterations in methylation patterns associated with the c-mos locus in radium-exposed individuals. A number of the individuals exposed to radium also had alterations of the retinoblastoma gene while no such alterations were observed in any tissue DNA samples from this Thorotrast case. It is possible that our inability to detect alterations of the c-mos and retinoblastoma gene may be attributable to the nature of alpha-emitting radionuclides or their distribution, or to the limited set of tissues available for analysis.


External gamma-ray counting of selected tissues from a Thorotrast patient.

Results of gamma-ray measurements of selected tissues from a patient who was injected with Thorotrast almost 36 y ago are reported. The purposes of this study were: 1) to determine the relative tissue distribution and activities of specific radionuclides in the 232Th decay chain, specifically 228Ra (as measured by 228Ac), 212Pb, and 224Ra (measured directly and as measured by 212Pb), and 2) to evaluate the level of radioactive disequilibrium among the daughter products. The spleen and liver had the highest concentrations of radioactivity. Bone also appears to be a long-term sink for 232Th daughter products based on estimates from a small portion of one rib. Larynx and esophagus contained measurable activity, which may have been due to their proximity to the "Thorotrastoma." Radioactivity in the remaining measured tissues were low, as expected. Secular equilibrium could be demonstrated in bone, pancreas, larynx, esophagus, and breast. Significant disequilibrium was observed for spleen, liver, kidney, and red blood cells. Radioactivity measurements reported here will be useful in estimating radiation doses to selected tissues. Such dose estimates are valuable in refining current risk estimates (e.g., liver) and in identifying tissues at risk for further epidemiologic studies. These results, while consistent with other published studies, should be interpreted with caution since measurements were made on only one patient.


Microdistribution and microdosimetry of thorium deposited in the liver.

The distribution of thorium in the liver of a patient 36 y after injection with Thorotrast was examined with autoradiographic and scanning electron microscope backscatter image techniques. Autoradiographic examination of randomly selected histologic sections of the liver showed a total alpha activity calculated at 33.7 Bq g-1, with the highest concentration of alpha activity sequestered in subcapsular scare tissue. Subcapsular scare tissue received 4.8 cGy d-1 of alpha radiation, periportal areas were accumulating 1.4 cGy d-1, and the hepatic cord areas 0.09 cGy d-1 of alpha radiation at the time of death. The concentration of dose in periportal areas correlates with higher incidence of bile duct tumors (than hepatocellular carcinomas) found in patients exposed to Thorotrast. The backscatter technique was demonstrated as useful for identifying thorium in liver specimens.


The distribution of Thorotrast in human bone marrow: a case report.

Samples of bone containing cellular and fatty bone marrow were removed at autopsy from the body of a woman who, following an automobile accident, had been injected with approximately 25 mL of the radiographic contrast medium Thorotrast. The woman survived for 36 y after the accident and died at age 72 y following bone marrow failure. The samples were analyzed to determine their thorium content by x-ray fluorescence and by image analysis. In addition, Thorotrast was visualized in the different bones examined by light microscopy and by backscattered electron imaging with a scanning electron microscope. The results showed Thorotrast to be largely restricted to areas of cellular bone marrow. In such regions, Thorotrast was present throughout the marrow tissue and was also concentrated within cells that were commonly aggregated within focalized areas of the marrow. Overall the results suggest a rather uniform pattern of Thorotrast uptake by the red bone marrow at different skeletal sites. Significant deposits of Thorotrast were not found in fatty yellow marrow. We conclude that Thorotrast-derived risk estimates for human leukemia following high LET, alpha irradiation may be used for calculating the risks of alpha exposure, but with caution.


Measurement of thorium isotopes and 228Ra in soft tissues and bones of a deceased Thorotrast patient.

The whole body of an individual injected with Thorotrast 36 y prior to her death was analyzed for 232Th, 228Ra, 228Th, and 230Th. Measurement of these isotopes in all tissues of the body will provide data necessary to caculate the radiation dose to individual tissues and to evaluate the risk potential associated with deposition of thorium and progeny in humans. The tissues were ashed, dissolved in acid, and the thorium isolated by ion exchange and electrodeposition. The 228Ra was determined by measuring the 0.991-MeV gamma rays associated with decay of the 228Ac daughter. It was estimated that almost all of the 232Th from the original injection was retained in the body, mostly in the tissues of the reticuloendothelial system. A total of 28 kBq (0.76 microCi) of 232Th was measured in the soft tissues and bones. The body also contained 13 kBq 228Ra, 12 kBq 228Th, and 3.9 kBq 230Th. A Thorotrastoma contained about 3.5% of the total activity. Excluding the Thorotrastoma, approximately 45% of all the activity (232Th, 228Ra, 228Th, and 230Th) was retained in the liver, 13% in the spleen, 2% in muscle, 1% in skin, slightly less than 1% in the respiratory tract, 4% in all other soft tissues, and 33% in the skeleton (bone and bone marrow). Sixty to 80% of the thorium activity in bones containing red marrow was located in the marrow. Bones containing yellow marrow had less than 40% of the thorium activity in the marrow. Highest concentrations were found in the hepatic and other abdominal lymph nodes, spleen, hilar lymph nodes, liver, trachea, and bone. Approximately 60% of the 228Ra formed from the decay of the 232Th had been excreted from the body. The 228Ra and 228Th were in approximate equilibrium throughout the body.


Distribution and dosimetry of Thorotrast in USUR case 1001.

The distribution of radioactivity and the associated doses were evaluated postmortem for USUR Case 1001, a female who had been injected with Thorotrast some 36 y prior to death. The distribution was determined for four nuclides: 232Th and its decay products, 228Ra and 228Th; and 230Th, a contaminant associated with Thorotrast. More than 90% of the activity was associated with the reticuloendothelial system. Approximately 32% of the total activity was found in the total skeleton (mineral bone and bone marrow), which is somewhat higher than expected from the literature. The 44% found in the liver and 12% in the spleen were somewhat lower than expected. This difference may be attributable, in part, to the initial deposition as influenced by colloidal particle size and to the radiation-induced hyposplenism, splenic atrophy, and slight hepatic atrophy observed at autopsy. In addition, roughly 3% of the activity was found in the Thorotrastoma and surrounding carotid artery tissue. Estimated lifetime absorbed doses from the 232Th series were 15 Gy to the liver, 121 Gy to the spleen, 4 Gy to the skeleton, and 16 Gy to the Thorotrastoma. Comparable dose equivalents to these tissues are 300, 2420, 80, and 320 Sv, respectively, assuming a quality factor of 20 for alpha irradiation.


Cancer risk following exposure to Thorotrast: overview in relation to a case report.

Radioactive measurements and histopathologic findings are described in a patient administered Thorotrast, a radiographic contrast agent, 36 y prior to death and compared with cancer risks noted in epidemiologic studies. This person [designated as U.S. Uranium Registry (USUR) Case 1001] had prearranged for donation of her body to the USUR and the National Cancer Institute for study. Elevated levels of radioactivity were noted in those organs in which excess cancers have been reported in epidemiologic surveys of Thorotrast-exposed subjects. Hepatic tissue in USUR Case 1001 was estimated to have received an average lifetime absorbed dose of 16.2 Gy, based on radiochemical analyses, consistent with the high risks for liver tumors reported in all studied populations. Thorotrast was present throughout the bone marrow of USUR Case 1001, who died secondary to complications of refractory anemia with excess blasts (RAEB). Elevated risks for acute myeloid leukemia have been noted in Thorotrast patients, and more recently, cases of RAEB and RAEB in transformation have been reported. The thorium decay series includes the bone-seeking radionuclides 224Ra and 228Ra, which have been associated with high risks for osteosarcomas, although the association between Thorotrast and bone cancer is not as convincing. The skeleton of USUR Case 1001, however, contained significant levels of radioactivity. Other tissues evaluated in USUR Case 1001 included lung, eye, kidney, and breast, which did not contain elevated levels of radioactivity.


Evaluation of reduction-mediated labelling of antibodies with technetium-99m.

Monoclonal antibodies can be labelled with technetium-99m by prereduction of the antibody with 2-mercaptoethanol, then reduction of pertechnetate with an aliquot of a stannous kit, resulting in greater than 97% labelling without the need for further purification. The present work shows that equally high labelling can be obtained with a variety of weak ligands and that the optimum quantity of stannous chloride is 2-4 micrograms. Although the label was stable to challenge with excess DTPA, cysteine was able to remove a portion of the label. We have also shown that this technique works with the IgG2a isotype in addition to the previously reported IgG1 isotype. This approach is simple, convenient and reproducible, and warrants further clinical evaluation.


A convenient method for regional monoamine oxidase-A determination by [14C]clorgyline autoradiography.

The availability of clorgyline for regional monoamine oxidase-A (MAO-A) determination was examined using [14C]clorgyline in rat. [14C]Clorgyline was synthesized by the methylation reaction of N-desmethyl-clorgyline and [14C]methyliodide in dimethylformamide with high radiochemical yield. The MAO-A distribution map by autoradiography correlated with that by histochemical technique and its quantity was consistent with the calculated MAO-A amount based on previous reports. The combination of labeled clorgyline and autoradiographic technique will promise the quantitative measurement of regional MAO-A distribution.


Tissue localization of [125I]triiodothyronine in the periorbital area of mice: a microautoradiographic study.

A significant retention of [125I]triiodothyronine ([125I]T3) in the retrobulbar orbital area of mice has been previously shown. The present study was initiated to determine tissue and intracellular localization of the thyroid hormone in the above area which is concerned in human Graves' disease of the thyroid. Male and female Balb C mice were intravenously injected with 0.1 mL of [125I]T3 (0.2 mCi/micrograms). At various time intervals (30 s-10 min) the animals were sacrificed, bled and periorbital tissues were isolated under a dissecting microscope. Three series of samples were prepared: (a) frozen samples for cryomicrotome sections, (b) samples fixed in 10% formaldehyde for paraffin embedded tissues and (c) samples fixed in paraformaldehyde (2%), glutaraldehyde (2%) and 0.1 M sodium cacodylate for embedding in Epon-Araldite-DDSA. Sections 5 microns and 400-600 A thick for light and electron microscopy, respectively, were coated with Ilford L4 emulsion and exposed for 9-21 days. Light microscope autoradiography demonstrated that [125I]T3 injected intravenously is rapidly transported in the cells of fat tissue of the peribulbar orbital area and tissues with glandular or muscular function: the hormone showed a high affinity for the intra- and extraorbital lacrymal gland cells, the cells of the Harder's gland, those of the sebaceous and meibomian glands of the eye-lids, as well as for local muscular structures. Electron microscope autoradiography showed that radioactivity is already localized inside the cells 30 s after the i.v. injection of [125I]T3 and it is distributed throughout the cytoplasm, with a higher concentration in the vesicles of the Harder's gland cells (rich in lipids and porphyrin), in the endoplasmic reticulum and the mitochondria of the lacrymal glands. 10 min after injection, a shifting of the radioactivity towards the nucleus area was observed. In conclusion, after in vivo injection, the thyroid hormone rapidly penetrates the cells of fat glandular and muscular tissues in the orbital area. Intracellularly, the affinity of the hormone for the secretory vesicles, rough endoplasmic reticulum, mitochondria and nucleus suggest that T3 could play a role in secretory and metabolic functions of the tissues in the retrobulbar orbital area.


Potential organ or tumor imaging agents. 32. A triglyceride ester of p-iodophenyl pentadecanoic acid as a potential hepatic imaging agent.

A triglyceride analog, glycerol-2-palmitoyl-1,3-di-15-(p-iodophenyl)pentadecanoate (DPPG) was synthesized and radiolabeled for evaluation as a potential functional liver scintigraphic agent. Uptake of DPPG was compared in normal, diabetic, tumor-bearing and heparin pretreated rats, revealing differences in uptake and clearance of radioactivity, correlating with hepatic lipase activity of these groups. Similar results were observed by gamma-camera scintigraphy. Comparing the uptake of DPPG with that of its fatty acid component, 15-(p-iodophenyl)pentadecanoic acid (IPPA), revealed that the peak uptake of IPPA in the liver was about half that of DPPG. Based upon these findings, DPPG warrants further study as a hepatic radiodiagnostic agent.


Internal-surface reversed-phase chromatography for plasma metabolite analysis of radiopharmaceuticals.

The use of internal-surface reversed-phase (ISRP) chromatography of unprocessed plasma samples was investigated as an alternative method of quantitation of the arterial plasma metabolite time course of [18F]N-methylspiperone. The ISRP method was directly compared to standard solid phase extraction/HPLC (SPE/HPLC) methods currently in wide use. Results indicate that: (1) the ISRP method is rapid and minimizes sample preparation; (2) recovery of radioactivity from the ISRP column is greater than 90%; (3) no radioactivity remains associated with chromatographically size excluded proteins and (4) the quantitative results are well correlated with conventional SPE/HPLC methods.


Tumor localization and radioimaging with mixtures of radioiodinated monoclonal antibodies directed to different colon cancer associated antigens.

After demonstrating enhanced tumor cell binding with a mixture of monoclonal antibodies (MAbs) in vitro, biodistribution and immunoscintigraphy studies with 3 radioiodinated anti-colon cancer MAbs and a non-specific control MAb (MOPC) were conducted in a human colon cancer (GW-39)-hamster model system. Each of the specific MAbs, but not MOPC, demonstrated extensive tumor binding and in scintigrams affected visualization of all large tumors (greater than 0.85 g) over background. Using single MAbs, few small tumors (0.19-0.50 g) were defined above background (0-29%). However, with combinations of these specific MAbs small tumors were more frequently defined in scintigrams (43-67%). Radioimages using higher doses of MAbs and small, younger tumors more clearly demonstrated the superiority of a MAb mixture. These results confirmed that combinations of MAbs to different antigens can detect smaller tumors with better tumor localization when compared to component MAbs used singly. This study supports the concept that tumor targeting and detection may be enhanced with appropriate mixtures of MAbs.


Labeling and stability of radiolabeled antibody fragments by a direct 99mTc-labeling method.

The in vitro labeling and stability of 99mTc-labeled antibody Fab' fragments prepared by a direct labeling technique were evaluated. Eight antibody fragments derived from murine IgG1 (N = 5), IgG2a (N = 2) and IgG3 (N = 1) isotypes were labeled with a preformed 99mTc-D-glucarate complex. No loss of radioactivity incorporation was observed for all the 99mTc-labeled antibody fragments after 24 h incubation at 37 degrees C. The 99mTc-labeled antibody fragments (IgG1, N = 2; IgG2a, N = 2; IgG3, N = 1) were stable upon challenge with DTPA, EDTA or acidic pH. Furthermore, using the affinity chromatography technique, two of the 99mTc-labeled antibody fragments displayed no loss of immunoreactivity after prolonged incubation in phosphate buffer up to 24 h at 37 degrees C. The bonding between 99mTc and antibody fragments was elucidated by challenging with a diamide ditholate (N2S2) compound. The Fab' with IgG2a isotype displayed tighter binding to 99mTc in comparison to the Fab' from IgG1 and IgG3 isotype in N2S2 challenge and incubation with human plasma. The in vivo biodistribution of five 99mTc-labeled fragments were evaluated in normal mice. In conclusion, the direct labeling method allows stable 99mTc labeling of antibody fragments from three of the major murine isotypes.


Synthesis and evaluation of technetium-99m monocationic mixed ligand complexes of phenyl substituted/condensed tetradentate Schiff's bases and trimethylphosphine.

Tc-99m monocationic mixed ligand complexes of phenyl substituted/condensed Schiff's bases, N,N'-ethylene-bis-(benzoylacetone imine) (Lb) or N,N'-ethylene-bis-(salicylaldehyde imine) (Lc) or N,N'-ethylene-bis-(2-hydroxyacetophenone imine) (Ld) and trimethylphosphine were synthesized to determine the influence of the presence of a phenyl group in these tracers on their heart uptake in rats. A new formulation procedure using aq. beta-hydroxypropylcyclodextrin (HPB) solution was developed for intravenous administration of nonpolar 99mTc complexes. Comparison of biodistribution data for the reference 99mTc complex from N,N'-ethylene-bis-(acetylacetone imine) and trimethylphosphine using HPB formulation and alternate formulation (0.9% saline) showed the same results. Biodistribution of the title 99mTc complexes, [99mTc Lb (PMe3)2]+, [99mTc Lc (PMe3)2]+ and [99mTc Ld (PMe3)2]+ showed heart-to-blood activity ratios of 1.7, 2.1 and 1.7, respectively, at 15 min post-injection in rats.


Design of compounds having enhanced tumour uptake, using serum albumin as a carrier--Part II. In vivo studies.

In the present in vivo study the uptake kinetics of radioiodinated albumin were determined in normal organs, and tumours of rats using sequential scintigraphy. Rat serum (RSA) was radioiodinated either directly at a tyrosine residue (d-RSA), or indirectly at a residualizing marker tagged to the albumin (rm-RSA). These labelling procedures did not alter the kinetics of labelled albumin, as shown by blood disappearance curves. Directly labelled albumin was shown to have tumour uptake. Residualizing markers like tyramine-cellobiose (TCB), tyramine-deoxysorbitol (TDS) and aminonaphthaltyrimide-deoxysorbitol (ANTDS) are metabolically inert. After the intracellular degradation of the albumin carrier the TCB-, TDS- and ATNDS-residues accumulate in the lysosomes, particularly those of tumour cells. It was able to be demonstrated that residualizing-marker tagged albumin-bound radioactivity was five times higher after 72 h than the tumour radioactivity after use of directly labelled RSA. These data found support when whole-body retention of directly labelled RSA, and residualizing marker-RSAs, were determined. After 72 h, 60% of 131I bound to RSA directly had been excreted, compared to only 25% of the activity attached indirectly to RSA with a residualizing marker. Whole-body autoradiography of rats injected with directly labelled RSA, or residualizing marker-RSA, support these results. Most of the radioactivity of directly labelled RSA was excreted within 24 h, whereas labelled residualizing marker-RSAs were also stored in tumour and liver tissue. ANTDS bound to RSA allows fluorescence microscopy. Cryosections of tumours from rats preinjected 10 min and 24 h with ANTDS-RSA before dissection, demonstrated that the fluorescence is localized on and in tumour cells. This indicates that cellular uptake of the marker takes place. Fluorescence was not observed in muscle tissue. This appears to suggest that the albumin uptake is greater in tumours than in normal tissue, and that it is metabolized in the tumour cells.


Subcellular distribution of tissue radiocopper following intravenous administration of 67Cu-labeled Cu-PTSM.

The subcellular distribution of radiocopper in the brain and liver of rats has been determined following i.v. administration of Cu-PTSM, pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II), labeled with copper-67. Homogenized tissue samples were separated by differential centrifugation into four subcellular fractions: (I) cell membrane + nuclei; (II) mitochondria; (III) microsomes; and (IV) cell cytosol. Upon sacrifice at 10 min post-Cu-PTSM injection, brain fractions, I, II, III and IV contain 35 +/- 12, 11 +/- 3, 2.8 +/- 1.3 and 51 +/- 7% of brain activity, respectively (n = 4). In animals sacrificed 24 h post-injection the subcellular fractions of brain tissue show little change from the radiocopper distribution seen at 10 min post-injection, although the mitochondrial fraction may contain slightly more tracer and the cytosolic fraction slightly less (I, 40 +/- 10%; II, 18 +/- 5%; III, 3.4 +/- 1.5%; and IV, 38 +/- 5%; n = 5). Subcellular fractions I, II, III and IV of liver contain 25 +/- 5, 12 +/- 3, 17 +/- 4 and 46 +/- 6% of 67Cu tracer in animals sacrificed 10 min post-Cu-PTSM injection. An identical subcellular distribution of 67Cu, was found in the liver following i.v. administration of ionic radiocopper (as Cu-citrate). The liver and brain cytosolic fractions at 10 min post-injection were further separated by Sephadex column chromatography. In liver cytosol, three different radiocopper components with molecular weights of about 140,000, 41,000-46,000 and 10,000-16,000 Da were found. In the brain supernatant fraction, most of the radiocopper was bound to a single low molecular weight cytosolic component (14,000-16,000 Da).(ABSTRACT TRUNCATED AT 250 WORDS)


A convenient synthesis of N-succinimidyl-3-iodo-[125I]benzoate, a reagent for protein iodination.

A convenient procedure has been developed for the synthesis of N-succinimidyl-3-iodo-[125I]benzoate. The procedure involved the synthesis of chloromercuribenzoic acid, its esterification with N-hydroxysuccinimide (NHS) and exchanging the mercury moiety with radioactive iodine in the presence of an oxidant. The obtained product was attached to human serum albumin and its stability was compared with Chloramine-T (Ch-T) radioiodinated protein. The results indicated that the reagent-radiolabeled protein was stable for longer periods and the deiodination rate was significantly lower.


Utility of technetium-t-butyl isonitrile (99mTc-TBI) myocardial imaging in coronary artery disease.

99mTc-t-butyl isonitrile is a useful agent for myocardial perfusion imaging. The superior physical advantages of technetium over 201thallium make larger doses possible for imaging. Accumulation in the myocardium is unidirectional in that once attached it does not leave the myocardium and hence two separate injections are needed for rest and stress imaging. High liver uptake frequently conceals the inferior wall and high early uptakes make immediate post-injection imaging almost impossible at least up to 45-60 min. This agent, however, was seen to accurately identify under-perfused areas and distinguish between ischaemia and infarct in our patients. Agreement with 201Tl and with GBP study of regional wall motion was excellent. While its individual sensitivity and specificity are quite high at 82.6 and 90.9%, in combined GBP studies the sensitivity rose to 93.4%. It is concluded that Tc-TBI is a valuable agent for myocardial perfusion scintigraphy, especially in a developing country like India where Tc-MIBI cannot be routinely used, since it is expensive, and where regular supplies of 201Tl are also not always feasible due to the high cost of importing. 99mTc-TBI can be made cheaply here and in a select population, notably in those with left anterior descending and circumflex coronary artery disease, it can provide valuable information.


Differences in mental task performance and slow potential shifts in subjects differing in cortisol level.

Hormones of the pituitary-adrenocortical axis (e.g., cortisol) are involved in the regulation of brain function. This study was aimed to clarify whether individual differences in baselines of cortisol are related to differences in heart rate (HR), slow brain potential shifts (SPS), performance data and personality. 17 males were instructed to solve 120 arithmetical tasks under time stress conditions. They could obtain monetary bonuses according to the accuracy of their task performance. This test condition was compared to a control condition. To determine the plasma level of cortisol by radioimmunoassays four blood samples were collected during the session. Baselines were estimated twice. A clustering procedure with respect to all cortisol levels resulted in a group of high responders (HC, n = 9) and a group of low responders (LC, n = 8). The HR was significantly higher in the HC group. The SPS of the LC group were characterized by a larger P300 elicited by the task followed by a steep negative slow wave (NSW) as compared to the HC group. LC subjects also showed a higher NSW before feedback presentation. The LC group solved the tasks faster and obtained more than twice the reward than the other group. They scored higher in achievement motivation and also reported increased 'Social Acceptance' and decreased 'Tiredness'. In sum, the results suggest a more efficient regulation of the arousal level of the LC group in contrast to the HC group as far as reflected in the parameters analysed.


Learning induces changes in the central cholinergic system of the rat in a sexually dimorphic pattern.

The involvement of the central cholinergic system in learning and the possible sexual dimorphism in related brain responses were investigated. Rats were exposed to different environmental conditions and to active avoidance learning. The resulting changes were studied using the following approaches: muscarinic receptor binding (MRB), acetylcholinesterase (AChE) and choline acetyltransferase (CAT) activities. The statistical evaluation of the data reveal that learning induces changes, especially in the postsynaptic component of the central cholinergic system, which shows some sexual dimorphism, and that males and females respond with different levels of increased cholinergic activity to informal and associative learning.


Effect of phenytoin on the human neuronal activity and depth event-related potential in emotional task.

Neuronal activity and depth ERP were recorded from cortical areas and subcortical nuclei of three patients with diagnostic and/or therapeutic intracerebral electrodes while they were performing emotional task before and after phenytoin administration. Phenytoin acted as a bioelectrical modulator, in some cases increasing and in some cases decreasing the mean background neuronal firing level. In some few cases the more specific task-related effect of phenytoin was found as an inversion of the inhibitory response into the excitatory one in trials evoking negative emotions.


Decrements in heart rate variability during memory search.

Heart-rate variability (HRV) was recorded from subjects as they rested or performed two memory-search tasks with different memory-set sizes. Results indicated that all the estimates of HRV were considerably greater during resting periods than during the task but only the mid-frequency band (0.1 Hz component) reflected the changes in memory-set size by a more pronounced decrement with the higher load. Subjective mental-effort ratings collected for the task periods also reflected the different memory loadings but did not correlate with HRV measures.


Effect of task decision on P300.

Previous studies have shown that the structure of an experimental task may modulate P300 (P3) responsiveness to task-related test stimuli. In this study, four tasks were compared to study possible effects of decision type on P3s to rare and frequent visual word stimuli. One or three oddballs were designated in two separate experiments. Subjects in each experiment viewed randomized and repeated presentations of nine 5- to 8-letter words, and performed each of four target detection and choice discrimination tasks: (1) silent counting of oddball(s), (2) button-press to oddball(s), (3) choice response ('yes' or 'no') to oddball(s) and frequents, and (4) choice button-press to oddball(s) and frequents. Although oddball stimuli elicited characteristic 'target' P3s over the parietal scalp, there was no significant effect of task type on the oddball-evoked P3. Frequents tended to elicit larger P3s in the choice discrimination tasks (yes/no, go/go) than in target-detection tasks (counting, go/no-go), indicating a selective effect of decision type on P3s to frequent-category events.


Computer determination of systolic time intervals based on impedance cardiography.

A computerized system has been developed based on impedance cardiography for processing systolic time intervals (STI) in psychophysiological experiments. The conventional method of STI determination is based on transducing three signals: electrocardiogram, phonocardiogram and pulse tracing (carotid pulse). Because of its negligible pulse transmission time the first derivative impedance cardiogram (dZ/dt) is more reliable than other pulse signals. Since the sharply demarcated points of the dZ/dt waveform occur simultaneously with the cardiac events the dZ/dt makes phonocardiogram processing unnecessary. Computer algorithms for STI assessment are based on processing two signals: the ECG and dZ/dt. The pre-ejection period (PEP), the left ventricular ejection time (LVET) and electromechanical systole (QS2) are derived by recognizing the B and X points on the dZ/dt signal as the endpoints of PEP and LVET respectively. X point identification consists of two steps: (i) the estimation of the QS2 based on the regression relationship between QS2 and heart rate (HR) and (ii) a filtering procedure for exact localization of the X point. The B point is determined by calculating the curvature function of the dZ/dt and employing a clustering procedure. The accuracy and reliability of the software were tested by processing data from 40 subjects under stress condition (cold pressor and mental arithmetic).


Rare events and the CNV--the oddball CNV.

Event-related brain potentials (ERPs), such as Nd and P300, change as a function of the proportion of time if a rare, significant, stimulus occurs. This 'oddball' paradigm has had a significant influence on the interpretation of ERPs in terms of the psychological and information-processing functions they reflect. Interpretations of transient components have differed considerably from that of the sustained potential known as the Contingent negative Variation (CNV), the latter appearing to reflect proactive rather than reactive brain processes. However, experiments in monkeys indicated that the CNV was also sensitive to the oddball effect. The purpose of this experiment was to replicate that finding in humans. The CNVs and P300s of five male and five female college students were studied under three conditions involving different proportions of two types of warning stimuli in a cued reaction time task (paired tone and light). The proportions of one of the warning stimuli, with respect to the total number of trials, were 0.10, 0.30 and 0.50. P300s were larger when elicited by rare warning tones only in the 0.10 condition with maximum P300 amplitude at the parietal site. CNVs at frontal and central areas were larger when the warning cue was the rare event, but there was no effect at the parietal site. These findings may require a rethinking of specific information processing interpretations of other endogenous ERPs, although the results also indicate that the 'oddball' effect on the P300 and CNV was distinctive in terms of scalp distributions and sensitivity to the manipulation.