Plasma neurotransmitter profile during different phases of the ovulatory cycle.

The influence of the different phases of the menstrual cycle on platelet-poor plasma norepinephrine (NE) and serotonin (5HT) was examined in 17 normal volunteers. The examinations were performed consecutively during 3 phases of the ovulatory cycle: 1) follicular phase, 2) ovulation, and 3) luteal phase. This investigation was initiated after a preliminary study in 51 volunteers showed wide and consistent variations of plasma NE and 5HT during the different phases of the cycle. Since in this first group the determinations had not been performed consecutively in the same subjects, and the changes observed in the different phases of the cycle could reflect interpersonal variations, the determinations were performed consecutively in a second group, concomitantly with serum estradiol (E2) and LH measurements. The results showed a decrease in plasma 5HT from the follicular phase [144.3 +/- 69.3 nmol/L (+/- SD)] to ovulation (55.7 +/- 41.4; P less than 0.001) and a subsequent increase in the luteal phase (141.3 +/- 96.4; P less than 0.01). The nadir in plasma 5HT showed an inverse correlation with serum LH (r = -0.07). Plasma NE increased from the follicular phase (1226.5 +/- 475.1 pmol/L) to ovulation (1694.0 +/- 564.4; P = 0.027) and reached a maximum in the luteal phase (2335.0 +/- 728.2; P = 0.0034). This rise correlated positively with serum E2. In conclusion, plasma 5HT and NE vary with the different phases of the menstrual cycle. Plasma NE rises during ovulation and seems to to correlate positively with serum E2 levels. Plasma 5HT reaches a nadir during ovulation and correlates inversely with serum LH.

Season of birth and autistic disorder in Israel.

OBJECTIVE: Variations in month of birth were examined in patients with infantile autism to test the hypothesis that birth in a particular month may be a risk factor for this disorder. METHOD: Data for autistic patients registered with the National League for Autism in Israel (N = 188) during the years 1964-1986 were compared with data on monthly distribution of live births in Israel for the corresponding period. RESULTS: After risk ratio estimates were computed for children born with infantile autism for each month, a significant increase was observed for children born in March and August. This association was true for each year throughout the study. An additional finding was a significantly higher rate of birth of autistic children in the years 1970-1976. CONCLUSIONS: This study, although made in a different climatic area than three earlier studies, further emphasizes the earlier findings that March and August births are a risk factor for development of autistic disorder.

Food preferences, body weight, and platelet-poor plasma serotonin and catecholamines.

The possible relationship between body weight, food preferences, and plasma neurotransmitters was investigated in 96 healthy volunteers. The volunteers were divided into groups according to sex, body mass index, and food preferences. In all groups fasting platelet-poor plasma (PPP) norepinephrine and serotonin (5-HT) were examined. PPP-5-HT was low in obese individuals (mean +/- SD: 51.7 +/- 34.6 nmol/L) in comparison with lean individuals (94.31 +/- 85.2 nmol/L; P < 0.01), in lean male carbohydrate cravers (22.7 +/- 16.4 nmol/L) in comparison with protein cravers (132.9 +/- 80.6 nmol/L; P < 0.005) and noncravers (64.7 +/- 51.7 nmol/L; P < 0.05), and in obese male carbohydrate cravers (34 +/- 22.7 nmol/L) in comparison with obese male protein cravers (98.8 +/- 28.4 nmol/L; P < 0.001). In conclusion, PPP-5-HT might be seen as a peripheral indicator of processes linked with food consumption and food preferences.

Early treatment of a single generalized tonic-clonic seizure to prevent recurrence.

BACKGROUND: The question of whether to start antiepileptic treatment after a single unprovoked seizure remains controversial and has been the subject of much debate in the relevant literature. OBJECTIVES: To determine the rate of recurrence of a second attack after a single unprovoked epileptic seizure by using 2 study groups of treated and untreated patients and, thus, to establish a treatment policy for these patients. PATIENTS AND METHODS: A group of 91 patients with a single generalized tonic-clonic seizure were prospectively studied; 87 of these patients completed the study. The end point of the study was 36 months after the single attack or the occurrence of a subsequent epileptic attack. The patients were randomly divided into 2 groups; 45 patients who immediately received anticonvulsive treatment and 42 who remained untreated for the follow-up period. Patients in the treated group were given monotherapy with carbamazepine. The results of recurrences were statistically analyzed by using the Kaplan-Meier method. RESULTS: Results indicated a significantly higher percentage of seizure-free patients in the treated group compared with that in the untreated group (P = .001). The treated men were proved to be less at risk for recurrent seizures compared with treated women (P < .001 vs P = .03, respectively). CONCLUSION: Treatment after a single unprovoked seizure leads to a significant reduction in the risk of relapse of generalized tonic-clonic epilepsy.

Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses.

We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned to receive a loading dose of immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years. The primary outcome measures were change in the yearly exacerbation rate (YER), proportion of exacerbation-free patients, and time until first exacerbation. Neurologic disability, exacerbation severity, and changes in brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion. Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate. Six patients in the IVIg group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group. The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group (p = 0.003). Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group. Total lesion score evaluated by brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups. Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS.

Prognostic significance of the initial electrocardiographic pattern in a first acute anterior wall myocardial infarction.

The availability of potent, but potentially dangerous, types of reperfusion therapy for acute myocardial infarction (AMI) has forced us to refine our tools for early and accurate diagnosis and for early risk stratification of patients with evolving AMI. The estimation of risk has to be made shortly after admission, when only the history, physical examination, and the ECG are available. This study was undertaken to compare in-hospital mortality with different patterns of the ECG obtained at admission in 147 consecutive patients with an evolving first AMI of the anterior wall. By using a new classification of the admission ECG, it was possible to divide the patients into 3 groups: (1) group A contained 12 patients with tall peaked T waves in the involved leads, without ST segment elevation; (2) group B comprised 77 patients with abnormal T waves and ST elevation, but without major changes in the terminal portion of the QRS complex; and (3) group C comprised 58 patients with abnormal T waves, ST elevation, and distortion of the terminal portion of the QRS. The mortality was 0, 3 percent, and 29 percent in groups A, B, and C, respectively (chi 2 = 22.91; p = 0). By using a logistic regression model, it was found that the initial ECG pattern alone is a strong predictor of in-hospital mortality in patients with an evolving anterior wall AMI. The predicted probabilities of death in groups A, B, and C are 0.0016, 0.025, and 0.29, respectively. This simple classification of the initial ECG pattern in patients with a first AMI of the anterior wall may enable the differentiation of patients with low in-hospital mortality (groups A and B) and of those with an in-hospital mortality of almost 30 percent (group C).

Prenatal ultrasonographic diagnosis of fetal heart echogenic foci: no correlation with Down syndrome.

OBJECTIVE: To determine whether karyotype is indicated when fetal heart echogenic foci are encountered on prenatal sonogram. METHODS: Pregnant women who presented at two large district hospitals in Israel that treat 7200 gravidas per year, and in whom fetal heart echogenic foci were diagnosed, were studied prospectively. Identified cases had detailed prenatal and postnatal echocardiographic examinations, and pregnancy outcome was assessed. RESULTS: During 18 months, 2214 low-risk pregnant women were examined sonographically, and 163 (7.4%) cases of fetal heart echogenic foci were detected at the first transvaginal sonography at 13-16 weeks' gestation. On a repeat scan at 20-22 weeks' gestation, 59.5% of the foci could not be identified, leaving only 66 (3%) cases for postnatal evaluation. Left ventricle-right ventricle ratio for location of the fetal heart echogenic foci was 3:1; 4.9% of all cases had bilateral findings. The karyotypes of 16 fetuses were normal and no additional abnormalities were found. The remaining 50 cases were normal in appearance at delivery without any features that suggested trisomy 21. A review of the English language literature revealed that six of 489 cases with fetal heart echogenic foci (1.2%) had trisomy 21. However, statistical analysis of a hypothetical sample that produced these six cases revealed that the calculated risk of trisomy 21 in a fetus with fetal heart echogenic foci is about 0.002%. CONCLUSION: Karyotyping is unwarranted in the mid-trimester fetus with incidental findings of fetal heart echogenic foci.

Cosmic rays activity and monthly number of deaths: a correlative study.

We studied the relation between the intensity of cosmic rays, the level of solar/geomagnetic activity, and the monthly numbers of deaths in a large hospital in Israel and in all Lithuania. The Israeli data include 30526 hospital deaths, two groups of fatal suicides (2359, 2763), and 15435 suicidal attempts for two periods of 108 and 236 consecutive months. The national data for the entire Republic of Lithuania include 424925 deaths for the period of 120 consecutive months. Cosmic rays intensity was measured by an Apatity neutron monitor. We obtained the data on solar, geomagnetic radiovawe propagation, ionosphere ionization hours, proton flux of two energy levels (>90 and 60 MeV) from the National Geophysical Data Center at Goddard Space Flight Center, National Space Environment Center at Boulder, Colorado, USA, and from the Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation (IZMIRAN), Russia. We calculated Pearson coefficients and their probabilities for correlation between monthly space activity level and monthly number of male and female deaths from different causes. Cosmic rays activity revealed significant negative correlation with solar/geomagnetic activity indices and related physical phenomena levels. This activity strongly correlated with flux of protons with the energies >90 MeV proton flux and did not exhibit significant correlation with 60 MeV proton fluxes. Cosmic rays intensity correlation with monthly numbers of deaths was strong for noncardiovascular deaths, suicides, and traffic accidents. The correlation was much weaker for deaths caused by ishemic heart disease and strokes.

Correlation of two levels of space proton flux with monthly distribution of deaths from cardiovascular disease and suicide.

In our previous studies /1-3/ we described some significant links between monthly number of deaths due to cardiovascular disease and suicide and space proton flux > 90 MeV. The aims of the present study were to compare the relationship of some solar and geomagnetic parameters with space proton fluxes of > 60 and > 90 MeV; to examine the monthly correlation of these two proton groups with the monthly death distribution in two countries, Israel and Lithuania. Physical data were obtained from the National Geophysical Data Center and the SESC in Boulder, CO; NSSDC in Goddard Space Flight Center, USA, and the Izmiran Institute of the Academy of Sciences in Russia. Pearson correlation coefficients and probabilities were compared for 56-180 consecutive months. Proton flux of > 60 MeV significantly correlated with three of the four studied monthly geomagnetic activity indices (Ap, Am, Dst), but not with such solar activity markers as sunspot number and solar flux (2800 MGH, 10.6 cm). There was no significant relationship between proton flux of > 60 MeV and monthly number of deaths from cardiovascular diseases and suicide, in contrast to the results for > 90 MeV. From the data available during the 36 months (1986-1988), there was no correlation between monthly levels of > 60 to > 90 MeV. In conclusion, a monthly space proton flux of > 60 MeV is not significantly correlated with the monthly death distribution from cardiovascular disease and suicide and some solar activity indices, such as proton flux of > 90 MeV. It is possible that the 60-90 MeV fraction in the > 60 MeV proton flux "blunts" the cosmobiological relationship between proton flux of > 90 MeV and monthly death number.

Israeli ED experience during the Gulf War.

The experience in an emergency department (ED) during the Gulf War in treating casualties referred to the ED soon after each missile attack is reported. Data were gathered within an 8-hour period of each nationwide alert on all patients who presented to the ED with injuries or complaints directly related to the missile attacks of the Tel Aviv area. One hundred three patients presented with symptoms directly related to the missile attacks. Of 103, 70 suffered from acute psychological reaction, 19 from false autoinjection of atropine, and nine from physical injuries from the explosion. Of the remainder, four had mild symptoms of smoke inhalation, and one had intercurrent myocardial infarction. The missile attacks resulted in a relatively small number of serious injuries. Most of the patients who presented to the ED soon after the missile attacks suffered from either anxiety reaction or false atropin injection.

Parental anxiety in febrile convulsions.

Febrile convulsions can cause extreme anxiety to parents. Factors associated with parental anxiety and its relief during and after admission of their child for simple febrile convulsions were studied by questionnaire. Of the 70 parents approached 46 responded (66%), all of whom reported feeling anxiety. Factors directly associated with parental anxiety were lack of knowledge regarding the management of seizures and the performance of a spinal tap or EEG. There was no correlation between a previous seizure in the same child or in a first-degree relative and a decrease in anxiety in the present seizure. Hospital admission of the child yielded no relief of anxiety in 27.3% and some relief in 34.1%. Staff activity was insufficient regarding parental instruction in handling the child in the event of a recurrence. About two-thirds of the parents wished to continue neurologic follow-up after discharge, and about one-half preferred that the child be treated with anticonvulsants. Our findings show that a very intensive effort is required to relieve parental anxiety after febrile convulsions. It is suggested that routine parental preventive education in this area be conducted in well-baby clinics.

One-year follow-up results of photorefractive keratectomy for low, moderate, and high primary astigmatism.

OBJECTIVE: To study the efficacy of excimer laser photorefractive keratectomy (PRK) for high, moderate, and low degrees of primary myopic astigmatism. PATIENTS AND METHODS: Ninety-two eyes of 54 patients with different degrees of compound myopic astigmatism underwent PRK. The eyes were divided by degree of refractive astigmatism into three groups-high (-2.75 to -5.0 diopters [D]), moderate (-1.25 to -2.50 D), and low (< or = 1.0 D). Refraction, corneal topography, slit-lamp findings, and visual acuity with and without correction were assessed. RESULTS: At 12 months, the mean reduction from the preoperative refractive cylinder was 80.7% in the high astigmatism group, 68.4% in the moderate astigmatism group, and 47.6% in the low astigmatism group. The post-treatment residual cylinder axis remained stable in 23 (38.3%) of 60 eyes and deviated in 37 (61.7%) of 60 eyes. The maximal deviation of the residual cylinder axis was 15 degrees. Of the 89.2% of eyes with low cylinder, 81.8% had moderate cylinder, and 85% of the eyes with high cylinder achieved a final uncorrected visual acuity between 20/20 and 20/35 at 12 months. CONCLUSIONS: A statistically significant reduction in the refractive cylinder was found in the high, moderate, and low astigmatism groups. The difference between the mean reduction of the high and moderate cylinders compared with the mean reduction of the low cylinders also was found to be statistically significant. The laser used in this study is an efficient tool for correcting high and moderate astigmatism. However, regarding low astigmatism, it was found to be less effective.

Neuropsychiatric assessment as a secondary outcome measure in a multiple sclerosis intravenous immunoglobulin L(IMg) trial.

Multiple sclerosis (MS) patients often suffer from abnormalities of mood including euphoria, depression, anxiety, pathological laughing and crying (PLC), and psychoses. We assessed neuropsychological functions (NF) as secondary outcome measures in relapsing-remitting multiple sclerosis (RRMS) patients treated by intravenous immunoglobulin (IVIg). Forty RR-MS patients (mean age 34.5±2.4; M : F=8: 32) were randomized to receive either IVIg or placebo in a double-blind trial for 2 years. NF evaluation at baseline, 1 and 2 years included the Goldberg Anxiety and Depression scales, the Brief Psychiatric Rating Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Mini-Mental State Examination. Baseline anxiety, depression and general psychopathology scores were similar for the IVIg and placebo groups. At 1 and 2 years, anxiety, depression and general psychopathology had decreased similarly in both groups compared with baseline. No significant cognitive changes were observed in either group. In the IVIg group PLC emerged in one patient and one patient developed clinically overt depression necessitating antidepressant treatment. In the placebo group, two patients developed a hypomanic episode, and PLC emerged in two patients. IVIg treatment is safe, according to psychiatric outcome measures, and these measures should be routinely used in RR-MS drug trials.

Relationship between immunoglobulin levels and extremes of solar activity.

The possible relationship between epidemics and extremes of solar activity has been discussed previously. The purpose of the present study was to verify whether differences in the levels of immunoglobulins (IgA, IgG, IgM) could be noted at the highest (July 1989) and lowest (September 1986) points of the last (21st) and present (22nd) 11-year solar cycle. The work was divided into a 1-month study (covering the month of minimal or maximal solar activity), a 3-month study (1 month before and after the month of minimal or maximal solar activity) and a 5-month study (2 months before and after the month of minimal or maximal solar activity). A trend of a drop-off for all three immunoglobulins was seen on the far side of the maximal point of the solar cycle. Statistical significance was achieved in the 5-month study for IgM (P = 0.04), and a strong trend was shown for IgG (P = 0.07). Differences between the sexes were also noted.

Recent trends in the epidemiology of Shigella species in Israel.

Trends in the epidemiology of infections due to Shigella species over a period of 6 years (1986-1991) in Israel were studied by analysis of the results of 51,300 stool cultures, of which 2,987 yielded Shigella species. In a university hospital, the relative prevalence of Shigella sonnei in patients with shigellosis increased over the years from 60% in 1986 to 91% in 1991 (r = 0.93; P = .007); concomitantly, the prevalence of Shigella flexneri decreased from 29% to only 8% (r = -0.80; P < .05). In the community, the increase in prevalence of S. sonnei was more moderate and occurred only from 1989 to 1991. Since 1990, S. sonnei has been isolated from more hospitalized patients than has S. flexneri, in contrast to their rates of isolation in the past. The increase in prevalence of S. sonnei was most prominent among children, in whom it caused 94% of shigella infections in 1991. Shigella boydii and Shigella dysenteriae remained relatively rare, causing approximately 5% and approximately 1%, respectively, of the cases of shigella infection. Concomitantly, the antimicrobial resistance of S. sonnei has become significantly greater, and it is currently 2.7 and 1.6 times higher than that of S. flexneri to trimethoprim-sulfamethoxazole and ampicillin, respectively. We conclude that the relative frequency of S. sonnei is increasing, especially in hospitalized patients, and hypothesize that this may be related to its increasing antimicrobial resistance. These trends have clinical implications.

The development of the fetal eye: in utero ultrasonographic measurements of the vitreous and lens.

Our objective was to establish nomograms for fetal eye measurements from 12 weeks' gestation by using transvaginal and transabdominal high-resolution ultrasound techniques. A prospective cross-sectional study was performed on 450 normal singleton pregnancies between 12 and 37 weeks' gestation. Vitreous and lens circumferences were measured by transvaginal ultrasonography until 17 weeks, and by abdominal ultrasound between 18 and 37 weeks' gestation. Regression analyses were used to create nomograms, and several transformations were done to obtain linearity. Eye measurements of 12 fetuses at risk for ocular disturbances were plotted on the constructed nomograms. Linear relationships were fitted between vitreous (r2 = 0.79) and lens (r2 = 0.88) circumferences and gestational age. In addition, there was a significant correlation between these measurements and the biparietal diameter. Data of the fetuses at risk showed that disturbances in ocular growth were associated mainly with abnormal cerebral development. These normative data may be helpful in the prenatal diagnosis of suspected congenital syndromes that include, among their manifestations, ocular growth disturbances such as microphthalmos and anophthalmos.

Development of the fetal tongue between 14 and 26 weeks of gestation: in utero ultrasonographic measurements.

Our objective was to establish nomograms for fetal tongue measurements from 14 weeks until mid-gestation by using transvaginal and transabdominal high-resolution ultrasound techniques. A prospective, cross-sectional study was performed on 120 normal singleton pregnancies between 14 and 26 weeks of gestation. Tongue circumference was measured by transvaginal ultrasonography between 14 and 17 weeks, and by abdominal ultrasound between 18 and 26 weeks of gestation. Fetal tongue circumference, as a function of gestational age, was expressed by the regression equation: tongue circumference (mm) = -23.9 + 3.75 x gestational age (weeks). The correlation, r2 = 0.95, was found to be highly statistically significant (p < 0.0001). The normal mean of tongue circumference per week and the 95% prediction limits were defined. During the study period we evaluated two cases with tongue circumference outside these 95% confidence limits: one had microglossia, the other macroglossia, and both were found to be associated with abnormal fetal karyotype. The presented normative data may be helpful in the prenatal diagnosis of suspected congenital syndromes that include, among their manifestations, tongue growth disturbances.

Compliance in hemodialysis patients: a multivariate regression analysis.

Successful treatment of patients with end-stage renal failure requires, in addition to dialysis, strict control of dietary, fluid and medication intake. In the present study we measured, in 50 chronic hemodialysis patients, serum potassium (K), serum phosphate (PO4) and interdialytic weight gain as indices of diet, medication and fluid compliance, respectively. Dietary compliance did not correlate with fluid or medication compliance, whereas fluid intake and medication compliance were related (p = 0.01). Age, time on dialysis, place of birth and whether the patient came accompanied or not to the dialysis unit were the main variables affecting serum K levels. Sex, ethnic origin and education significantly affected serum PO4. Sex, place of birth, marital status, number of children and years of education affected fluid intake. The compliance of the hemodialysis patient with different aspects of his regimen is thus multifactorial. Attempts to improve compliance and thus reduce morbidity and mortality should be aimed at identifying the population with low compliance and exposing them to educational programs.

Path analysis on the risk of mortality in very low birth weight infants.

OBJECTIVE: The purpose of this work is to clarify by path analysis which of the predictor factors of mortality in a cohort of 423 singletons VLBW infants born at Beilinson Medical Center during the years 1980-1990 (pre-surfactant era) exert direct or indirect effect on mortality. A direct risk factor was defined as a factor having an immediate effect on the outcome without working through an intermediate variable. By contrast, an indirect risk factor was defined as a factor that does not have a direct effect on the risk of mortality but instead works through an intermediate variable. Evaluation of mortality was done at three points over time (pre-delivery, at birth and post-delivery). RESULTS: In the pre-delivery model, gestational age, appropriateness for gestational age, mother's age and fetal distress work directly on mortality in VLBW infants. At birth, mother's age, birth weight and Apgar score at the fifth minute work directly on the risk of mortality. When the assessment of the risk of death was done post-delivery, mother's age, birth weight, Apgar score at the fifth minute and seizures influence directly on mortality risk, and fetal distress, gestational age and pre-natal induced hypertension (PIH) operate indirectly on the risk of mortality. CONCLUSION: The methodology we have used can be adopted in other investigations to distinguish and measure the effect of prognostic factors on the risk of an outcome.