Calcium--an "all-round player" in the cornea.
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Calcium↗
Biomedical subjects
I Kaiserman
Publications and source records attributed to I Kaiserman.
Geographic variation in groundwater iodine and iodine deficiency in Israel, The West Bank and Gaza.
BACKGROUND: Iodine deficiency during pregnancy and infancy is the world's most common preventable cause of mental retardation. Previous studies have shown a high incidence of goiter and low groundwater iodine concentrations in northern Israel. OBJECTIVE: We examined the relationship between low groundwater iodine and iodine deficiency in pregnant women and schoolchildren. SUBJECTS AND METHODS: We measured the urinary iodine excretion of school-children in the West Bank and Gaza and rural and urban pregnant women in Western Galilee (an area known to have low groundwater iodine concentrations). We also measured iodine concentrations in groundwater in various locations in the West Bank and Gaza. RESULTS: Lower urinary iodine excretion was found among pregnant Arab women living in rural Western Galilee (101+/-7 microg iodine/g creatinine). 20% of them excreted <50 microg I/g creatinine. This is relatively less than found among pregnant Jewish women living in cities in the same area (154+/-13 microg I/g creatinine). Low iodine concentrations (<5 microg/l) were found in groundwater in the Nablus, Ramallah, Bethlehem highlands, as compared to normal concentrations in the lowland districts of the West Bank and Gaza. In a cohort of 728 schoolchildren aged 8-10, 10% (range 8-13%) of children from areas of low groundwater iodine had low levels of urinary iodine excretion, as compared to only <5% of those from districts with groundwater iodine concentrations >10 microg/l. CONCLUSIONS: Lower concentrations of groundwater iodine are related to low urinary iodine excretion in Israel, the West Bank and Gaza.
Child↗
Neuronal calcium sparks and intracellular calcium "noise".
Intracellular calcium ions are involved in many forms of cellular function. To accommodate so many control functions, a complex spatiotemporal organization of calcium signaling has developed. In both excitable and nonexcitable cells, calcium signaling was found to fluctuate. Sudden localized increases in the intracellular calcium concentration-or calcium sparks-were found in heart, striated and smooth muscle, Xenopus Laevis oocytes, and HeLa and P12 cells. In the nervous system, intracellular calcium ions were found important in key processes such as transmitter release, repetitive firing, and gene expression. Hence, we examined whether calcium sparks also exist in neurons. Using confocal laser-scanning microscopy and fluorescent probes, we found that calcium sparks exist in two types of neuronal preparations: the presynaptic boutons of the lizard neuromuscular junction and rat hippocampal neurons in cell culture. Control experiments exclude the possibility that these calcium sparks originate from instrumental or biological artifacts. Calcium sparks seem to be just the tip of the iceberg of a more general phenomenon of intracellular calcium "noise." We speculate that calcium sparks and calcium noise may be of key importance in calcium signaling in the nervous system.
Animals↗
Laser pointer maculopathy.
PURPOSE: To report a case of macular damage from a laser pointer. METHOD: Case report. A 19-year-old woman had an acute reduction of visual acuity in the right eye after deliberately staring into a commercial class 2 laser pointer for approximately 10 seconds. RESULTS: The patient's best-corrected visual acuity was RE: 20/40, and she had two small pericentral scotomata, as well as a hypopigmented ring-shaped lesion in the fovea. Within 8 weeks, her visual acuity improved to 20/20 and visual field returned to normal, but a subjective relative decrease in brightness of objects viewed by the right eye was apparent. Retinal pigment epithelial abnormality persisted. CONCLUSIONS: Commercial laser pointers, commonly used for teaching and entertainment purposes, may cause notable macular damage if abused. Morphologically, this may manifest as foveal retinal pigment epithelial disturbance.
Acute Disease↗
Ion channels in presynaptic nerve terminals and control of transmitter release.
The primary function of the presynaptic nerve terminal is to release transmitter quanta and thus activate the postsynaptic target cell. In almost every step leading to the release of transmitter quanta, there is a substantial involvement of ion channels. In this review, the multitude of ion channels in the presynaptic terminal are surveyed. There are at least 12 different major categories of ion channels representing several tens of different ion channel types; the number of different ion channel molecules at presynaptic nerve terminals is many hundreds. We describe the different ion channel molecules at the surface membrane and inside the nerve terminal in the context of their possible role in the process of transmitter release. Frequently, a number of different ion channel molecules, with the same basic function, are present at the same nerve terminal. This is especially evident in the cases of calcium channels and potassium channels. This abundance of ion channels allows for a physiological and pharmacological fine tuning of the process of transmitter release and thus of synaptic transmission.
Animals↗
Effect of aspirin intake on bleeding during cataract surgery.
PURPOSE: To study the association between chronic intake of aspirin and intraoperative bleeding during cataract surgery and the effect of discontinuing the medication before surgery. SETTING: Department of Ophthalmology, Meir Hospital, Sapir Medical Center, Kfar-Saba, Israel. METHODS: Sixty-one patients having cataract surgery and receiving aspirin to prevent thromboembolic events were divided into 3 groups: Group A, continuation of the medication; Group B, cessation of aspirin intake for 2 to 5 days before surgery; Group C, cessation of medication for 7 to 10 days before surgery. Blood tests of coagulation parameters, a detailed questionnaire, and 1 day and 1 week follow-up were evaluated. RESULTS: There were no significant differences in blood tests and the amount and incidence of intraoperative bleeding among the 3 groups. Diathermy was used somewhat more in Group A; however, there was no difficulty stopping the bleeding in any case and discontinuation of the medication had no effect on the intraoperative course or postoperative outcome. CONCLUSIONS: Aspirin intake was not associated with significant intraoperative bleeding; thus, discontinuation of aspirin is usually not indicated. Clear corneal phacoemulsification is advantageous in patients receiving antiplatelet therapy.
Aspirin↗
Congenital hypothyroidism screening in the West Bank: a test case for screening in developing regions.
Screening for congenital hypothyroidism (CH) among the Arab population of the West Bank began in May 1987 as part of the neonatal screening program in Israel. In the West Bank many infants are born at home or are released from the hospital on the 1st day after birth and thus cannot be screened. However, we tried to reach the infants before the age of 1 month at the maternal and child health centers, where they receive immunization. In this screening program, 64% of the infants were sampled by the 1st week and 93% by 3 weeks of life. In contrast to the screening in Israel, where thyroxine determination is followed by thyroid-stimulating hormone measurement, in the West Bank thyroid-stimulating hormone was tested first in order to decrease the recall rates. From June 1990 to February 1994, 49,694 infants were screened in the West Bank, of whom 24 with CH were detected (an incidence of 1:2,070). From January 1987 to February 1994, 28,938 infants were screened in East Jerusalem, of whom 20 with CH were detected (incidence 1:1,447). There were differences between the incidence rates in the various districts. The incidence rates were higher than those reported from industrialized countries, but similar to those found in Saudi Arabia. This may be due to the high degree of consanguineous marriages among Arab populations and to environmental factors. In conclusion, in spite of the many difficulties, both practical and political, CH screening in the West Bank is feasible. Although screening all newborns shortly after birth is not possible, this study shows that a high percentage of them can be screened at a time when they can still be effectively treated. Our results could be used in due time as a baseline for a future independent screening program.
Age Distribution↗
21-Hydroxylase deficiency: screening and incidence in Israel.
BACKGROUND: Neonatal screening for congenital adrenal hyperplasia was introduced in 1977. However, even today only a few national screening programs exist and their cost effectiveness is still debatable. This study was conducted in order to evaluate the advisability of a national or regional screening program in Israel. METHODS: From June 1987 until December 1992 we screened a countrywide random sample of 113,846 newborns for 21-hydroxylase (21-OH) deficiency measuring 17alpha-OH progesterone (17-OHP) from blood spotted on filter paper. Between January 1993 and August 1995 we continued the screening program concentrating on the population of northern Israel. A total of 56,958 newborns were screened. We compared these findings with the incidence of 21-OH deficiency in the total population born in Israel during the years 1986-1991. RESULTS: In the countrywide screening program, 4 newborns (2 Arabs and 2 Jews) were found to have levels of 17-OHP between 409 and 2,049 nmol/l (2 males and 2 females). This constitutes a low incidence of 1 in 28,462 live births. In the north-Israel screening program 4 newborns (all Arabs) were detected (2 males and 2 females) constituting a much higher incidence of 1 in 14,240 live births. The data obtained from the archives revealed that the incidence of 21-OH deficiency nationwide during the years 1986-1991 was 1:19,000 live births, 1:30,000 for Jews and 1:8,000 for Arabs. The incidence of 21-OH deficiency among Arab newborns in the northern part of the country was as high as 1:5,000 (14:71,130). The female to male (F:M) ratio was 2.6:1 and the ratio of the salt-losing to the simple virilizing variant was 5:1. Two male patients were diagnosed prenatally, 21 patients (17 F and 4 M) during the first month after birth and 6 others subsequently. CONCLUSIONS: The high F:M ratio of 21-OH deficiency in the total population compared to a 1:1 ratio in our random screening programs suggests that 21-OH-deficient male patients in the general population might have been missed or died early due to a salt-losing crisis. The high incidence of this disease in the northern part of the country and especially among the Arabs, suggests that screening in this part of the country, especially among the Arab population, is warranted and might save the lives of some male patients.
Adrenal Hyperplasia, Congenital↗
Cross genotype sex hormone treatment in two cases of hypogonadal osteoporosis.
BACKGROUND: Sex hormone deficiency is the most common cause of bone loss. Reduced bone mass and an increased risk for osteoporotic fractures have been described in hypogonadal subjects of both sexes. We present here the results of treating two patients showing abnormal sexual differentiation (an XX male and an XY female), who suffered from bone loss related to sex hormone deficiency, with cross genotype sex hormones. SUBJECTS AND METHODS: Patient 1 was an asymptomatic 39-yr-old XY female with complete androgen insensitivity. Her testes had been removed, and she later discontinued estrogen treatment. Patient 2, a 37-yr-old XX male, had congenital adrenal hyperplasia, which led to a masculine phenotype. He was ovariectomized and reared as a male. He was treated with glucocorticoids but refused androgen treatment for many years. We treated both patients with phenotypically matched sex hormones (patient 1 received conjugated estrogens 1.25 mg/day, and patient 2 received 250 mg testosterone every 4 weeks) and followed their bone mineral density (BMD) using dual-energy X-ray absorptiometry, urine calcium, and hydroxyproline excretion. RESULTS: Before treatment both patients had low sex hormones and highly elevated gonadotropins. As a result of treatment urine hydroxyproline excretion decreased from 45 and 26.7 mg/g creatinine to 15 and 15.9 mg/g creatinine in patients 1 and 2 respectively. In patient 1, lumbar BMD rose from 0.912gr/cm2 to 0.976gr/cm2 and femoral neck BMD rose from 0.716gr/cm2 to 0.836gr/cm2 after 4 years of treatment. In patient 2, lumbar BMD rose from 0.717gr/cm2 to 0.815gr/cm2 and the femoral neck BMD rose from 0.509gr/cm2 to 0.635gr/cm2 after 27 months of treatment. CONCLUSIONS: Phenotypically-matched sex hormone therapy in patients with abnormal sexual differentiation is essential not only to maintain external appearance but also for the preservation of bone mass.
Adult↗
Effects of immigration on the incidence of congenital hypothyroidism.
OBJECTIVE: The incidence of congenital hypothyroidism (CH) has been shown to vary among different parts of the world. This could result from environmental or hereditary factors. Studies of other congenital diseases have shown that immigrants tend to retain the incidence of their country of origin while their children acquire the incidence of their new homeland, suggesting an environmental influence. This study aimed to assess the differences in the incidence of CH among immigrants from different parts of the world and to study the effects of immigration on its occurrence. METHODS: During the 9-year period between 1979 and 1987, 196 Jewish infants with primary CH were born in Israel; this constitutes an incidence of 1:3354 live births. We collected data from hospitals, endocrine pediatric clinics and the children's parents regarding the birth place of the parents and grandparents of those infants. These data were compared with the birth place of the parents and grandparents of all infants born in Israel during that period in order to learn about the incidence of CH among infants of different origins and to compare the incidence between children of parents born in Israel and those of immigrants of the same grandparental origin. RESULTS: CH incidence was lower among offspring of mothers and fathers of Israeli origin (1:4717 and 1:4255 live births respectively) and higher among those of African mothers (1:2950) and Asian fathers (1:2941). Parents of Asian or African origin, born in Israel have a lower incidence of CH-affected children compared with parents of the same origin born in their own continent. This trend is reversed for European and American parents, for whom being born in Israel is related to an increase in the CH incidence in their children. The difference in CH incidence between offspring of parents born in Israel and those of parents born in their original country was statistically significant (P < 0.05). In the different origin groups the gender of the parent did not influence significantly the incidence of CH. CONCLUSIONS: Environmental changes resulting from immigration can influence the incidence of congenital hypothyroidism.
Adult↗
Regional and temporal fluctuations in the incidence of congenital hypothyroidism in Israel.
It is well known that the incidence of congenital hypothyroidism (CH) differs significantly among different parts of the world. Northern Israel has been shown to be an iodine deficient area with a relatively high incidence of CH. This study aimed to compare the incidence of CH between different regions of Israel and to examine the temporal fluctuations of this disease in each region. All 303 primary CH infants born in Israel during the 10-year period between April 1978 and March 1988 were classified by hospital of birth and place of residence. Using these data we calculated the incidence of CH in the different subdistricts and districts of Israel. We also calculated the annual incidence of CH in each district. The incidence of CH in each hospital was compared to the filter paper T4 levels of all newborns born in that hospital during 1993. The incidence of CH decreased gradually from northern to southern Israel. This trend was also observed for thyroid agenesis, but the incidence of ectopic thyroid was highest in central Israel. Dyshormonogenesis (DHG) was on average 3.5 fold more frequent in the Arab compared to the Jewish populations, but did not show any clear geographic pattern. A significantly increased CH incidence in north-central Israel in 1985 was opposed by a low incidence in the South. A clear correlation exists between the incidence of CH in each hospital and the mean newborns' T4 level in that hospital. The incidence of primary CH in general, and of thyroid agenesis and ectopic thyroid specifically, has a clear regional-temporal pattern. Thus, some of the factors causing CH in Israel may be local factors that show local annual fluctuations.
Analysis of Variance↗
The importance of thyroglobulin levels in monitoring the treatment of congenital hypothyroidism.
We have previously reported on high thyroid-stimulating hormone (TSH) concentrations in clinically euthyroid children with congenital hypothyroidism (CH) undergoing appropriate treatment. Whether this TSH is biologically active or not is still unclear. It has been shown that ectopic thyroid tissue does not involute during thyroxine (T4) therapy and thus can continue to secrete thyroglobulin (Tg). This study was undertaken to determine whether the Tg levels in ectopic CH infants represent residual thyroid tissue stimulated by biologically active TSH and whether this Tg can be used to help monitor CH treatment. Among the 51 primary CH children (age 2-14 years) diagnosed and followed up by us, 28 had measurable Tg values (> 2 pmol/l) several years after the T4 treatment had been started. In 8 of the children, Tg was measured as early as the time of diagnosis and followed up for at least 3 years. The Tg levels decreased much more slowly than the TSH levels did, and secondary Tg rises were observed. By 5 months of age, all children had Tg levels less than 25 pmol/l. Although in some infants the Tg levels paralleled TSH behavior, in others the TSH-Tg correlation was not so obvious. In another group of 8 children who had high TSH values despite normal T4, the LT4 replacement dosage was increased by 60% for 1 week (from 3.5 +/- 0.2 to 5.5 +/- 0.5 micrograms/kg/day) in order to examine the TSH-Tg dependence.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Kinetics of the pituitary-thyroid axis and the peripheral thyroid hormones in 2 children with thyroxine intoxication.
Thyroxine intoxication is a benign, nonfatal condition, relatively common in the pediatric age group. We present here a detailed laboratory follow-up of all thyroidal hormones in 2 healthy girls who inadvertently ingested 2,500 micrograms of L-thyroxine. The two girls were hospitalized and treated with ipecac, gastric lavage, propranolol, prednisone, cholestyramin and propyl-thiouracil. All physical signs were normal and no symptoms were reported. All thyroidal hormones were measured 12 times from 2 h to 20 days after the ingestion. For T4, T3, rT3 and thyroglobulin (Tg) a one-compartment kinetic model was formulated and fitted to the empirical data. The kinetic data constants of production and elimination were calculated, as well as the metabolic clearance rate. All laboratory values were similar in both girls. T4 serum levels were already high 2 h after the intoxication and returned to normal values only after 13 days. Fitting the T4 serum levels with a one-compartment model resulted in absorption and degradation constants similar to those in normal adult subjects. Thyroid-stimulating hormone (TSH) levels decreased reaching their lowest concentration 14 h after the intoxication. They remained low till the 4th day, after which they rose gradually. Twenty days after the intoxication, TSH levels were still below their initial values. T3 reached its peak levels 11 h after the ingestion and decreased to normal values after 3 days. Both T3 production constants and T3 degradation constants were significantly increased. rT3 reached its peak level on the 2nd day after the intoxication and decreased to normal values on the 4th day. Its production and degradation constants were somewhat below normal levels. The T3/rT3 ratio decreased from a normal level of around 3 to as low as 1 and rose again after 13 days to extremely high levels (as high as 8). Tg serum levels dropped continuously with a half-life of 1-5 days and started rising again after 2-13 days. In conclusion, T4 intoxication in the child is combated primarily by a significant increase in T3 production and degradation, while meticulously maintaining relatively low T3 levels.
Child, Preschool↗
Home monitoring of 17 alpha-hydroxyprogesterone levels by filter paper blood spots in patients with 21-hydroxylase deficiency.
BACKGROUND: 21-Hydroxylase (21-OH) deficiency is characterized by an excess of androgen in both sexes and premature skeletal maturation resulting in short adult stature and male infertility. To achieve optimal height in children and fertility in adults, the replacement treatment of 21-OH deficiency with glucocorticoids should be regulated in order to adequately reduce the excess of androgens while minimizing the dose of glucocorticoids required. Neonatal screening for 21-OH deficiency is based on the measurement of the 17 alpha-hydroxyprogesterone (17-OHP) level from blood spotted on filter paper. The aim of this study was to examine whether repeated daily blood sampling on filter paper can assist in improving the monitoring of, and compliance to, 21-OH deficiency treatment. METHODS: During a 5-year period (1989-1994) we instructed 8 patients with 21-OH deficiency (2 males with salt losing, 2 males and 1 female simple virilizing, and 1 male and 2 females with nonclassical 21-OH deficiency) aged 1.3-36 years to sample blood on filter papers 1-4 times a day and send the papers to our neonatal screening laboratory by mail. On 62 occasions we measured both serum and filter paper 17-OHP levels in order to assess the degree of correlation between the two methods. RESULTS: Comparison between the filter paper and serum 17-OHP levels showed a correlation coefficient of r = 0.87. The filter paper levels were almost always higher than the serum levels. The serum 17-OHP levels were < 1 ng/ml whenever the filter paper levels were < 3 ng/ml. On long-term follow-up of 17-OHP filter paper levels we observed major diurnal and day-to-day fluctuations which might not have been noticed on routine follow-up clinic visits. CONCLUSIONS: Filter paper follow-up of 17-OHP levels can assist in optimizing the replacement treatment in patients with 21-OH deficiency while reinforcing compliance and decreasing the need for frequent clinic visits and hospitalizations. By adjusting the glucocorticoid type, dose, and time of administration to each patient we should be able to achieve optimal growth without bone age acceleration in children, to avoid overtreatment, and to improve fertility in adults.
17-alpha-Hydroxyprogesterone↗
Maternal-fetal T4 transfer does not suffice to prevent the effects of in utero hypothyroidism.
It has been suggested recently that in congenitally hypothyroid infants with organification defect there is a maternal-fetal transfer of thyroxine (T4). The present study was conducted to evaluate how effective the maternal-fetal transfer is and whether the maternal T4 can prevent intrauterine hypothyroidism. The clinical, laboratory and radiological data on 271 full-term infants with persistent primary congenital hypothyroidism, detected by the national screening program, were used to assess the degree of in utero hypothyroidism. For 6 out of 50 athyroid infants, two pretreatment blood samples spotted on filter paper were available for calculating the T4 disappearance rate. Most infants with agenesis of the thyroid had very low T4 and very high levels of thyroid-stimulating hormone compared to infants with ectopic thyroid. In the athyroid infants the initial T4 declined to low and undetectable levels. Bone maturation was significantly delayed while the clinical symptomatology was more prominent in the athyroid congenital hypothyroid infants, as compared with the ectopic thyroid infants. In conclusion, there is some maternal-fetal transfer of T4. However, this transfer is insufficient to suppress the fetal levels of thyroid-stimulating hormone and prevent intrauterine hypothyroidism.
Bone Development↗
Early identification of congenital hypothyroid infants with abnormalities in pituitary setpoint for T4-induced TSH release.
It is now clear that early detection and adequate replacement therapy of congenital hypothyroidism (CH) results in normal growth and psychomotor development. However, there is evidence that some of those infants might have a persistent alteration in the T4 feedback control of TSH release. To characterize further this phenomenon, 25 treated CH children were divided into two groups: group A consisted of children whose TSH was suppressed as early as 1 month after the onset of therapy, and group B consisted of children whose TSH suppression occurred much later. There were no differences in the etiology of CH, in the mean T4 and T3 serum levels or in the mean LT4 treatment dosage between the two groups. All children were clinically euthyroid throughout the follow-up, developed according to expected norms and no deviations were noted in bone age. However, serum TSH levels remained elevated in group B infants throughout the follow-up period (up to 14 years). Increase of LT4 treatment dosage resulted in TSH suppression in both groups. However, the TSH levels obtained in group B were still higher compared to group A. These results suggest that some CH infants might have an abnormal setpoint for T4 control of TSH secretion and that these infants can be detected as early as 1 month after birth. Thus, serum T4, T3 levels and clinical progress are better guides to the adequacy of therapy than serum TSH concentrations in this group of CH infants.
Adolescent↗
Congenital anomalies concomitant with persistent primary congenital hypothyroidism.
The Israeli national neonatal screening program for congenital hypothyroidism (CH) was initiated in May 1978. The overall incidence of persistent primary congenital hypothyroidism (PPCH) during the first 10 years of screening was 1:2,950 live births. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with PPCH and to compare it with the Israeli Birth Defect Monitoring System data. Among 243 PPCH infants on whom adequate data were available, 38 infants (15.6%) had associated congenital anomalies. Fourteen infants had congenital cardiac anomalies (5.8%): VSD (n = 7), PDA (n = 3), PS (n = 2), one mitral insufficiency, and one congenital atrial flutter. Eight children (3.3%) had congenital dislocation of the hip; their M:F ratio was 3:5 similar to the M:F ratio in CH (unlike the ratio in the general population). Some additional anomalies were considerably more common than in the general population. It is reasonable to assume that teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETA.
Congenital Abnormalities↗
A ten-year temporal analysis of primary congenital hypothyroidism in Israel.
It was previously shown that some congenital malformations present seasonal variations, suggesting a seasonal etiology such as viral infections. Some earlier studies have shown a certain degree of variation in the incidence rates of congenital hypothyroidism. As from April 1978 all infants born in Israel were screened for congenital hypothyroidism (CH) in one central laboratory at the Sheba Medical Center Tel-Hashomer. During the 10-year screening period (April 1978 to March 1988) 303 infants were found to have primary CH, which constitutes an overall incidence of 1/3192 live births. The annual and monthly birth incidence was calculated for the 120 months of the screening period. The annual CH incidence was significantly low in 1978 and 1979 and significantly high in 1985. There were wide and significant variations in the individual monthly incidences of CH. The average monthly incidence showed a low peak in August; however the autocorrelation analysis of the monthly incidences of CH showed no significant periodicity. This was supported by the Fourier analysis which showed no distinctive frequency peak. The last menstrual period was calculated for 138 of the infants' mothers and an autocorrelation analysis of these dates showed no significant periodicity. These results support a non-periodic etiology for sporadic primary CH in Israel.
Congenital Hypothyroidism↗