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Biomedical subjects

J Sack

Publications and source records attributed to J Sack.

At least 37 records · Page 2Linked to original sources
PubMed1996

The problem of overlapping glaucoma families in the Glaucoma Inheritance Study in Tasmania (GIST).

The Glaucoma Inheritance Study in Tasmania (GIST) is a population survey of Australia's island state, Tasmania (population 450,000). Its aim is to find families with autosomal dominant, adult-onset, primary open angle glaucoma (POAG) suitable for genetic linkage analysis. POAG is relatively common, affecting around 3% of the Australian population. By finding the large families with POAG and identifying all the descendants in a captive population, it is possible that there may be overlap of different glaucoma pedigrees. Three of the first thirteen families in the study were composed of overlapping pedigrees. In one GIST family, GTas3, there has been intermarriage with other pedigrees with glaucoma on five occasions. The possibility of multiple genotypes was also reinforced by the inability to determine a single glaucoma phenotype in this family. When finding large families of POAG for linkage analysis, researchers must be aware of the risk of affected individuals inheriting their gene from the alternate parent. Thus, the alternate parents or their families must be examined, especially if the phenotype is atypical for the rest of the family.

Adult↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

A simple model for studying the correction of in utero hypothyroidism in the rat.

Although the placenta is only a limited barrier for the transfer of thyroxine (T4) to the fetus, we have recently demonstrated that maternal T4 does not suffice to prevent the effects of in utero hypothyroidism. The current study presents a convenient and minimally invasive animal model to study whether maternal-fetal transfer of T4 administered to the pregnant rat corrects the newborn's in utero hypothyroidism. In this model pregnant rats receive the goitrogen methimazole in their drinking water from d 10 of gestation until birth, either alone or together with L-T4. Circulating T4 levels in the dams and newborn pups are measured from blood spotted on filter paper by RIA. Using blood T4 levels as the measure, in the present study we found similar effects for orally and intraperitoneally administered T4. This rat model will allow future studies of whether maternal-fetal T4 transfer can correct the detrimental neurobehavioral effects of intrauterine hypothyroidism.

Administration, Oral↗
PubMed1993

Regulation of gastric H(+)-K(+)-ATPase by cAMP-dependent protein kinase.

A functional approach was utilized to isolate protein effectors from cAMP-stimulated rabbit gastric microsomes capable of stimulating H(+)-K(+)-ATPase activity. These studies have resulted in isolation of a cAMP-dependent protein kinase product from rabbit gastric microsomes which is capable of stimulating the proton pump of the parietal cell, H(+)-K(+)-ATPase, in inhibited gastric microsomes. This protein is membrane-bound and may be extracted from gastric microsomes only in the phosphorylated state. This phosphoprotein has at least 20 phosphorylation sites and produces enhancement of H(+)-K(+)-ATPase activity which equals that induced by the K+ ionophore, valinomycin. It would appear, therefore, that cAMP-mediated acid secretion involves phosphorylation of a membrane-bound cAMP-dependent protein kinase substrate in close proximity to the proton pump which produces K+ conductance and thereby controls the rate of acid secretion. The degree of phosphorylation of this protein is probably controlled by the activities of cAMP-dependent protein kinase and phosphoprotein phosphatase.

Adenosine Triphosphate↗
PubMed1993

Effect of short-term hyperthyroxinemia on vitamin D metabolism in congenital hypothyroidism.

The circulating concentrations of vitamin D metabolites were measured in nine children (four to ten years of age) with congenital hypothyroidism on L-thyroxine therapy, before and after a short term increase (33%) in dosage. The concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were not altered, but the concentration of 1,25 dihydroxyvitamin D was significantly higher in the serum of the children after three weeks of hyperthyroxinemia. This was associated with an increase in urinary calcium excretion. The increases in serum concentration of 1,25 dihydroxyvitamin D cannot be explained by differences in serum levels of calcium, phosphorus or parathyroid hormone. These findings differ from data obtained in adults.

25-Hydroxyvitamin D 2↗
PubMed1993

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↗
PubMed1993

Normative values for testicular descent from infancy to adulthood.

Measurements of testicular descent and volume were performed on 100 newborns and 144 older children and adults. Mean values of testicular descent were determined for age as well as for Tanner pubertal stage, establishing normative values. We later used these normative values for testicular descent to evaluate subjects who had undergone treatment for cryptorchidism many years previously. These normative values are useful both for the evaluation and follow-up of cryptorchid, suboptimally descended, and retractile testes, as well as for the evaluation and follow-up of therapy, and may prove especially useful in the decision for therapeutic intervention with suboptimally descended testes.

Adolescent↗
PubMed1993

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↗
PubMed1993

Body image of achondroplastic children before and after leg elongation.

Body image disturbance was studied in 6 achondroplastic children before and after surgical leg elongation (Wagner's procedure) using Fisher's Draw-a-Person Test and the Body Cathexis Test, as well as on another group of 6 achondroplastic children who had undergone the same procedure several years earlier. These groups were compared with 12 healthy control children. Gross disturbance of body image was present before the operation with a substantial improvement after the procedure. However, even years after the surgical procedure there still exists a difference in body image between the control-normal group and achondroplastic adolescents.

Achondroplasia↗
PubMed1992

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↗
PubMed1992

Endoscopic laser therapy for neoplastic lesions of the colorectum.

Surgical resection is the therapy of choice for most colorectal neoplasms. Endoscopic laser therapy (ELT) is a recently developed alternative for treatment of colorectal neoplasms and is applicable in a variety of clinical circumstances in which nonoperative treatment is preferable. The experience with ELT using the Nd:YAG (neodynium:yttrium-aluminum-garnet) laser in 42 patients was analyzed. The diagnosis was colorectal adenocarcinoma in 32 patients (76%) and neoplastic polyps in 10 (24%). ELT was undertaken either as a palliative treatment for malignant disease (60%), with curative intent for benign disease (26%), or as a temporizing measure (14%) in a total of 84 treatment sessions. Successful palliation or cure was achieved in 40 patients (95%) with 4 minor complications (9%) and no procedure-related deaths. This experience confirms ELT as an effective alternative to surgical therapy in the palliative, curative, or interim treatment of certain colorectal neoplasms in patients with prohibitive operative risk, limited anticipated survival, incurability, or diffidence toward operation.

Adenocarcinoma↗
PubMed1992

Isolation of a gastric phosphoprotein which stimulates acid secretion.

Stimulation of gastric acid secretion is mediated by cAMP which regulates the proton pump through an A-kinase-dependent phosphoprotein. The purpose of this study was to isolate a stimulation-dependent gastric phosphoprotein capable of stimulating acid secretion. Gastric glands were prepared from rabbit gastric mucosa and acid secretion was stimulated with cAMP. A detergent extract of these stimulated gastric membranes was fractionated by gel chromatography and assayed for functional activity by measurement of [14C]-aminopyrine accumulation in permeabilized resting gastric glands or measurement of H(+)-K(+)-ATPase activity in inhibited gastric microsomes. We hereby report isolation of a membrane-bound, A-kinase-dependent phosphoprotein which enhances aminopyrine accumulation in digitonin-permeabilized gastric glands (32%) and stimulates H(+)-K(+)-ATPase activity in gastric microsomes to a level 55% of the maximal stimulation observed in the presence of valinomycin. Incubation of this phosphoprotein with [32P]ATP and the catalytic subunit of A-kinase resulted in [32P] incorporation into a protein which coincided with a single protein band on SDS-PAGE (17,500 Da).

Animals↗