Harry Hirsch - Academia.edu (original) (raw)

Papers by Harry Hirsch

The Journal of Pediatrics, 2009

PubMed, 1980

Studies were performed on anesthetized dogs to determine the relationship between endotoxin-induc... more Studies were performed on anesthetized dogs to determine the relationship between endotoxin-induced alterations in pancreatic blood flow (PBF) and hormones that originate partially or completely from the pancreas. PBF was estimated in six dogs by radioactive microspheres (praeendoxin, 25 and 240 minutes postendotoxin). Insulin, glucagon, pancreatic polypeptide (PP), and somatostatin-like immunoreactivity (SLI) were assayed in arterial and portal venous blood. Cardiac output and mean arterial blood pressure (MABP) decreased 25 minutes after endotoxin administration (50% and 40%, respectively) and returned toward normal levels by four hours. However, there was 74% decrease in PBF at 25 minutes and a further drop four hours after endotoxin. Hormonal responses were characterized by a short-lived increase in arterial insulin, corresponding to a transient increase in blood glucose. Insulin release increased shortly after endotoxin. Arterial glucagon and PP increased two to five hours after endotoxin. There was a suggestion that the increase in PP was of nonpancreatic origin. Little change in plasma SLI was noted following endotoxin. Thus, it appears that endotoxin altered the release of different pancreatic hormones with a variable time courses.

Nephron Clinical Practice, 1989

Biochimica Et Biophysica Acta - Proteins And Proteomics, Oct 1, 1972

Abstract A comparison of the t 1 2 of in vivo and in vitro labeled rat high density lipoprotein s... more Abstract A comparison of the t 1 2 of in vivo and in vitro labeled rat high density lipoprotein showed that they behave metabolically alike. It was shown that labeling of high density lipoprotein with 125I in vitro, and with [14C leucine in vivo, results in a similar distribution of label among the subunits of the apolipoprotein. The rates of degradation of the various subunits of high density lipoprotein of rats were studied. After injection of radioiodinated high density lipoprotein, the distribution of radioactivity in the subunits of high density lipoprotein was determined; it was found to be unchanged between 1 and 48 h after injection. This indicates that the various subunits of high density lipoprotein have similar rates of removal. When the t 1 2 of these subunits was measured, a rather similar half life of 8.5–11.5 h was found. A fast and a slow component were shown to be present in the turnover curve of in vivo labeled very low density lipoprotein. The fast component had a t 1 2 less than 1 h while the slow component had a t 1 2 of 10–12 h. After injection of radioiodinated high density lipoprotein, radioactivity appeared in some of the subunits of very low density lipoprotein. Assuming a common pool for these subunits of very low and high density lipoproteins, these data would suggest that these very low density lipoprotein subunits have a slower rate of removal than the other subunits of very low density lipoprotein.

European Journal of Pediatrics, Aug 1, 1988

We diagnosed isolated gonadotropin deficiency in a 17-year-old boy with orbital hypotelorism and ... more We diagnosed isolated gonadotropin deficiency in a 17-year-old boy with orbital hypotelorism and median cleft lip and palate.

Journal of Endocrinological Investigation, Oct 1, 1984

Thyroid function has been evaluated in 6 prepubertal male and 9 female thalassemic patients. Four... more Thyroid function has been evaluated in 6 prepubertal male and 9 female thalassemic patients. Four of the latter were sexually immature (Group I), with very low estradiol levels and the remainder had more advanced sexual development (Group II). Subjects were challenged with TRH and the response compared to adult controls and a group of 15 males aged 13-18 years with constitutional delayed adolescence. All patient groups and controls had normal levels of T4, T3 and T3 resin uptake. When compared to adult controls or males with constitutional delayed adolescence, the male thalassemic patients had increased basal TSH levels with an exaggerated response to TRH. Long term testosterone enanthate led to a decrease in integrated TSH secretion, showing that androgens may decrease the TSH response to TRH. The more sexually mature females of Group II also had increased basal and stimulated TSH levels; however, the sexually immature females of Group I had basal TSH and TSH responses to TRH equivalent to female controls. In Group I patients there were, moreover, no changes in TSH response during administration of estradiol valearate for 3 months and conjugated estrogens for 8 months. The high basal and stimulated TSH levels in the males and Group II females are most likely due to subclinical primary hypothyroidism. This has been previously described in thalassemia. On the other hand, failure of estrogens to increase the TSH response to TRH in Group I females is evidence of pituitary involvement, which is also well documented in this clinical condition.(ABSTRACT TRUNCATED AT 250 WORDS)

American Journal of Medical Genetics, Jul 5, 2023

Current published guidelines for routine care of women with Prader–Willi syndrome (PWS) do not in... more Current published guidelines for routine care of women with Prader–Willi syndrome (PWS) do not include recommendations for gynecologic examinations. We describe our experience with gynecological examinations in women with PWS and offer recommendations for routine health care for these patients. Data were collected on all 41 PWS females ages ≥12 year, followed in our national Israeli multidisciplinary clinic between the years 2011 and 2022. Menstrual data and findings on external gynecological examination, including evaluation of the vulva and hymen were recorded at yearly visits. During the gynecological evaluation the topic of sexual education was discussed. Pelvic ultrasound, specifically for antral follicular count, was performed for those visiting the clinic during 2020–2022. Blood samples for luteinizing hormone (LH), follicular stimulating hormone (FSH), and estradiol were obtained routinely and DEXA scans for bone density were done when indicated. Of the 41 women, (median age at start of follow‐up 17 years, range [12.3–39], BMI 30.4 kg/m2 [IQR 23.5–37.1]), 39 women agreed to external gynecological examination. Eleven women (27%) had spontaneous menses, with menarche at the age of 14 to as late as 31 years. The hymen was intact in all except one. Poor hygiene was observed in eight women, three women with vulvovaginitis, and five with irritated vulva related to poor hygiene. Gynecological ultrasound was performed in 27 women. In 22, endometrial thickness was less than 5 mm. The median antral follicular count (AFC) was 6 (<10th percentile for age). No correlation between AFC and menstruation or BMI was found. Mean FSH level was 5.7 ± 3.6 IU, LH was 2.29 ± 2.23, and estradiol was 128 ± 76 pmol/L. Data on DEXA measurements were available in 25 women aged 16–39. Median spine T score was −1.3 (range between 0.5 and −3.7), and hip T score was −1.2 (range between 0.8 and −3.3). A negative correlation was found between endometrial thickness and the presence of osteopenia or osteoporosis (r = −0.5, p = 0.013). Despite our recommendations, only eight of 14 women agreed to hormonal treatment or contraception. One woman who received treatment had a thromboembolic event. Routine health care for women with PWS should include gynecological examinations. The gynecological evaluation should include external genital examination, assessment of hygiene, obtaining a blood sample for hormone levels, and documenting a history of sexual experience or sexual abuse. Hormonal treatment or contraception should be offered when appropriate.

Background & Aims. Non-alcoholic fatty liver disease (NAFLD) is the most common liver dis... more Background & Aims. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in all ages that may cause significant morbidity and mortality. The pathogenesis of the disease is not fully elucidated but genetic factors have a major role in the development of NAFLD. Prader-Willi syndrome (PWS) is a neurogenetic, multisystemic disorder in which the main symptom is lack of satiety with uncontrolled eating and severe obesity. Despite obesity, NAFLD is relatively rare in PWS. The aim of this study was to assess whether known NAFLD-associated small nucleotide variants (SNVs) play a role in the protection from NAFLD in PWS. Approach & Results. Using targeted amplicon next generation sequencing, we studied DNA from patients with PWS and genotyped 13 SNVs that were previously associated with high risk for NAFLD. The study population included 142 (69 females) individuals with genetically confirmed PWS. Median age was 17.5 years, BMI z-score was 2.13 ± 1.9 and mean ALT and AST were 22 ± 20 units/L and 29 ± 17 units/L, respectively. Five of the 13 SNVs showed significantly lower frequency of the risk allele in our cohort compared to healthy population frequencies. Cumulative risk score for all 13 SNVs was also significantly lower in our cohort of PWS patients compared to the healthy population (adjusted p-value, 1.85E-5). Furthermore, it was found that Ashkenazi Jews have lower frequency of the risk alleles of NAFLD. Conclusions. Our results show that genetic factors may protect patients with PWS from developing NAFLD. Larger scale studies should be performed to confirm our findings.

Research Square (Research Square), Jul 21, 2022

Purpose: Understanding the normal range of laboratory values as pertained to different age groups... more Purpose: Understanding the normal range of laboratory values as pertained to different age groups and males or females is paramount in health care delivery. We aimed to assess the distribution of glucose levels by age and sex in the general population of children using a large-scale population-based cohort. Methods: A retrospective study with real-world de-identi ed data from a large, state mandated health fund in Israel among children aged 2 to 18 years old between 2006 and 2019. Age, sex, and BMI differences in mean glucose levels were evaluated using 3-way Anova. Results: Study included 130,170 blood samples from 117,411 children, 53.3% were female. After adjusting for age boys had higher glucose levels than girls, with a mean of 89.21 ±8.66 mg/dL vs. 87.59 ±8.35 (p<0.001). Compared to the 15 to 18 year-olds (88.49 mg/dl ±7.63), 2 to 5 year-olds had lower glucose levels (84.19 ±10.65, (p<0.001)), 11 to 14 year-olds had higher glucose (90.40 ±7.42 (p<0.001)) and 6 to 10 year-olds showed no difference (88.45 ±8.25). Among our cohort, 33.0% (n=42,991) had a BMI percentile record the same year as their glucose test result. There was a weak yet signi cant positive association between blood glucose levels and BMI (Pearson coe cient <0.1). Conclusions: Our large cohort indicates that boys have higher glucose levels than girls, as do adolescents compared to younger children. This nding is important for the delivery of adequate health care, screening for illness and avoiding unnecessary investigations and tests.

Diabetes Care, May 1, 1981

Postgraduate Medical Journal, Jun 1, 1986

We studied two sisters who developed large non-toxic goitres in adolescence. Deiodinase deficienc... more We studied two sisters who developed large non-toxic goitres in adolescence. Deiodinase deficiency was diagnosed by a rapid thyroid uptake ofradioactive iodine (RAI) at 2 hours associated with a marked fail in thyroidal 131I by 24 hours. Serial RAI scans in the second patient documented evolution of the iodine-deficient state. Conservation of intra-thyroidal iodine stores was maintained by avid iodine uptake and failure to release organified 1311. With progressive loss of inorganic iodine, hypothyroidism developed, associated with a rise in serum TSH which further exacerbated the loss of iodine. Treatment with L-thyroxine resulted in an improvement ofthyroid function, but normalization was achieved only after small doses of Lugol's iodine were administered. These studies illustrate the variable nature and late onset of an inborn error of thyroid metabolism. This family supports an autosomal recessive mode of inheritance for deiodinase deficiency. We have documented progression from a euthyroid to hypothyroid state resulting from decompensation of iodine conservation mechanisms. Case reports Case I This 23 year old woman was born in Jerusalem to nonconsanguineous Tunisian Jewish parents. Except

The Journal of Clinical Endocrinology and Metabolism, Apr 1, 1977

Human pancreatic polypeptide (HPP) was localized in surgically obtained human pancreas by immunoc... more Human pancreatic polypeptide (HPP) was localized in surgically obtained human pancreas by immunocytochemical electron microscopy. HPP was localized to the secretory granules of cells distinct from the alpha, beta, or delta cells of endocrine islets. The PP cells in 10 patients surveyed were most frequently located in the periphery of the islets. Immunolocalization distinguishes a fifth endocrine cell type in human islets which distinct ultrastructurally by its smaller granule diameter and lack of PP immunoreactivity.

Postgraduate Medical Journal, Jul 1, 1986

Iodine-induced hyperthyroidism can develop even in the presence of an otherwise normal gland. One... more Iodine-induced hyperthyroidism can develop even in the presence of an otherwise normal gland. One of the less common sources of iodine is tablets of seaweed, sold over the counter without prescription. We report the case of a 72 year old female who developed clinical and laboratory evidence of hyperthyroidism while ingesting sea-kelp (Vitalia) tablets. Six months after stopping the tablets, the symptoms and laboratory evidence of hyperthyroidism had disappeared. No evidence of pre-existing thyroid disease was found.

Journal of Internal Medicine, Aug 1, 1990

. Compensated hypothyroidism was diagnosed in a 36‐year‐old female who presented with breast tend... more . Compensated hypothyroidism was diagnosed in a 36‐year‐old female who presented with breast tenderness and mild galactorrhoea. T4 was 5.8mcg dl−1 and T3RU was 22.5%, while TSH and prolactin were very mildly elevated (6.5mU ml−1 and 26.1 ng ml−1, respectively). The TRH test showed an exaggerated response. TSH increased to 43 mU ml−1, and prolactin levels reached 161 ng ml−1. Treatment with T4 decreased the TSH and prolactin levels to within the normal range, and prevented the galactorrhoea. The case presented here demonstrates that galactorrhoea can be present even with mild hypothyroidism.

Regulatory Peptides, May 1, 1982

An antiserum to purified catfish pancreatic somatostatin-22 (anti-CPS-22) was obtained and a radi... more An antiserum to purified catfish pancreatic somatostatin-22 (anti-CPS-22) was obtained and a radioimmunoassay developed which was highly specific for CPS-22. Displacement by tetradecapel~tide somatostatin (SST-14) was at least 1000-fold less than with homologous peptide. A discrete population of catfish islet cells were stained in sections treated with anti-CPS-22, which appeared to be somatostatin containing D-cells identified by characteristic granule morphology on electron microscopy. Both SST-14 and CPS-22, presumably the products of two non-allelic somatostatin genes, have been identified in catfish pancreatic islets (Andrews, P.C. and Dixon, J.E. (1981) J. Biol. Chem., 256, 8267). Using the anti-CPS-22 and anti-SST-14 assays, it was estimated that CPS-22 comprised approximately 90%, and SST-14 5-10% of total immunoreactive catfish pancreatic somatostatin. The anti-CPS-22 assay was used on other pancreatic extracts to look for non-allelic forms of somatostatin. Anti-CPS-22 reacted poorly with pigeon pancreas extracts, but in rat pancreas extracts there was as much immunoreactive somatostatin measured with the CPS-22 as with the SST-14 assay. Similar immunochemical determinants in fish and rat somatostatins were suggested by parallel displacement of labeled CPS-22 from anti-CPS-22 with pancreatic extracts. Chromatography on Biogel P-60 in 2.5 M

Archives of Sexual Behavior, 2021

Many genetic disorders associated with intellectual disability are characterized by unique behavi... more Many genetic disorders associated with intellectual disability are characterized by unique behavioral phenotypes which may have serious psychological consequences such as increasing the risk for sexual abuse (SA). Prader–Willi Syndrome (PWS), a severe neurogenetic syndrome with uncontrollable hyperphagia and high threshold for pain, is an excellent example of this issue. The absence of reports on SA in PWS highlights the lack of awareness to the topic. Our aim was to report on SA in individuals with PWS, describe its unique characteristics, and offer recommendations for its prevention. Caregivers of all individuals with genetically confirmed PWS living in the only two residential facilities designated for PWS in Israel were interviewed for a history of sexual behavior and abuse, and medical data were collected from their files. SA was reported in a quarter of the sample. In most of the cases (78%), food reward was used by the perpetrators to attract their victims. Age at SA ranged from 11 to 29 years. Most of the individuals did not disclose the event and some continued to initiate inappropriate sexual activity to obtain food. Characteristics unique to PWS, such as food-seeking behaviors and high threshold for pain, likely contribute to the risk for SA. These findings suggest that syndrome-specific programs for SA prevention should be considered for individuals with any genetic syndrome with behavioral problems that may increase SA risk.

Title: Toward Prenatal diagnosis of Prader Willi Syndrome Objectives: To characterize the fetal p... more Title: Toward Prenatal diagnosis of Prader Willi Syndrome Objectives: To characterize the fetal phenotype of a cohort of individuals with confirmed diagnoses of PWS. Methods: We interviewed mothers of 106 individuals with PWS to obtain information about the pregnancy of their affected child. For 47 pregnancies of children younger than 10 years, we also reviewed the obstetric ultrasound and detailed obstetric history from medical records. We compared the PWS pregnancies with those of the sibling closest in age. Results: Decreased fetal movement, intra-uterine growth retardation (IUGR), asymmetrical intra-uterine growth with a significant discrepancy between abdomen and head circumferences, and polyhydramnios were found in 88%, 65%, 43% and 34%, respectively. In 101/106 (95%) pregnancies, at least one abnormality was documented prenatally. A combination of 2, 3 and 4 abnormalities was found in 27%, 29% and 24% of pregnancies, respectively. The combination of asymmetrical intra- uterin...

American Journal of Obstetrics and Gynecology, 2020

CONCLUSION: Our data indicates a concerning racial disparity in the administration of ACS in wome... more CONCLUSION: Our data indicates a concerning racial disparity in the administration of ACS in women with preterm birth between 23 and 34 weeks' gestation. Non-Hispanic white women are much more likely to have received ACS compared to non-Hispanic black and Hispanic women. Further research is needed to identify the reasons for this concerning disparity.

Background: We characterized the spectrum and etiology of hypogonadism in a cohort of Prader-Will... more Background: We characterized the spectrum and etiology of hypogonadism in a cohort of Prader-Willi syndrome (PWS) adolescents and adults. Methods: Reproductive hormonal profiles and physical examination were performed on 19 males and 16 females ages 16–34 years with PWS. Gonadotropins, sex-steroids, inhibin B (INB) and anti-Mullerian hormone (AMH) were measured. We defined 4 groups according to the relative contribution of central and gonadal dysfunction based on FSH and INB