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Biomedical subjects

H Landau

Publications and source records attributed to H Landau.

At least 19 recordsLinked to original sources
PubMed1999

Improvement of the osteo-odonto-keratoprosthesis according to Strampelli: influence of diameter of PMMA cylinder on visual field.

BACKGROUND: In surgical management of severe corneal scarring, the osteo-odonto-keratoprosthesis (OOKP) according to Strampelli is recognised as the best choice. Nevertheless, the patients are handicapped by a restricted visual field. Enlarging the optical cylinder diameter should allow better rehabilitation of the patients. PATIENTS AND METHODS: A mathematical model to calculate the theoretical maximum visual field according to the length and the diameter of the cylinder of a keratoprosthesis was developed. The theoretical values were compared with our findings in three OOKP patients operated on in our hospital. RESULTS: The theoretical extent of the visual field with a cylinder of 8 mm length is 55 deg if the diameter is 3 mm and 62 deg if the diameter is 3.5 mm. The visual fields of our OOKP patients in both types of keratoprosthesis are, however, below the theoretically calculated values. Implantation of a prosthesis with a diameter of 3 mm produced horizontal visual fields of 30 and 36 deg in two patients. In one patient with a prosthesis diameter of 3.5 mm the field was 53 deg. CONCLUSIONS: The diameter of the visual field increases with the diameter and decreases with increasing length of the optical cylinder. In OOKP the implantation of a PMMA cylinder with a diameter of 3.5 mm is possible. The enlargement of the diameter of the optical cylinder leads to significant enlargement of the visual field. The size of the cylinder is limited by the diameter of the available root of the tooth.

Biocompatible Materials↗
PubMed1999

Neonatal Hyperinsulinism.

Hypoglycemia as a result of hyperinsulinism in the newborn (HI) is a clinically heterogeneous entity that presents a diagnostic and therapeutic challenge to the treating physician. Recent discoveries have shown that mutations in four different beta-cell genes cause HI. However, for many HI patients, the molecular etiology is unknown, and other genes might be involved. The study of the molecular biology of HI has led to a better understanding of pancreatic beta-cell physiology. In the future, this might result in the development of novel drugs for the treatment of both hyperinsulinism and non-insulin-dependent diabetes.

Journal Article↗
PubMed1998

Parathyroid adenoma after radiation in an 8-year-old boy.

We describe an 8-year-old boy who had asymptomatic hypercalcemia 4 years after radiotherapy involving the left orbit and lungs. A right parathyroid adenoma was diagnosed, and normocalcemia was achieved after its removal. Routine monitoring of serum calcium and phosphate levels is recommended for children after head and neck irradiation.

Adenoma↗
PubMed1997

A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism.

ATP-sensitive potassium (K[ATP]) channels are an essential component of glucose-dependent insulin secretion in pancreatic islet beta-cells. These channels comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member of the inward rectifier K+ channel family. Mutations in the SUR1 subunit are associated with familial hyperinsulinism (HI) (MIM:256450), an inherited disorder characterized by hyperinsulinism in the neonate. Since the Kir6.2 gene maps to human chromosome 11p15.1 (1,2), which also encompasses a locus for HI, we screened the Kir6.2 gene for the presence of mutations in 78 HI probands by single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses. A nonsense mutation, Tyr-->Stop at codon 12 (designated Y12X) was observed in the homozygous state in a single proband. 86Rb+ efflux measurements and single-channel recordings of COS-1 cells co-expressing SUR1 and either wild-type or Y12X mutant Kir6.2 proteins confirmed that K(ATP) channel activity was abolished by this nonsense mutation. The identification of an HI patient homozygous for the Kir6.2/Y12X allele affords an opportunity to observe clinical features associated with mutations resulting in an absence of Kir6.2. These data provide evidence that mutations in the Kir6.2 subunit of the islet beta-cell K(ATP) channel are associated with the HI phenotype and also suggest that the majority of HI cases are not attributable to mutations in the coding region of the Kir6.2 gene.

Animals↗
PubMed1996

Normal proinsulin processing despite beta-cell dysfunction in persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis).

Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a genetic disorder which causes severe hypoglycaemia in the neonate. The beta cells fail to respond to changes in blood glucose levels in all the stages of the disease, which often ends with NIDDM. Fasting insulin, intact proinsulin and des 31,32 split proinsulin levels were measured in PHHI patients with active disease, patients after partial pancreatectomy, and those in clinical remission. All but one of the pancreatectomized patients developed diabetes and were hyperglycaemic on evaluation. Fasting insulin was comparable in pancreatectomized and medically treated patients. Des 31,32 split proinsulin levels were much higher in pancreatectomized compared to non-pancreatectomized patients (10.7 +/- 2.5 vs 3.4 +/- 0.8 pmol/l, p = 0.001) and age-matched control subjects (3.8 +/- 1.4 pmol/l, p = 0.018). Also the ratio of des 31,32 split proinsulin to total insulin plus proinsulin-like peptides was higher in pancreatectomized patients (18.7 +/- 2.8 vs 7.2 +/- 0.8% in non-pancreatectomized patients, p = 0.001, and 6.8 +/- 2.1% in normal control subjects, p = 0.004). Furthermore, des 31,32 split proinsulin was the dominating species of proinsulin-like molecules in the pancreatectomized patients (62.7 +/- 1.6% vs 45.5 +/- 3.8%, and 49.0 +/- 3.2% in non-pancreatectomized patients and control subjects, respectively, p = 0.001 and p = 0.0002). Intact proinsulin levels, and the proinsulin percentage, tended to be higher in pancreatectomized patients; however, the differences did not reach statistical significance. All parameters were similar in non-pancreatectomized patients and age-matched control subjects. Subgroup analysis showed comparable proinsulin-like peptide levels in patients with active disease and those in apparent clinical remission. Fasting levels of insulin and proinsulin-like peptides were also measured in a larger group of healthy children and young adults. Insulin and des 31,32 split proinsulin increased with age, the differences being most prominent when the young age group (0-8 years) was compared to the older groups (8-16 and > 16 years). The fasting levels of plasma insulin were correlated with those of intact proinsulin and des 31,32 split proinsulin (r = 0.82 and 0.81, respectively). Fasting insulin, intact proinsulin and des 31,32 split proinsulin were correlated with BMI (r = 0.55, 0.56 and 0.53, respectively). In summary, relative hyperproinsulinaemia was noted only in PHHI patients with increased secretory demand following pancreatectomy, but not in patients with active disease or those in spontaneous clinical remission. These findings suggest that abnormal proinsulin processing is not an intrinsic feature of PHHI despite the severe beta-cell dysfunction.

Adolescent↗
PubMed1996

Healing of dentate or edentulous mandibular fractures treated with rigid or semirigid plate fixation--an experimental study in dogs.

The right mandibles of 40 dogs were fractured with a bending clamp, at a site being either dentate or edentulous, and treated with compression-plates or miniplates. After 1, 2, 4, 6, 8, 12 and 24 weeks the mandibles were examined by microradiography and histology. Some variation in the healing mode within the groups was observed, interindividual as well as intra-individual in different layers of the same mandible. Generally, healing displayed slightly more time-related progression with compression plates compared with miniplates and similarly in dentate fracture sites when compared with edentulous ones. The so-called indirect healing mode through cartilaginous callus was found to take place in the group with miniplates and edentulous fracture sites, whereas in the three other groups a type of direct bone healing through woven bone in the presence of more or less callus could be observed. The conclusions drawn from these findings are: that compression plates as well as miniplates are suitable for treatment of mandibular fractures in dogs, and the presence of teeth appears to exert a stabilizing effect on the fracture.

Animals↗
PubMed1996

Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.

Familial hyperinsulinism (HI) is a disorder of pancreatic beta-cell function characterized by persistent hyperinsulinism despite severe hypoglycemia. To define the molecular genetic basis of HI in Ashkenazi Jews, 25 probands were screened for mutations in the sulfonylurea receptor (SUR1) gene by single-strand conformation polymorphism (SSCP) analysis of genomic DNA and subsequent nucleotide sequence analyses. Two common mutations were identified: (I) a novel in-frame deletion of three nucleotides (nt) in exon 34, resulting in deletion of the codon for F1388 (delta F1388) and (II) a previously described g-->a transition at position-9 of the 3' splice site of intron 32 (designated 3992-9g-->a). Together, these mutations are associated with 88% of the HI chromosomes of the patients studied. 86Rb+ efflux measurements of COSm6 cells co-expressing Kir6.2 and either wild-type or delta F1388 SUR1 revealed that the F1388 mutation abolished ATP-sensitive potassium channel (KATP) activity in intact cells. Extended haplotype analyses indicated that the delta F1388 mutation was associated with a single specific haplotype whereas the 3992-9g-->a mutation was primarily associated with a single haplotype but also occurred in the context of several other different haplotypes. These data suggest that HI in Ashkenazi Jews is predominantly associated with mutations in the SUR1 gene and provide evidence for the existence of at least two founder HI chromosomes in this population.

Animals↗
PubMed1995

Recombinant mapping of the familial hyperinsulinism gene to an 0.8 cM region on chromosome 11p15.1 and demonstration of a founder effect in Ashkenazi Jews.

A gene for autosomal recessive familial hyperinsulinism (HI) (OMIM: 256450), a neonatal metabolic disease characterized by inappropriate insulin secretion in the presence of severe hypoglycemia, was recently mapped to a 6.6 cM interval between the markers D11S926 and D11S928 on chromosome 11p in 15 families (1). In the current study we evaluated six additional families and five new markers, and further localized the gene between D11S419 and D11S1310. Using genotype data from CEPH Version 7 and data generated from this study, this region was estimated to be 0.8 cM in length. Significant linkage disequilibrium between markers and the HI gene was observed over a region of 10.3 cM (11 pter-D11S926-D11S1308-11pcen) for Ashkenazi Jewish chromosomes. Haplotype analysis showed that 12 of 36 HI chromosomes, versus one of 36 non-HI chromosomes, bore a specific haplotype for D11S419-D11S902-D11S921 (p < 0.0007), strongly suggesting a founder effect in this ethnic group.

Alleles↗
PubMed1995

Hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) in clinical remission: high incidence of diabetes mellitus and persistent beta-cell dysfunction at long-term follow-up.

In persistent hyperinsulinemic hypoglycemia of infancy (PHHI), the long term outcome of the disease is not well documented. Previous reports suggested that partial pancreatectomy in infants does not endanger future islet function. We evaluated endocrine pancreatic function in 14 PHHI patients 6.5-21 yr after diagnosis. Eight underwent early subtotal pancreatectomy, and 6 were medically treated; all were in clinical remission. Intravenous glucose tolerance and C-peptide suppression tests were performed, with multiple determinations of hormone levels. The insulin response to glucose was blunted in all pancreatectomized and in 2 conservatively treated patients. Glucose disposal was reduced in 6 pancreatectomized patients and in 2 medically treated subjects. Six of the pancreatectomized patients, including two with normal glucose disposal at first evaluation, developed overt diabetes during puberty. None in the medically treated group became diabetic; however, only 2 patients have reached puberty. C-Peptide suppression in response to hypoglycemia was inadequate in 4 of 5 pancreatectomized and 3 of 5 nonpancreatectomized patients studied. These results show that children with PHHI have impaired insulin responses to glucose and lack of suppressibility of endogenous insulin secretion several years after clinical remission. Thus, the beta-cell defect responsible for the disease in infancy is not corrected with time despite the disappearance of spontaneous hypoglycemia. Insulin secretion seems more disturbed in pancreatectomized patients; the majority develop insulin-requiring diabetes during puberty. An effort should be made to treat PHHI patients medically to avoid pancreatectomy; this may reduce the incidence of diabetes at puberty.

Adolescent↗
PubMed1994

Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cM centromeric to the insulin gene.

Familial hyperinsulinism (HI) is the most common cause of persistent neonatal hyperinsulinaemic hypoglycemia. Linkage analysis in 15 families (12 Ashkenazi Jewish, 2 consanguineous Arab, 1 non-Jewish Caucasian) mapped HI to chromosome 11p14-15.1 (lod score = 9.5, theta = 0 at D11S921). Recombinants localized the disease locus to the 6.6 cM interval between D11S926 and D11S928. In Jewish families, association (p = 0.003) with specific D11S921/D11S419 haplotypes suggested a founder effect. This locus, which is important for normal glucose-regulated insulin secretion, represents a candidate gene for studies of other diseases of beta-cell dysfunction including non-insulin-dependent diabetes mellitus (NIDDM).

Chromosome Mapping↗
PubMed1994

Age as a determinant of the impact of growth hormone therapy on predicted adult height.

OBJECTIVE: Final adult height is determined by both childhood and pubertal growth. The later is a function of growth velocity and bone maturation, and both are regulated by growth hormone. In a study of the safety and efficacy of GH therapy, we analysed the impact of age on bone maturation and predicted adult height. PATIENTS AND METHODS: The subjects were 65 male patients with GH deficiency, as diagnosed by pharmacological or physiological tests, who participated in a multicentre trial and completed 3 years of hGH therapy. The age range at initiation of therapy was 3.1-15.7 years. Subcutaneous injections of hGH were given in a dose of 0.3 mg/kg/week, in thrice-weekly doses. Calculation of the adult height prediction was performed on annual growth parameters using the Bailey-Pinneau, TW-II and Roche methods. RESULTS: The rate of pubertal advancement correlated positively with the child's age at initiation of therapy. The bone age advanced in positive correlation with chronological age, and by the end of 3 years of hGH therapy the delta-bone age/delta-chronological age ratio increased to 1.5 for children with an age at start of therapy of 10.7 years. During the adolescent years, the predicted gained height over 3 years of therapy declined, in correlation with age, and became negative at a therapy-initiation age of 12.9 years. CONCLUSIONS: In a retrospective analysis of a group of children with heterogeneous GH secretory ability, GH induced acceleration of growth, around the age of normal puberty, advanced the age of pubertal onset and accelerated pubertal progression which, in turn, expedited bone maturation and thereby restricted predicted adult height gain from hGH therapy.

Adolescent↗
PubMed1994

Effect of long-term growth hormone therapy on bone age and pubertal maturation in boys with and without classic growth hormone deficiency.

We evaluated the effect of growth hormone (GH) therapy on bone age, pubertal maturation and predicted adult height in two groups of boys treated for 4 years: 40 growth hormone-deficient boys who had growth hormone response to provocative stimulation < 10 micrograms/L (GHD group) and 43 boys whose stimulated growth hormone > or = 10 micrograms/L (group with neurosecretory dysfunction (NSD)). All patients had a subnormal integrated concentration of growth hormone < or = 3.2 micrograms/L, height < -2 SD, growth velocity < 4.5 cm/yr, and bone age < or = -2 SD for chronologic age. Patients were treated with recombinant growth hormone, 0.1 mg/kg per dose given three times a week. The pretreatment height SD of the GHD group (-3.6 +/- 1.0) was less than that of the NSD group (-2.7 +/- 0.7; p < 0.001). After 4 years of therapy, both groups had catch-up growth (GHD group to -2.0 +/- 1.3 height SD (n = 35), and NSD group to -1.4 +/- 0.7 height SD (n = 32)); the rate of height SD gain was better in patients with GHD (p < 0.01). The response to growth hormone was inversely related to pretreatment chronologic age (p < 0.001). The Tanner-Whitehouse II predicted adult height improved for both groups: +9.3 +/- 7.7 cm in the GHD group, giving an adult height SD of -0.9 +/- 1.0, and +5.4 +/- 5.5 cm in patients with NSD, for an adult height SD if -0.8 +/- 0.7. Testosterone levels became higher in the NSD group after 2 years and remained higher at year 4. We conclude that patients respond favorably to growth hormone therapy and in a manner similar to patients with GHD. Initiation of therapy at a younger age gives a greater improvement in gained height and predicted adult height.

Age Determination by Skeleton↗
PubMed1993

Persistent hyperinsulinemic hypoglycemia of infancy: long-term octreotide treatment without pancreatectomy.

Eight patients with persistent hyperinsulinemic hypoglycemia of infancy who were treated with octreotide without pancreatectomy are described. All had severe, early-onset disease that would have required partial pancreatectomy had octreotide not been available. Along with octreotide, frequent feedings and raw cornstarch at night were required by all. Octreotide was given in three or four daily subcutaneous injections in four patients and in a continuous subcutaneous infusion with an insulin infusion pump in four. All had mild, transient gastrointestinal symptoms (vomiting, abdominal distention, steatorrhea) after the start of therapy. Asymptomatic gallstones were found in 1 patient after 1 year of treatment. No other long-term untoward effects were noted, including no detrimental effect on psychomotor development. Growth was not affected in five of six patients treated for more than 6 months. In five patients, octreotide was discontinued after 9 months to 5 1/2 years; patients were given diazoxide instead, two required percutaneous gastrostomy, and one 5 1/2-year-old child required no further treatment. The remaining three patients (aged 5 to 9 months) are still being treated with octreotide. We conclude that, with the use of octreotide, pancreatectomy can be avoided in some patients. Particularly in light of our findings of a high incidence of diabetes years after partial pancreatectomy, and clinical improvement after months to years of octreotide treatment, we believe that aggressive medical therapy, when effective, is preferable to partial pancreatectomy.

Diazoxide↗
PubMed1993

Cross-sectional and longitudinal study of the pituitary-thyroid axis in patients with thalassaemia major.

OBJECTIVE AND DESIGN: Thyroid dysfunction is known to occur frequently in thalassaemia major, but its prevalence and severity varies in different cohorts, and the long-term natural history is poorly described. We evaluated the pituitary/thyroid axis in thalassaemia major patients in a cross-sectional study and correlated abnormalities with indices of iron overload. Furthermore, the course of thyroid disease in thalassaemia major patients was assessed in a 15-year longitudinal study. PATIENTS AND MEASUREMENTS: Cross-sectional study: pituitary-thyroid axis function was examined in 37 patients (22 F, 15 M; aged 10-39 years, mean +/- SE = 21 +/- 1.4) out of a total of 43 who attended the Haematology and Endocrinology Clinics of Hadassah Hospital on a regular basis. The mean pretransfusion Hb level was 85 +/- 20 g/l, and all patients except one were treated with desferrioxamine (DF, mean +/- SE dose 20.2 +/- 2.6 mg/kg/day). Twenty-two had hypogonadotrophic hypogonadism (HH). Longitudinal study: 21 thalassaemia major patients were evaluated with TRH tests in 1976 and again in 1985. Fourteen of these and another eight were evaluated in both 1985 and 1991. RESULTS: Cross-sectional study: no patient had any clinical signs or symptoms of hypothyroidism; however, one had abnormally low T4, borderline low FT4 and normal T3 levels associated with an exaggerated TSH response to TRH consistent with mild hypothyroidism. This patient did not have a previous TRH test, but serial basal determinations over 7 years revealed a progressive decrease in thyroid function. Thirty-six patients had thyroid hormone levels within the normal range. Nine of these (24.3%) had only an exaggerated TSH response to TRH whereas seven others (19%) also had borderline elevated basal TSH levels. TSH response to TRH was not correlated with age, serum ferritin or liver function tests (ALT or GGT). Longitudinal study: mean TSH response to TRH decreased (P < 0.002), and mean T3 levels increased (P < 0.001) between 1975 and 1985. These findings are probably related to the initiation of DF treatment in 1981. During the last 6 years, four patients with previously normal TSH responses to TRH developed elevated peak TSH levels. Mean T3 concentrations decreased and TSH response to TRH increased significantly (P < 0.001 for both). CONCLUSIONS: (1) In this patient group the thyroid pituitary axis is less sensitive than the gonadal axis to iron-induced damage; only one out of 37 patients developed mild uncompensated hypothyroidism. (2) As opposed to the gonadal axis, the thyroid gland appears to fail before the central components of the axis. (3) Abnormal thyroid function may be reversible in the early stages. (4) Progression is variable, and it may take years to progress from normal to uncompensated hypothyroidism.

Adolescent↗
PubMed1993

Effect of timing of growth hormone administration on plasma growth-hormone-binding activity, insulin-like growth factor-I and growth in children with a subnormal spontaneous secretion of growth hormone.

Since normal pulsatile growth-hormone (GH) secretion displays a major and consistent surge during sleep, we studied the effect of timing of GH supplementation on plasma GH-binding protein activity (GH-BP), insulin-like growth factor-I (IGF-I) and growth. 34 prepubertal subjects (28 boys, 6 girls) aged 8-11 years, of short stature (< 2 SD for age), with a GH response to provocative test > 10 micrograms/l and a subnormal 24-hour GH secretion (< 3 micrograms/l), were randomly allocated to receive Bio-Tropin (recombinant GH, Bio-Technology, Israel) 0.81 IU/kg/week in 3 equally divided doses. GH was administered either at 8.00-10.00 h (M group), 14.00-16.00 h (AN group) or 19.00-21.00 h (NT group). Height velocity, IGF-I and GH-BP were determined prior to and after 6 and 12 months on GH therapy in the three groups. There was no significant difference between the three groups in the growth response, IGF-I and GH-BP increase, all of which increased significantly during GH therapy. Although GH levels after the injection decline to preinjection levels after 10 h, the changes induced by GH therapy, as reflected in IGF-I and GH-BP, last in the circulation long enough to prevent fluctuations in its action. The similarity of IGF-I and of GH-BP levels in the three treatment groups might explain the similar growth effects of the 3 protocols.

Carrier Proteins↗
PubMed1992

Predictors of growth response to growth hormone in otherwise normal short children.

Sixty prepubertal short children (39 boys) with heights less than 2 SD for age and gender were treated daily for 1 year with recombinant human growth hormone (GH), either 0.1 IU/kg (group 0.1, n = 32) or 0.05 IU/kg (group 0.05, n = 28). Reserve of GH was determined by at least one GH provocative stimulus and 24-hour continuous blood withdrawal to determine the integrated concentration of GH (IC-GH). All participants had a GH response to provocative tests greater than 10 micrograms/L. The height velocity (mean +/- SD) of the group as a whole increased from 4.46 +/- 1.02 to 7.59 +/- 1.65 cm/yr (p less than 0.001). The growth velocity of group 0.1 was significantly greater than that of group 0.05 (8.1 +/- 1.5 vs 7.0 +/- 1.65 cm/yr; p less than 0.01). Bone age did not advance more than 1 year during the treatment period. Growth velocity after 1 year of GH therapy was inversely correlated with the IC-GH in both groups, as was the pretreatment height velocity. We found no correlation of growth velocity during GH therapy with other measures such as parental heights, bone age/chronologic age ratio, maximal GH response to provocative tests, chronologic age, or pretreatment insulin-like growth factor I levels. We conclude that the best predictors for the 1-year growth outcome of short children with a normal GH response to provocative tests are the pretreatment growth velocity and the IC-GH. The short-term benefit from GH therapy in children with a normal growth velocity and a normal IC-GH is poor, whereas marked growth acceleration is noted in children with a low growth velocity and a low 24-hour IC-GH.

Age Determination by Skeleton↗