Moshe Hadani - Academia.edu (original) (raw)

Papers by Moshe Hadani

Pituitary, Mar 20, 2019

Purposes To test if the antibody array strategy could be utilized to simultaneously detect the se... more Purposes To test if the antibody array strategy could be utilized to simultaneously detect the secretion of multiple growth factors by human pituitary GH-adenomas and to measure octreotide-induced alterations. Methods Specimens of human pituitary adenomas were cultured and incubated with or without octreotide for 24 h. Conditional media were analyzed by human growth factor antibody array and VEGF concentrations were measured by ELISA. Media were also analyzed for GH concentrations. p21 expression levels were examined by Western blot of the specimens lysates. Results The antibody arrays successfully identified growth factors secreted by GH-adenomas in vitro. Octreotide treatment induced both elevations and reductions in growth factors secretion. GH response to octreotide was measured, and in this small-sized study resistant and sensitive GH-adenomas presented with no unique secretome pattern of each of the groups. Octreotide-induced VEGF alterations analyzed by the antibody array and by ELISA were not fully matched. Conclusions This study suggests that the broad proteomic strategy of antibody arrays may be utilized to study the growth factors secretion pattern of GH-adenomas and its regulation by somatostatin analogs or other compounds.

Intracerebral hemorrhage in an infant with idiopathic thrombocytopenic purpura: approach to the surgical management

PubMed, Nov 1, 1993

We describe a 21-month-old female infant with severe idiopathic thrombocytopenic purpura (ITP), w... more We describe a 21-month-old female infant with severe idiopathic thrombocytopenic purpura (ITP), who presented in coma with signs of cerebral herniation. CT scan revealed a right temporo-parietal intracerebral hemorrhage. The patient underwent immediate craniotomy and the hematoma was drained. Marked improvement in her neurological status, as well as postoperative resolution of the intracranial hemorrhage, were noted. Three months after the operation she recovered from the ITP. We emphasize the option of performing craniotomy without splenectomy in ITP infant patients.

A pituitary mass and hypopituitarism: improvement after corticosteroid therapy

PubMed, 1997

Lymphocytic hypophysitis of the anterior pituitary is a rare autoimmune disease, invariably diagn... more Lymphocytic hypophysitis of the anterior pituitary is a rare autoimmune disease, invariably diagnosed either by surgical biopsy of the adenohypophysis or at autopsy. The current report describes the rapid development of hypopituitarism in a 42-year-old nulliparous woman with a large sellar mass, who did not undergo pituitary surgery. Transient regression of the sellar mass and partial improvement of the hypopituitarism was induced by treatment with corticoids. We suggest that the diagnosis of lymphocytic hypophysitis can be established clinically and that conservative treatment with corticoids should be considered prior to surgical intervention.

Magnetic Resonance Imaging-Guided, High-Intensity Focused Ultrasound for Brain Tumor Therapy

Neurosurgery, Nov 1, 2006

ABSTRACT Magnetic resonance imaging-guided high-intensity focused ultrasound (MRIgFUS) is a novel... more ABSTRACT Magnetic resonance imaging-guided high-intensity focused ultrasound (MRIgFUS) is a novel technique that may have the potential for precise image-guided thermocoagulation of intracranial lesions. The system delivers small volumetric sonications from an ultrasound phased array transmitter that focuses energy selectively to destroy the target with verification by magnetic resonance imaging-generated thermal maps. A Phase I clinical study was initiated to treat patients with recurrent glioma with MRIgFUS. To date, three patients with histologically verified recurrent glioblastoma multiforme have been treated with MRIgFUS. All patients underwent craniectomy 7 to 10 days before therapy to create a bony window for the ultrasound treatment. Sonications were applied to induce thermocoagulation of the enhancing tumor mass. Long-term radiological follow-up and post-treatment tissue specimens were available for all patients. MRIgFUS treatment resulted in immediate changes in contrast-enhanced T1-, T2-, and diffusion-weighted magnetic resonance imaging scans in the treated regions with subsequent histological evidence of thermocoagulation. In one patient, heating of brain tissue in the sonication path resulted in a secondary focus outside the target causing neurological deficit. New software modifications were developed to address this problem. In this first clinical report, MRIgFUS was demonstrated to be a potentially effective means of destroying tumor tissue by thermocoagulation, although with an associated morbidity and the inherent invasive nature of the procedure requiring creation of a bone window. A modified technology to allow MRIgFUS treatment through a closed cranium is being developed.

mTOR inhibitor Torin1 induces antiproliferative effects in MtT/E cell line and human pituitary tumors

15th International & 14th European Congress of Endocrinology, May 1, 2012

Annals of Otology, Rhinology, and Laryngology, Apr 1, 2000

Effects of selective somatostatin analogs and cortistatin on cell viability in cultured human non-functioning pituitary adenomas

Molecular and Cellular Endocrinology, May 1, 2008

Clinically "non-functioning" human pituitary adenomas (NFPA) constitute about 3... more Clinically "non-functioning" human pituitary adenomas (NFPA) constitute about 35% of pituitary adenomas. Somatostatin receptors (SSTR) expression in these adenomas has previously been described both in vitro and in vivo, without evidence for a correlation with tumor volume or the therapeutic efficacy of somatostatin analogs. This study was performed on 13 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". In addition, 3 growth hormone (GH)-secreting adenomas served as controls. A specimen from each tumor was dispersed and digested to isolate and culture the tumor cells, and the in vitro effects of SSTR2 and SSTR5 selective analogs and Cortistatin (CST) (100nM) on cell viability were studied. The quantity of viable cells was estimated using the XTT method. RNA purification of tumor samples and subsequent RT-PCR studies for SSTR2 and SSTR5 expression were performed. Somatostatin analog with high affinity for SSTR2 reduced cell viability by 20-80% in 8 of 13 NFPAs studied, all expressing the SSTR2. The inhibitory effect on cell viability of SSTR5-selective analog was 15-80% in 10 of 13 NFPAs studied, all but three expressing the SSTR5. CST, however, effectively reduced cell viability in only 6 NFPAs. Cell viability was inhibited by all peptides studied in 2 out of 3 GH-secreting adenomas, expressing both receptors. The third adenoma responded to SSTR2 analog and expressed only SSTR2. These results suggest the involvement of SSTR2 and SSTR5 in the anti-proliferative effects of somatostatin; however, CST is less potent in reducing cell viability in these tumors.

Myasthenic crisis precipitated by iodinated contrast agents

Neurology, Mar 1, 1986

Endocrine journal, 2005

Nitric oxide (NO), a highly reactive free radical, has been identified as a neurotransmitter in t... more Nitric oxide (NO), a highly reactive free radical, has been identified as a neurotransmitter in the central and peripheral nervous system. NO synthase (NOS) is the enzyme responsible for NO production from L-arginine and plays an important role in regulating the release of several hypothalamic peptides. In the pituitary, NO was found to increase growth hormone (GH) secretion in several in vitro and in vivo models. However, its role in human GH regulation is unknown. The aim of this study was to investigate the regulatory effects of NO on human GH and prolactin secretion using primary cell cultures of human fetal pituitaries and cultured hormone-secreting adenomas. Incubation of the human fetal pituitaries (21-24 wk gestation) in the presence of sodium nitroprusside (SNP; 1 mM), a NO donor, for 4 h resulted in a 50-75% increase in GH secretion, similar to the stimulatory effect evoked by growth hormone-releasing hormone (GHRH) (10 nM). However, fetal PRL secretion was not affected by SNP. GH release was also stimulated (40-70% increase) by SNP in 60% of the cultured GH-secreting adenomas studied. SNPinduced GH release was inhibited in both fetal and adenomatous cells by PTI0, a NO scavenger. The addition of cGMP (0.1-1 mM), the second messenger of multiple NO actions, enhanced fetal and adenomatous GH secretion by 55-95%. Neuronal NOS (nNOS) was expressed in normal (fetal and adult) human pituitary tissues and in GH-secreting adenomas. Examination of its functional expression using L-arginine (1 µM) yielded a 35% increase in GH release from cultured GH-secreting adenoma. This response was blocked by a NOS inhibitor with high selectivity for the neuronal enzyme and by a guanylyl cyclase inhibitor. In conclusion, NO stimulates human GH in cultured fetal pituitaries and GHsecreting adenomas. Cyclic GMP is probably involved in this hormonal regulation.

The Spine Journal, Sep 1, 2002

Acta neurochirurgica, Sep 1, 1993

An experimental study was designed to test the efficacy of a silicon barrier around a nerve root ... more An experimental study was designed to test the efficacy of a silicon barrier around a nerve root in order to prevent post operative epidural root scar adhesions. In 32 Sprague-Dawely rats a lumbar nerve root was microsurgically exposed bilaterally. In 16 animals a silicon tube, prepared with a longitudinai cut along half of its wall, was placed around one nerve root, while the contralateral side served as control. In another group of 12 animals, an autologous subcutaneous fat graft was placed on the exposed root. A group of 4 animals served as the control group which had not been operated upon. No post operative neurological deficit was observed in any of the animals. All animals were sacrificed 60 days after the operation and a bIock of tissue including the nerve roots were resected bilaterally without removal of the silicon or fat graft. Longitudinal and transverse cuts of the roots were stained with Haematoxilin and Eosin and with Masson's trichrome collagen stain. The roots in the "unoperated" control group were clean of any scar tissue. In 13 out of 16 animals, silicon prevented scar formation around the root as opposed to scar adhesions around control root on the contralateral side and as compared to unoperated roots. In the silicon group, adhesions penetrated only through the longitudinal narrow cut edge of the tube. Fat did not prevent adhesions in 11 out of 12 animals. We conclude that a silicon barrier is an effective method preventing post operative epidural root scarring in rats.

Acta neurochirurgica, Dec 2, 2004

Background. Pituitary apoplexy is a rare major clinical event with neurological, neuro-ophthalmol... more Background. Pituitary apoplexy is a rare major clinical event with neurological, neuro-ophthalmological, cardiovascular and hormonal consequences, resulting from an acute infarction of pituitary adenoma. We report our experience with a series of 40 patients presenting with pituitary apoplexy. Patients. Forty patients (27 males, 13 females; mean age, 51.2 yr) were admitted to our medical center between years 1985-2002 with acute presentation of pituitary apoplexy. Visual field defects occurred in 61% and ocular paresis in 40% of subjects. Sixty-three percent of adenomas were nonfunctional, and prolactinomas comprised 31%. Results. Thirty-four patients underwent transsphenoidal pituitary decompression. Visual fields and ophthalmoplegia improved in 81% and 71%, respectively. During follow-up (4.5 AE 5.4 yr), 79% of patients developed hypogonadotrophic hypogonadism, central hypothyroidism appeared in 54% and hypocortisolism-in 40% of patients. Permanent diabetes insipidus was diagnosed in 8%. Serial sellar MRI showed disappearance of pituitary tumor in 63% of operated subjects. Six patients (3 with PRL-secreting and 3 nonfunctional adenomas) were treated medically (corticosteroids, dopamine agonists), two patients (out of three) with visual deficits improved, and tumor shrinkage was noted in four. Conclusions. We present a large series of patients with pituitary apoplexy. Most subjects were operated, but six were treated conservatively. Almost all patients improved clinically, including those who were not operated, but hormonal deficiencies are very common.

Long Term Follow-Up of Spinal Cord Injury in the Autologous Macrophage Trial

Journal of Neurologic Physical Therapy, Dec 1, 2004

Ependymoblastoma in an HIV-positive hemophilic girl

Medical and Pediatric Oncology, 1994

A case of an HIV-positive hemophilic girl with an ependymoblastoma is presented. The unusual asso... more A case of an HIV-positive hemophilic girl with an ependymoblastoma is presented. The unusual association between the HIV-related condition and her brain tumor is discussed, speculating a viral mechanism involved in the induction of neoplasia.

PTR-3173 (Somatoprim™), a novel somatostatin analog with affinity for somatostatin receptors 2, 4 and 5 is a potent inhibitor of human GH secretion

Journal of Endocrinological Investigation, Sep 1, 2004

SS, a natural cyclic tetradecapeptide, is a potent suppressor of pituitary GH and TSH secretion. ... more SS, a natural cyclic tetradecapeptide, is a potent suppressor of pituitary GH and TSH secretion. At least five distinct SS receptor (SSTR) subtypes have been cloned and termed SSTRs 1-5. Both SSTR2 and SSTR5 regulate human GH and TSH secretion. Recently, a novel enzymatically stable SS analog, PTR-3173 (Somatoprim), with affinity for human SSTR2, SSTR4 and SSTR5, has been identified. This cyclic heptapeptide analog suppressed rat GH in vivo with no effect on insulin and minimal effect on glucagon secretion. Using primary cultures of human fetal pituitaries (20-24-week gestation) and GH-secreting adenomas, we studied the in vitro inhibitory effects of PTR-3173 on human pituitary secretion. PTR-3173 suppressed GH release from both fetal pituitaries (maximal suppression of 54% with 10 nM) and cultures of GH-cell adenomas (35% suppression with 100 nM). Octreotide and PTR-3173 had comparable inhibitory effects on GH secretion from fetal human pituitaries. TSH was mildly suppressed by PTR-3173, whereas ACTH secretion was not affected in fetal pituitary cultures. In cultures of eight GH-secreting adenomas, octreotide was superior to PTR-3173 in suppressing GH from two adenomas, PTR-3173 was more potent in three other tumors, and three adenomas did not respond significantly to either analog. PTR-3173 suppressed PRL in several mixed GH-PRL adenomas. In conclusion, PTR-3173, a novel SS analog with a unique SSTRs binding combination, is a potent in vitro suppressor of human GH. Combining this inhibitory effect with the lack of effect on insulin secretion, it is suggested that PTR-3173 may be clinically useful for the treatment of acromegaly.

Myasthenic crisis after intraxenous administration of iodinated contrast agent

Neurology, Aug 1, 1985

ABSTRACT

XIIIth National Meeting of the Italian Neuroepidemiology Association

Neuroepidemiology, 2008

Pediatric Craniocerebral Wounds from Plastic Bullets

The Journal of Trauma: Injury, Infection, and Critical Care, 1996

To review our experience with craniocerebral injuries caused by plastic bullets, and to delineate... more To review our experience with craniocerebral injuries caused by plastic bullets, and to delineate prognostic factors for outcome. Retrospective case series of 29 patients presenting with plastic bullet-induced craniocerebral lesions. Pediatric intensive care department of a tertiary care center. Outcome was poor in 10 patients, good in 11, and two and six patients were moderately and severely disabled, respectively. Statistical analysis showed prognostic significance of the admission Glasgow Coma Scale score, computed tomographic findings of intraventricular hemorrhage and midline shift, and metabolic studies including hypokalemia and hyperglycemia. Plastic bullet-induced craniocerebral injuries carry a lower morbidity and mortality rate compared with other gunshot wounds. However, plastic bullets do incur a significant risk of injury. Their use should be carefully regulated.

Central Nervous System Trauma, 1986

A simple and reliable method of quantifying tissue damage is described. This method, based on ato... more A simple and reliable method of quantifying tissue damage is described. This method, based on atomic absorption spectroscopic determinations of Na, K, and Ca concentrations in small brain samples, was applied to the rat middle cere- bral artery occlusion model (MCAo). At the infarct site by 24 hours, Na con- centration more than doubled, Ca concentration increased by >70%, and K concen- tration fell nearly 80%; these changes are consistent with a >80% disruption of cells. A remarkable acceleration of ionic shifts occurred between 4 and 6 hours after MCAo. At 4 hours, only 20-30% of the ionic shifts found at 24 hours had occurred; by 6 hours, 80-100% of the ionic shifts found at 24 hours had taken place. Since the measurements reflect ionic movement into and out of the tissue, they are likely to represent irreversible tissue damage. Although blood brain barrier breakdown may have contributed to an increased rate of ionic shifts, large ionic gradients must have been present between the extra- cellular space and the vascular compartment at 4-6 hours to drive the ionic shifts. Our results suggest an upper time limit of 4 hours for treatments of acute ischémie tissue damage in the rat MCAo model. The methods and analytical approach described may be useful for determining the time window for therapeu- tic intervention in acute CNS injuries, as well as for evaluating treatment effects.

In vivo simultaneous cortical and intracortical monitoring of cerebral blood flow and mitochondrial redox state in experimental animals

Optical Tomography and Spectroscopy of Tissue V, 2003

Monitoring of intra-mitochondrial NADH redox state is a common in-vivo technique in experimental ... more Monitoring of intra-mitochondrial NADH redox state is a common in-vivo technique in experimental animals and is rare in clinical studies. The combination of NADH monitoring with the Laser Doppler flowmetry for cerebral blood flow monitoring was described in various publications. Until now, very small effort was made to monitor NADH and CBF inside the cortex of experimental animals. The significance of this monitoring is in its application to experimental models of Parkinson"s disease or to clinical monitoring situations in the intensive care unit, when ICP is monitored. Here we compared the responses of the gerbil or rat brain to oxygen deficiency, monitored on the brain surface and in different depths. After the animals were anesthetized, the two common carotid arteries (gerbil) were isolated and prepared for following occlusion. The brain was exposed and two optical probes were located on its surface. Ischemia was induced by occluding the two carotid arteries, and anoxia was preformed by inhalation of pure N2. After recovery, one of the probes was inserted into the cortex (0.5-3mm) and a second ischemia or anoxia was preformed. The results showed that: 1. It is possible to monitor both CBF and NADH on the brain surface simultaneously with intracortical location. 2. The responses of the brain to ischemia or anoxia was smaller inside the cortex comparing to brain surface. 3. Negative correlation was found between CBF and NADH in both locations and models. In conclusion, this new model of simultaneously monitoring of CBF and NADH in different cerebral locations can shed light on various pathophysiological situations.