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Biomedical subjects

M Berezin

Publications and source records attributed to M Berezin.

At least 19 recordsLinked to original sources
PubMed2005

Management of pituitary apoplexy: clinical experience with 40 patients.

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+/-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.

Adenoma↗
PubMed2000

Mutation analysis of the MEN1 gene in Israeli patients with MEN1 and familial isolated hyperprolactinemia.

Multiple endocrine neoplasia type 1 (MEN-1) is characterized by hyperfunction and tumor formation of the parathyroids, anterior pituitary and endocrine pancreas. We carried out exon-specific, PCR-based DNA sequencing of the coding exons of the MEN1 gene in 8 Israeli MEN1 patients: 4 familial and 4 sporadic. We similarly analyzed Israeli families with a unique phenotype of isolated hyperprolactinemia (HPRL). Four mutations were detected in 4 MEN1 patients: C to T alteration at nucleotide 2608 resulting in R108X, and three intronic insertions/deletions (a 13 basepair (bp) deletion and a 1 bp insertion both in intron 1, and a 2 bp insertion in intron 3) leading to exonic frame shifts as they encompass the splice junctions. An additional patient exhibited a compound mutation: a G to T change at position 7614 resulting in E463X, and insertion/deletion of 9 bp at position 7622-7630 resulting in EAE466-468X. Haplotype analysis showed no segregation of phenotype with 11q13 markers in 4 familial HPRL, and no men 1 germline mutations were detected in three representative individuals, from 3 families. Our results confirm that men 1 gene germline mutations occur in the majority of patients with clinically diagnosed MEN1, and that familial HPRL is a genetically distinct disorder.

Adolescent↗
PubMed1999

Increase in PDX-1 levels suppresses insulin gene expression in RIN 1046-38 cells.

RIN1046-38 cells (RIN-38) exhibit a passage-dependent reduction in both basal and glucose-regulated insulin secretion, accompanied by decreased insulin content. In an attempt to explain the mechanism of the gradual decrease in insulin production in cultured cells, we analyzed the insulin promoter activity and the levels of an important trans-activator of the insulin gene, PDX-1, as a function of aging in culture. We demonstrate that the decrease in insulin content and secretion is reflected in decreased promoter activity and is associated with a decrease in E47 and BETA2 nuclear factors, but with a paradoxical 3-fold increase in PDX-1 protein levels. To dissect the effect of increased PDX-1 from the decrease in the additional transcription factors on insulin promoter activity, we overexpressed PDX-1 protein in low passage RIN-38 cells by recombinant adenovirus technology. PDX-1 overexpression did not reduce E47 and BETA2 levels, but was sufficient to suppress rat insulin promoter activity in a dose-dependent manner. The fact that PDX-1 levels participate in trans-activation of insulin promoter activity was demonstrated in HIT-T15 cells. Treating HIT-T15 cells with 1-2 multiplicity of infection of AdCMV-PDX-1 increased rat insulin promoter activity, whereas higher doses repressed insulin promoter activity in these cells as in RIN-38 cells. Our data demonstrate that PDX-1 regulates transcription of the insulin gene in a dose-dependent manner. Depending on its nuclear dosage and the levels of additional cooperating transcription factors, PDX-1 may act as an activator or a repressor of insulin gene expression, such that low as well as high doses may be deleterious to insulin production.

Adenoviridae↗
PubMed1998

Enhanced erythrocyte Na+/H+ exchange predicts diabetic nephropathy in patients with IDDM.

Diabetic nephropathy develops in a subset of patients with an apparently hereditary predisposition. Microalbuminuria and elevated arterial pressure have been proposed as predictors of nephropathy but both appear when renal damage is impending. Enhanced sodium-hydrogen exchange in the cell membranes of diabetic patients is an early marker of diabetic nephropathy but its predictive value has not been assessed. In this study, sodium-hydrogen exchange was measured in erythrocytes as an initial velocity of amiloride-inhibited H+ efflux (pH 6.35-6.45) into a Na+ - containing medium (pH 7.95-8.05) in 156 non-microalbuminuric insulin-treated diabetic patients (98 women, 58 men, age 33+/-8 years, diabetes duration prior to enrollment 15+/-4 years) during 8 years of follow-up. Enhanced erythrocyte sodium-hydrogen exchange predicted diabetic nephropathy alone and in association with a familial tendency to hypertension/nephropathy with 86 and 96% sensitivity, and 80% specificity. Thus, sodium-hydrogen exchange appears to detect a subset of diabetic patients prone to develop renal damage, in whom a more intensive treatment modality might be considered.

Adult↗
PubMed1998

Enhanced Na+/H+ exchange in Cushing's syndrome reflects functional hypermineralocorticoidism.

BACKGROUND: Patients with Cushing's syndrome exhibit a bimodal distribution of maximal rates of the erythrocyte amiloride-sensitive Na+/H+ exchange (NHE). Enhanced erythrocyte NHE has recently been found in patients with primary aldosteronism. OBJECTIVE: To test the hypothesis that occult hypermineralocorticoidism in a subset of patients with Cushing's syndrome is responsible for the greater than normal NHE. METHODS: NHE was measured as maximal initial rate (Vmax) of amiloride-inhibited efflux of H+ into an alkaline Na+-containing medium, for 47 patients with hypercortisolism (20 with pituitary adenomas, 18 with adrenal adenomas, and nine with ectopic production of adrenocorticotropin). Clinical appearance, blood pressure levels, plasma aldosterone and deoxycorticosterone levels, serum electrolytes, and urine (tetrahydrocortisol plus 5-alpha-tetrahydrocortisol) : tetrahydrocortisone ratios were assessed for all patients. Twenty patients (10 with greater than normal NHE and 10 with low-to-normal NHE) were randomly selected from 47 patients with hypercortisolism, and treated with 200 mg/day spironolactone for 7 days. NHE in these patients was assessed before starting the treatment and 2 days after its cessation. RESULTS: Greater than normal NHE (Vmax) was associated with peripheral edema, high diastolic blood pressure, hypokalemia, and high urine (tetrahydrocortisol plus 5-alpha-tetrahydrocortisol) : tetrahydrocortisone ratios. The enhanced NHE was rapidly normalized by treatment with spironolactone. CONCLUSION: Erythrocyte NHE in patients with hypercortisolism and functional hypermineralocorticoidism is greater than normal due to incomplete peripheral conversion of cortisol (which binds to mineralocorticoid receptors) into metabolically inactive cortisone.

Adult↗
PubMed1997

[Red cell Na+/H+ exchange and role of protein kinase C in its stimulation in diabetes mellitus, essential hypertension and nephropathy].

Na+/H+ exchange (NHE) was measured as maximal initial velocity of pH-dependent H+ efflux from red cells into an alkaline medium containing Na+ in patients with insulin-dependent or noninsulin-dependent diabetes, with and without hypertension and in normoglycemic, essential hypertensives and normal controls (50 subjects in each subgroup). Maximal velocities of NHE were found in microalbuminuric patients in all subgroups, and NHE correlated with the rate of micro-albuminuria (r = 0.61, p = 0.02). Daily insulin requirements were greater in those with elevated NHE (84 +/- 8 vs 42 +/- 4 U/day). There was no correlation between NHE and levels of plasma glucose, HbA1 and plasma aldosterone and lipid profile and PRA. NHE was correlated with plasma prolactin (r = 0.51, p = 0.02) and PTH r = 0.24, p = 0.05). In uremic patients, NHE was inversely correlated with creatinine clearance (r = -0.48, p = 0.03). Since calphostin C, a selective inhibitor of protein kinase C, lowered increased NHE in vitro, the protein kinase C-dependent pathway of the exchanger regulation was concluded to be responsible for NHE activation in diabetes mellitus and essential hypertension.

Adult↗
PubMed1997

Amiloride-sensitive Na+/H+ exchange in erythrocytes of patients with NIDDM: a prospective study.

Intensive treatment of non-insulin-dependent diabetes mellitus (NIDDM) decreases the rate of microvascular complications, but is associated with increased incidence of cardiovascular morbidity. Enhanced permeability of plasma membranes for sodium (e.g. sodium-hydrogen exchange, NHE) may predict the subset of diabetic patients for whom intensive modalities of treatment are indicated despite their potential risk. However, the accuracy of NHE as a marker of microangiopathy has not been assessed. In this study NHE as initial velocity of amiloride-inhibited H+ efflux from erythrocytes (pHi 6.35-6.45) into an Na(+)-containing medium (pHo 7.95-8.05), was estimated during 8 years of follow-up in 138 non-microalbuminuric diabetic patients (74 women, 64 men, age 52 +/- 4 years) treated with antihyperglycaemic drugs for 14 +/- 2 years. Appearance of microalbuminuria, overt proteinuria, azotaemia and retinopathy was assessed annually. Enhanced erythrocyte NHE predicted diabetic nephropathy alone and in association with a family history of hypertension and/or nephropathy with a sensitivity of 86 and 93%, respectively. No association was found between NHE and retinopathy in NIDDM. It is concluded that assessment of erythrocyte NHE can identify a subset of patients likely to develop renal damage, for whom an aggressive treatment approach might be considered.

Albuminuria↗
PubMed1997

Gynecomastia following spinal cord disorder.

Gynecomastia, an excessive development of the mammary glands in men, is a known phenomenon among patients with spinal cord disorder, yet in the last 50 years it has not been fully described in relation to spinal cord disorder. Over a period of 2 years, six patients with spinal cord disorder (4 secondary to a traumatic injury, 1 to decompression sickness, and 1 to transverse myelitis) manifested gynecomastia. The onset of gynecomastia occurred between 1 to 6 months after injury. These patients are presented along with a review of the possible causes for gynecomastia and a suggested workup routine. A clinical examination for the presence of gynecomastia should be performed for every patient with spinal cord disorder and a thorough endocrinological workup should follow to rule out malignancy and reassure the anxious patient undergoing a disruption of his body image.

Adolescent↗
PubMed1997

Hyperprolactinemia in postmenopausal women.

OBJECTIVE: To study the clinical cause and course of hyperprolactinemia in postmenopausal women. DESIGN: Retrospective case-note study. SETTING: Tertiary care hospital. PATIENT(S): Six postmenopausal women with hyperprolactinemia. MAIN OUTCOME MEASURE(S): Clinical history and physical examination, serum levels of PRL, LH, FSH, computed tomography (CT) of the pituitary gland before and after treatment with bromocriptine. RESULT(S): At presentation, the mean age was 57.5 +/- 7.5 SD years. The mean level of PRL was 1,427 +/- 1,599 ng/mL (1,427 +/- 1,599 micrograms/L). All women suffered from secondary amenorrhea for a mean duration of 31.8 +/- 5.6 years. Five of six had galactorrhea at some time in the past. Pituitary imaging revealed a pituitary macroadenoma in four women, an enlarged sella suggestive of a pituitary macroadenoma in one woman, and a microadenoma in one. After treatment with bromocriptine, the PRL level decreased in all women to within normal limits. Five of six women developed hot flushes after the PRL level returned to normal. CONCLUSION(S): Most cases of hyperprolactinemia in postmenopausal women are due to macroadenoma rather than microadenoma, the common finding in younger women. The clinical course is suggestive of a prolonged disease that was not detected earlier, although clinical signs were present. These findings are suggestive of an enlargement of microadenomas to macroadenomas as time passes.

Adenoma↗
PubMed1997

A pituitary mass and hypopituitarism: improvement after corticosteroid therapy.

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.

Adult↗
PubMed1995

Autoantibody profile in the sera of women with hyperprolactinemia.

Prolactin (PRL) has been implicated as an important in vivo modulator of cellular and humoral immunity. In order to elucidate the impact of elevated serum PRL levels on the immune system, we measured circulating autoantibodies in the serum of 33 hyperprolactinemic (HPRL) women and in 19 healthy women with normal PRL levels. All sera were examined for the presence of autoantibodies against 15 different antigens, including: ssDNA, dsDNA, histones (H2AH2B), Sm, RNP, SS-A/Ro, SS-B/La, cardiolipin, Scl-70, Jo1, collagen, glomerular basement membrane (GBM), pyruvate dehydrogenase (PDH), proteinase-3 (PR3) and MPO. Twenty-five of 33 (75.7%) HPRL women were found to have at least one autoantibody, while none of the 19 women with normal PRL had any. Eight HPRL women had seven or more (up to nine) different autoantibodies. Some of the autoantibodies were more frequently expressed than others, namely: anti-ss-DNA, anti-dsDNA, anti-Sm, anti-PDH and anti-SS-A/Ro. Autoantibodies to the autoantigens tested are common in a variety of autoimmune and rheumatic disorders including systemic lupus erythematosus (SLE), Sjögren's syndrome, mixed connective tissue disease (MCTD), scleroderma, primary biliary cirrhosis (PBC), polymyositis/dermatomyositis and vasculitis. Yet none of the HPRL women whose serum was found to contain high titers of autoantibodies presented with symptoms related to the respective autoimmune disorders. Our results support the role of PRL in the regulation of immune responses in man.

Adult↗
PubMed1995

Prolactinoma in 53 men: clinical characteristics and modes of treatment (male prolactinoma).

The data of 53 men treated for hyperprolactinemia were reviewed retrospectively to determine the efficacy of the medical and surgical treatment. The clinical assessment, radiological and neuro-ophthalmological investigations and hormonal measurements were performed before treatment as well as during the follow-up period. Imaging evaluation included computed tomography and/or nuclear magnetic resonance of the pituitary. The hormonal profile examined was PRL, FSH, LH and testosterone, as well as TSH, T4, T3 and cortisol. Thirty patients were treated solely by dopamine agonists (DA), twenty-two men had pituitary surgery in addition to DA treatment, and one patient was operated with no need for medical treatment. Decreased sexual function was the most frequent presenting symptom (85% of the men). Most of the patients had large invasive macroadenomas, with suprasellar extension. More than 40% had visual field defects. Baseline PRL (mean +/- SE) was 51,842 +/- 9,292 mU/L and decreased to a level below 575 mU/L in 70% of the patients after DA therapy. Mean testosterone, FSH, and LH levels increased slightly but significantly from the low baseline values. Complete clinical response to DA was achieved in 49% of the men and the tumor mass disappeared entirely in 21%, and incompletely in 42%. The surgical success rate (transsphenoidal or trans-cranial operation) was low--only one of the 23 patients operated recovered completely, and most of the patients were left with hormonal deficits and hyperprolactinemia. These findings indicate that continuous medical treatment with DA should be the preferred mode of treatment for male prolactinomas. Removal of these large tumors is recommended only when the tumors are life-threatening or if drug resistance or severe adverse reactions to DA develop.

Adolescent↗
PubMed1995

Familial prolactinoma.

BACKGROUND: Apart from the rare association with type I multiple endocrine neoplasia (MEN-1), familial types of prolactinoma have not been reported. PATIENTS AND MEASUREMENTS: Eight hyperprolactinaemic patients in four families and 18 of their first and second-degree relatives (parents, children and grandchildren) were examined. Hormone levels were measured, as well as other biochemical parameters. RESULTS: Prolactinoma was diagnosed in more than one member of each of the four families. CONCLUSION: Familial prolactinoma is a distinct entity which is probably due to a genetic mutation promoting lactotroph proliferation.

Adolescent↗
PubMed1994

Acute leukemia relapse presenting as central diabetes insipidus.

BACKGROUND: Diabetes insipidus due to leukemic involvement of the central nervous system has been described previously in several patients. Although the timing of the diabetes insipidus onset in relation to the leukemia is variable, it has not been described previously as the first manifestation of leukemia relapse. METHODS: Two cases of leukemia relapse presenting as central diabetes insipidus are described and the literature is reviewed. RESULTS: Clinical data of 29 of the 39 reported cases were available. The median age was 46 years, with no gender predominance. Seventy-three percent had acute nonlymphocytic leukemia, and deletion of chromosome 7 or monosomy 7 was the predominant cytogenetic abnormality. No temporal relation between the onset of diabetes insipidus and the leukemia was found. In none of the previously reported cases was diabetes insipidus the first manifestation of the leukemia recurrence. CONCLUSIONS: The temporal relationship between diabetes insipidus and leukemia is inconsistent. The former may precede, follow, or present concomitantly with the latter. Two cases of diabetes insipidus as the presenting sign of leukemia relapse are reported.

Adult↗
PubMed1993

Effects of bradykinin on the canine proximal colon.

The canine proximal colon set up in Ussing chambers responded to the serosal addition of bradykinin (BK) with changes in short-circuit current (Isc). Two preparations were used to analyze these effects - an innervated mucosal preparation and a 'functionally nerve-free' epithelial preparation. The specific questions that this study sought to answer were (1) is there a significant neural component to the effects noted?, and (2) what is the receptor subtype involved? BK produced dose-dependent increases across both the mucosa and the epithelial preparations. A secondary decrease in Isc was noted in the mucosal but not the epithelial preparation. Tetrodotoxin (TTX) significantly inhibited the magnitude of mucosal responses and delayed their onset as well, indicating the presence of a significant neural component. Addition of the B2 antagonist, D-Arg0[Hyp3,Thi5,8, D-Phe7]BK produced a surmountable inhibition of the responses to the agonist. The B1 selective agonist, des-Arg9BK produced increases in Isc across both preparations, though TTX had no significant effects on these responses. Cross-desensitization was seen between BK and des-Arg9 BK. However, since the B1 selective antagonist, des-Arg9[Leu8]BK acted as a partial agonist in our preparation, these effects could not be defined further. Clearly, B2 receptors are involved in mediating canine colonic BK responses, however the role of B1 receptors in this tissue requires further definition.

Amino Acid Sequence↗
PubMed1992

[Anorexia nervosa in a young diabetic].

Coexistence of diabetes mellitus and anorexia nervosa has been noted in the past 2 decades. The nature and treatment of diabetes offer numerous opportunities for the anorectic patient to lose weight. Improper adjustment of the insulin dose, failure to inject insulin, clandestine vomiting and failure to provide urine samples allow the anorectic diabetic to achieve morbid weight loss. The treatment of patients with both conditions is difficult; behavioral management combined with psychotherapy was found to be most effective. An illustrative case is presented.

Adolescent↗