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Biomedical subjects

S Abdelhamid

Publications and source records attributed to S Abdelhamid.

At least 19 recordsLinked to original sources
PubMed1995

A new subset of mineralocorticoid hypertension with excess of 21-deoxyaldosterone and Kelly's-M1 steroid: clinical and morphological findings.

Ten cases of adrenal adenomas, one case with unilateral adrenal hyperplasia, and another case with apparent bilateral are reported, in whom an alternative pathway of aldosterone via 21-deoxyaldosterone is operative. They all manifested hypertension, low renin activity, low normal potassium values, as well as high urinary excretion rates of 21-deoxyaldosterone and its related metabolite Kelly's-M1 steroid. In all cases, urinary aldosterone metabolites (aldosterone-18-glucuronide and tetrahydroaldosterone) and aldosterone precursor 18-hydroxycorticosterone levels were normal. Hence, the adrenal lesions give rise to hyper-21-deoxyaldosteronism. 21-Deoxyaldosterone is a weak mineralocorticoid, and its elevated production in the presence of normal aldosterone can induce a pathological state of hypermineralocorticoidism. Adrenalectomy resulted in normalization of hypertension in six of eight and amelioration in two of eight cases. Six of seven adenoma cases examined as well as the case of unilateral adrenal hyperplasia were sensitive to ACTH. One of the seven adenomas and, as expected, the case with apparent bilateral hyperplasia were angiotensin responsive. Histologically and electron microscopically, the operated adenomas consisted predominantly of clear cells, characterized by mitochondria with tubulo-vesicular internal structure similar to those of the zona fasciculata (in contrast, our classical Conn's adenoma with normal 21-deoxyaldosterone excretion exhibited a more heterogenous histological appearance and were, in terms of ultrastructure, more similar to cells of the zona glomerulosa). Ultrastructurally and immunocytochemically, the clear cells of 21-deoxyaldosterone adenomas showed features of both the zona glomerulosa and the zona fasciculata and are, hence, considered to be hybrid cells. We conclude that the determination of 21-deoxyaldosterone and Kelly's-M1 should be considered in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma has been detected with an imaging procedure.

Adenoma↗
PubMed1994

Clonal composition of human adrenocortical neoplasms.

The mechanisms of tumorigenesis of adrenocortical neoplasms are still not understood. Tumor formation may be the result of spontaneous transformation of adrenocortical cells by somatic mutations. Another factor stimulating adrenocortical cell growth and potentially associated with formation of adrenal adenomas and, less frequently, carcinomas is the chronic elevation of proopiomelanocortin-derived peptides in diseases like ACTH-dependent Cushing's syndrome and congenital adrenal hyperplasia. To further investigate the pathogenesis of adrenocortical neoplasms, we studied the clonal composition of such tumors using X-chromosome inactivation analysis of the highly polymorphic region Xcen-Xp11.4 with the hybridization probe M27 beta, which maps to a variable number of tandem repeats on the X-chromosome. In addition, polymerase chain reaction amplification of a phosphoglycerokinase gene polymorphism was performed. After DNA extraction from tumorous adrenal tissue and normal leukocytes in parallel, the active X-chromosome of each sample was digested with the methylation-sensitive restriction enzyme HpaII. A second digestion with an appropriate restriction enzyme revealed the polymorphism of the region Xcen-Xp11.4 and the phosphoglycerokinase locus. Whereas in normal polyclonal tissue both the paternal and maternal alleles are detected, a monoclonal tumor shows only one of the parental alleles. A total of 21 female patients with adrenal lesions were analyzed; 17 turned out to be heterozygous for at least one of the loci. Our results were as follows: diffuse (n = 4) and nodular (n = 1) adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome, polyclonal pattern; adrenocortical adenomas (n = 8), monoclonal (n = 7), as well as polyclonal (n = 1); adrenal carcinomas (n = 3), monoclonal pattern. One metastasis of an adrenocortical carcinoma showed a pattern most likely due to tumor-associated loss of methylation. In the special case of a patient with bilateral ACTH-independent macronodular hyperplasia, diffuse hyperplastic areas and a small nodule showed a polyclonal pattern, whereas a large nodule was monoclonal. We conclude that most adrenal adenomas and carcinomas are monoclonal, whereas diffuse and nodular adrenal hyperplasias are polyclonal. The clonal composition of ACTH-independent massive macronodular hyperplasia seems to be heterogeneous, consisting of polyclonal and monoclonal areas.

Adenoma↗
PubMed1994

Role of 21-deoxyaldosterone in human hypertension.

21-Deoxyaldosterone has been postulated to be a precursor of aldosterone in an alternative biosynthesis pathway and Kelly's-M1 is considered to be its metabolite. In healthy volunteers, the excretion rate of 21-deoxyaldosterone and of Kelly's-M1 are significantly lower than the aldosterone metabolites, aldosterone-18-glucuronide and tetrahydro-aldosterone and than the aldosterone precursor 18-OH-corticosterone. Essential hypertension patients (with low and normal renin) excrete comparable values of 21-deoxyaldosterone and Kelly's-M1 as normotensives. In 66% of aldosterone-producing adenoma cases (APA) and in 60% of idiopathic hyperaldosteronism (IHA) patients, significantly raised values of 21-deoxyaldosterone and Kelly's-M1 were found. The patients with the high excretion rates of both steroids showed only moderately increased values of the aldosterone metabolites, aldosterone-18-glucuronide and tetrahydro-aldosterone, as well as of the aldosterone precursor 18-OH-corticosterone. In contrast, the latter mentioned steroids were excreted in higher amounts in those patients with normal excretion of 21-deoxyaldosterone and Kelly's-M1. Hence, it is suggested that aldosterone is produced alternatively either via 18-OH-corticosterone alone or additionally via 21-deoxyaldosterone. Furthermore, in three cases of "incidentally" discovered adrenal adenomas, 21-deoxyaldosterone and Kelly's-M1 were the only elevated steroids. After adrenalectomy, excretion of 21-deoxyaldosterone and of Kelly's-M1 and blood pressure returned to normal, which proves that these steroids play a role in blood pressure regulation. In essential hypertension, ACTH infusion induced a significant increase of 21-deoxyaldosterone and Kelly's-M1. However, the increase after angiotensin II was 3- to 6-fold higher than after ACTH. IHA patients proved to be more responsive to angiotensin II; and, in contrast, APA cases proved to be more sensitive to ACTH. The data suggest that beside the main route of aldosterone biosynthesis via 11-deoxycorticosterone, corticosterone and 18-OH-corticosterone an alternative pathway exists via 21-deoxyaldosterone in healthy and in hypertensive patients. There are similarities between the regulation of 21-deoxyaldosterone and the regulation of aldosterone. The determination of 21-deoxyaldosterone and its possible metabolite Kelly's-M1 might be appropriate in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma is discovered.

Adenoma↗
PubMed1992

Low-molecular-weight protein-permeable cuprammonium rayon haemofilter.

Searching for a dialyser membrane with a cut-off similar to that of the human glomerulus, a modified cuprammonium rayon (AM-75-UP) and a polyacrylonitrile (PAN-15-DX) haemofilter were tested in vivo for the ability to eliminate substances of a molecular weight (MW) of 10-65 kilodaltons (kDa). Endogenous marker substances of a defined MW (beta-2-microglobulin 11.8 kDa; retinol binding protein 21 kDa; alpha-1-microglobulin 26.7 kDa; alpha-1-glycoprotein 41 kDa; alpha-1-antitrypsin 54 kDa; albumin 66.3 kDa) were measured by laser nephelometry or immunosorbent assay; sieving coefficients (SC) and protein elimination (PE) per 20 l haemofiltration were calculated for each low-MW protein. The PAN haemofilter shows elimination characteristics comparable to those of earlier tested haemofilters (polysulphone, AN69, cellulose triacetate) with a sharp cut-off in the MW range of 10-15 kDa. The cuprammonium rayon haemofilter is permeable for proteins with a higher MW; especially for alpha-1-microglobulin a relevant removal (SC 0.2; PE 0.56 g/20 l) was established. This membrane has a cut-off more similar to that of the human glomerulus; but far from the demanded quality with a relevant removal of substances in the MW range up to 60 kDa. Calculated albumin loss (2.4 +/- 0.2 g/20 l) seems to be tolerable for stable haemodialysis patients.

Acrylic Resins↗
PubMed1991

Urinary 18,19-dihydroxycorticosterone and 18-hydroxy-19-norcorticosterone excretion in patients with primary and secondary aldosteronism.

18,19-Dihydroxycorticosterone (18,19(OH)2-B) and 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B) measurements were carried out on the urine of patients with primary aldosteronism (PA), essential hypertension (EHT), and liver cirrhosis with (LC, SA (+)) and without (LC, SA (-)) aldosteronism. The separation of these steroids was performed by extraction and high-performance liquid chromatography followed by radioimmunoassay (RIA) with specific antibodies prepared in our laboratory. 18,19(OH)2-B excretion was elevated in patients with PA (24 +/- 5.9 [+/- SE] micrograms/24 hr; n = 15) and LC, SA (+) (83 +/- 9.4 micrograms/24 hr; n = 8). Values in LC, SA (-) (3.1 +/- 1.2 micrograms/24 hr; n = 8) and in EHT (3.7 +/- 0.4 micrograms/24 hr; n = 42) were found to be similar to those in normal subjects (5.5 +/- 0.9 micrograms/24 hr; n = 30). The values of urinary 18-OH-19-nor-B in PA and LC, SA (+) were higher than in LC, SA (-) EHT and normal subjects (P less than 0.05). Values in the latter three groups, as compared with each other, did not show significant alterations. Nothing is known about the biologic relevance of 18,19(OH)2-B and very little about that of 18-OH-19-nor-B, but the latter steroid seems to potentiate experimental renal hypertension. One can speculate about possible roles of both steroids as precursors of other steroids, e.g., the biologically potent mineralocorticoid 19-noraldosterone. The data obtained suggest that it is not relevant to measure the urinary levels of either steroid in these clinical syndromes.

18-Hydroxycorticosterone↗
PubMed1990

Synthesis of 19-nor-aldosterone, 18-hydroxy-19-nor-corticosterone and 18,19-dihydroxycorticosterone in the human aldosterone-producing adenoma.

The recently synthesized 18-C-steroid derivative, 19-nor-aldosterone(19-nor- aldo) and 18-hydroxy-19-nor-corticosterone(18-OH-19-nor-corticosterone) possess mineralocoroticoid and hypertensinogenic activity. They and an additional newly synthesized steriod, 18,19-dihydroxycorticosterone[18,19(OH)2-corticosterone], may play a role in the etiology and pathogenesis of disorders thought to be caused by steroids with mineralocorticoid and hypertensionogenic properties. In this study we provide evidence that 19-nor-aldo, 18-OH-19-nor-corticosterone and 18,19(OH)2-corticosterone are produced in vitro by aldosterone-producing adrenal adenomas and adenomas and adenoma of Cushing's syndrome. "silent" adrenal adenomas and the adjacent adrenal tissue. Measurable amounts of these steroids were found in the incubation fluids of adrenal tissues using specific RIAs performed after a sequence of HPLC systems. The rates of production of the three steroids were high in the aldosterone-producing adrenal adenomas and in adrenal hyperplasia compared with in either Cushing's adenoma or "silent" adenoma.

18-Hydroxycorticosterone↗
PubMed1989

Inappropriate secretion of antidiuretic hormone, polydipsia and hypothalamic calcifications.

We studied a 41 year old patient who had pathologic fluid intake of 10 1/day together with syndrome of inappropriate antidiuretic hormone. Imaging studies revealed a lesion of the anterior wall of the third cerebral ventricle. A review of relevant literature indicated several different disturbances by which alterations of thirst, vasopressin-secretion and abnormalities of anterior third ventricle may be associated. The present case presents an unusual and potentially dangerous combination in this spectrum of changes.

Adult↗
PubMed1989

Allergy to dialysis materials.

One hundred and six unselected patients were screened for allergic symptoms, specific IgE against ethylene oxide (ETO), isocyanates (ISO), formaldehyde (FA), phthalates (PHT), total IgE and eosinophil count. Complement activation was measured during cellulosic dialysis in atopic patients and in a control group. Sixteen patients demonstrated mild allergic symptoms during dialysis treatment. Ten of them had IgE elevation and eosinophilia. Eight of these patients had positive RASTs (ETO: n = 5, ETO-ISO(?)-FA: n = 2, ISO-PHT: n = 1) against dialysis material. All eight had an eosinophilia and seven showed an IgE elevation. An amelioration of symptoms could be obtained in three patients with elevated (greater than 15%) ETO-binding values after switching to ETO-free dialysers; avoiding PHT- and ISO-containing dialysis materials allergic symptoms remained constant. Cuprammonium rayon-induced complement activation had a more rapid onset and was more pronounced in atopic patients. The study confirms the role of ETO, but not of the other dialysis materials in the allergic sensitisation of haemodialysis patients.

Complement Activation↗
PubMed1989

Transmembranous transport and adsorption of beta-2-microglobulin during hemodialysis using polysulfone, polyacrylonitrile, polymethylmethacrylate and cuprammonium rayon membranes.

Beta-2-microglobulin (b2M) was identified as a causative agent of amyloidosis associated with long-term hemodialysis (HD). Therefore, we examined handling of b2M during a 4-hour hemodialysis session. We compared b2M adsoprtion and diffusive/convective elimination between high-flux membranes such as polysulfone (PS; F 60, Fresenius), polyacrylonitrile (AN 69; Filtral, Hospal) and polyacrylonitrile (PAN, PAN 12CX2, Asahi) and less permeable membranes such as cuprammonium rayon (CR; AM 160 H, Asahi) and polymethylmethacrylate (PMMA; BK-1.6 U, Toray). To calculate total elimination, arterio-venous differences of b2M were measured at 0, 5, 20, 60 and 240 minutes; dialysate concentration was analyzed to evaluate diffusive/convective transport. Differences between recovery in dialysate and total removal were regarded as amount removed by adsorption. Total elimination per 4-hour hemodialysis session and per m2 membrane surface was 154.7 +/- 12.3 mg for the PS, 137.8 +/- 28.4 mg for the AN 69, 179.8 +/- 47.5 mg for the PAN, 130.8 +/- 11.8 mg for the PMMA and 14.4 +/- 16.0 mg for the CR membrane. Diffusive/convective transport was 128.0 +/- 18.1 mg for PS, 54.7 +/- 8.1 mg for AN 69 and 106.5 +/- 20.8 mg for PAN and insignificant for PMMA and CR. Adsorption was 26.7 +/- 4.3 mg for PS, 83.1 +/- 29.0 mg for AN 69 and 59.8 +/- 17.2 mg for PAN. Besides transmembranous transport sorption is an important mode of elimination. Weekly endogenous generation rate is about twice as high as b2M elimination.

Acrylic Resins↗
PubMed1988

Urinary excretion of aldosterone metabolite Kelly-M1 in patients with adrenal dysfunction.

Using tetrahydroaldosterone antibody a radioimmunoassay was developed to measure substance Kelly-M1 (K-M1) in human urine. The normal values were lower than observed by Kelly et al. who discovered the catabolite after giving large doses of exogenous aldosterone. While in essential hypertension the excretion of K-M1 was predominantly within the normal range, elevated values were found in most cases of 21-hydroxylase deficiency, both the simple virilizing and salt losing form, primary aldosteronism, renal hypertension and cystinosis. Our findings suggest that K-M1 may be formed from 21-deoxyaldosterone and/or by microbial intervention from aldosterone or its metabolites.

Adrenal Gland Diseases↗
PubMed1988

Beta-2-microglobulin adsorption and release in-vitro: influence of membrane material, osmolality and heparin.

We studied the effects of cuprammonium rayon (CR), polyacrylonitrile (PAN), polysulfone (PS), changes in osmolality, and heparin dosage on beta-2-microglobulin (b2M) handling in an in-vitro model that excluded convective transport and minimized diffusive transport. Both PAN and PS exhibited high adsorption capacity for b2M. Osmolality changes had no effect on b2M adsorption or release. CR membrane adsorption was minimal but increased slightly when higher heparin doses were used. In experiments with CR and high heparin doses (4 U/ml) b2M release occurred during the first 15 minutes of in-vitro dialysis, but this increase was inhibited by removing the leukocytes from the blood, indicating that b2M is released from leukocytes.

Acrylic Resins↗
PubMed1987

[Hypokalemia as the principal symptom of covert vomiting. Clinical and diagnostic aspects].

In ten adults (nine females), referred for hypokalemia as the cardinal symptom of uncertain etiology and normal blood pressure, surreptitious self-induced vomiting was demonstrated as the main cause. In the majority of such patients, the pathognomonic pattern of serum and urine electrolytes (in the unstable phase--loss of gastric juice) allows diagnosis without hospitalization. If there are atypical urinary electrolyte values or the patients deny vomiting, hospitalization or part-hospitalization is recommended, with parenteral administration of 1 litre physiological saline daily under weight control, and (if necessary) toxicological urine tests for diuretics if there is a high urinary chloride level. In this manner a sufficiently accurate diagnosis is possible.

Adolescent↗
PubMed1987

21-Deoxyaldosterone excretion in patients with primary aldosteronism and 21-hydroxylase deficiency.

21-Deoxyaldosterone appears in urine in free and conjugated forms. Total excretion is best determined after acid hydrolysis (pH 1) of urine, followed by extraction, repeated chromatographic purification, and quantitation of the steroid by RIA. 21-Deoxyaldosterone excretion was normal in 70% of patients with essential hypertension (n = 18), while 30% (n = 8) had more or less elevated values. In patients with primary aldosteronism (n = 21) elevated as well as normal values of urinary 21-deoxyaldosterone were found, indicating that in some patients aldosterone may be formed not only from corticosterone but also from the 21-deoxy compound. In patients with 21-hydroxylase deficiency (n = 21) urinary 21-deoxyaldosterone was invariably elevated, whether the patients had the virilizing or salt-losing form of the disease. Although the clinical manifestations of the salt-losing form seem unrelated to the inability to convert 21-deoxyaldosterone to aldosterone, the determination of 21-deoxyaldosterone adds insight into the biosynthesis of aldosterone in primary aldosteronism and 21-hydroxylase deficiency.

Adolescent↗
PubMed1987

Polyacrylonitrile complement activation attenuated by simultaneous ultrafiltration and adsorption.

The highly permeable synthetic polyacrylonitrile (PAN) membrane (Filtral; Hospal, Basle) is regarded as biocompatible for its slight complement activation and leucocyte sequestration. The low C3a and C5a concentrations during PAN dialysis may be due to a lack of complement activation potential of this polymer, but also to elimination of activated complement components by the dialyser through adsorption and/or ultrafiltration (mol wt of C3a and C4a 9000 daltons; of C5a 11,000 daltons). Comparing arteriovenous differences throughout the study, higher concentrations of C3a (+23%; n.s.) and C5a (+80%; P less than 0.05) were measured in the efferent blood lines, suggesting a slight complement activation by the alternate pathway. A significantly lower C4a concentration in the efferent blood lines (-30%, P less than 0.05) indicates an elimination within the dialyser. Significantly higher arteriovenous concentration differences at the beginning of dialysis and increasing sieving coefficients suggest elimination by adsorption, mainly in the first 20 min of haemodialysis. The continuous decrease of C3a and C4a plasma concentrations in the afferent blood line suggests transport across the membrane and removal by the dialysate. Accordingly, measurable amounts of these complement components were detected in ultrafiltrate.

Acrylic Resins↗
PubMed1986

Radioimmunoassay of urinary 21-deoxytetrahydroaldosterone in primary aldosteronism and 21-hydroxylase deficiency.

A radioimmunoassay of 21-deoxytetrahydroaldosterone was developed. Normal daily excretion of the unconjugated metabolite was 1.2 +/- 1.3 micrograms and of the glucuronized metabolite, 11.9 +/- 7 micrograms. The tetrahydroaldosterone/21-deoxytetrahydroaldosterone ratio varied more in patients with primary aldosteronism than in control subjects. Thus, measurements of the urinary excretion of the tetrahydroaldosterone or 21-deoxytetrahydroaldosterone alone did not provide an accurate expression for aldosterone production. Their sum correlated well with the clinical condition, i.e. clear-cut elevation in patients with primary aldosteronism. The diminished tetrahydroaldosterone/21-deoxytetrahydroaldosterone ratio found in patients with 21-hydroxylase deficiency may be attributed to increased bacterial conversion of tetrahydroaldosterone to 21-deoxytetrahydroaldosterone but could also stem from a deficiency implicating zona glomerulosa (aldosterone biosynthesis) regardless of the stage and clinical presentation of the disease.

Adrenal Hyperplasia, Congenital↗