Botulinum toxin therapy for neurogenic detrusor hyperactivity versus augmentation enterocystoplasty: impact on the quality of life of patients with SCI.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To compare quality of life (QoL) in patients with spinal cord injury (SCI) who underwent overactive detrusor treatment by botulinum toxin (BT) versus augmentation cystoplasty (AC). SETTING: France. METHODS: Prospective and descriptive study: Patients with a refractory overactive bladder due to SCI treated by at least two successive injections of BT or by AC. QoL was assessed using Qualiveen-30 (Q30). Clinical data and urodynamic parameters were collected. RESULTS: Thirty patients were included between March 2013 and March 2014: 14 in arm 1 (BT injections) and 16 in arm 2 (AC). Mean postoperative time after AC was 9.94 years. Mean BT injections already performed was 6.36. Qol was significantly lower in arm 1-Q30 score 1.625 versus arm 2-Q30 score 1.077 (P=0.037). Continence control was significantly higher in arm 2. Fourteen patients were completely continent (87.5%) in arm 2, whereas only 6 (42.3%) were continent in arm 1 (P=0.0187). Urinary infection, reflux, diverticula and stones were almost at a similar occurrence level. CONCLUSIONS: QoL was found to be higher with an AC compared with BT injections. Long-time intervals between two injections and advantages specific to AC might explain in part these findings.

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.

Prevalence of adrenal and extra-adrenal Conn syndrome in hypertensive patients.

BACKGROUND: Primary aldosteronism (PA) is caused by an adrenal aldosterone-producing tumor (A-APT) or adrenal hyperplasia. An extra-adrenal APT (E-APT) as a cause of PA has been reported in 5 cases. Autopsy studies show a high incidence of ectopic adrenocortical tissue. We did a prospective study of the prevalence of A-APTs and E-APTs and the biochemical features of E-APTs in patients with PA. METHODS: Hypertensive patients (N = 3900) referred to our unit were screened for PA by measuring renin activity, urinary aldosterone-18-glucuronide, tetrahydroaldosterone, and 18-hydroxycorticosterone (18-OH-B). Primary aldosteronism was found in 257 cases. The differentiation between A-APTs and adrenal hyperplasia was based on the results of postural response of renin, plasma aldosterone, 18-OH-B, computed tomography, isotope scanning, or adrenal venous aldosterone. Ultrasound examination of the abdomen was used to screen for E-APT. RESULTS: The cause of PA was bilateral adrenal hyperplasia in 101 cases, unilateral adrenal hyperplasia in 2, an A-APT in 146, and an E-APT in 1. The site of aldosterone production was uncertain in 7 patients who had normal adrenal glands on computed tomography but refused to undergo isotopic scanning and adrenal venous catheterization. Ultrasound examination disclosed normal retroperitoneum in 4 of the 7 cases but could not rule out E-APT in 3 cases. The biochemical features of the patient with the E-APT were similar to classic A-APT, with low renin, high aldosterone, and high 18-OH-B values without appropriate response to posture or to short-term volume expansion. The excision of the E-APT in the right kidney resulted in normalization of blood pressure and renin, aldosterone, and 18-OH-B levels. CONCLUSION: Although E-APT is rare, it should be considered in the interests of specific therapy for PA because aldosterone-secreting malignant ovarian tumors also have been reported.

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.

p53 mutations in adrenal tumors: Caucasian patients do not show the exon 4 "hot spot" found in Taiwan.

Mutations in the p53 tumor suppressor gene are frequently present in human cancers but have rarely been described in benign tumors. We previously reported mutations in the "hot spots" between exons 5-8 of the p53 gene in adrenocortical carcinomas but not in adenomas. Recently, a previously unknown hot spot in exon 4 of the p53 gene was described in adrenal adenomas and pheochromocytomas of Taiwanese patients. We, therefore, investigated whether these mutations are also present in Caucasian patients from the U.S. and Europe. We analyzed tumor tissue of 12 aldosterone-producing adenomas, 7 cortisol-producing adenomas, and 6 pheochromocytomas. Overexpression of the p53 protein was investigated by immunohistochemistry. Point mutations within exon 4 were identified by polymerase chain reaction (PCR) amplification and direct sequencing of the PCR product. The pYNZ22 microsatellite located on chromosome 17p, close to the p53 gene, was used to screen for allelic loss (LOH) of the p53 gene. Overexpression of p53 was not identified in any of the adenomas and pheochromocytomas. Point mutations within exon 4 were found in 0/25 tumors. LOH was present in 1/13 informative adenomas and 0/2 informative pheochromocytomas. We conclude that p53 mutations do not play a major role in the tumorigenesis of adrenal adenomas and pheochromocytomas of Caucasian patients. Thus, ethnic and environmental factors may be responsible for the mutational spectrum found in Taiwanese patients.

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.

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.

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.

Characterization of "refilling types" by continuous blood volume monitoring during hemodialysis.

Fluid removal during HD is frequently associated with acute hypotension due to insufficient mobilization of extravascular fluid and subsequent hypovolemia. Large variability in vascular refilling makes dialysis therapy difficult and requires a better understanding of fluid distribution in the individual hemodialysis (HD) patient. Blood volume monitoring was performed by continuous measurement of blood density with a DMA 46 Density Meter (Fa. Chempro, PAAR, Austria) in six patients on regular HD treatment. A body filtration coefficient (CF = extra/intravascular fluid shift) was calculated using a computer model by Schneditz et al (1990) and blood density was measured during a 60-minute ultrafiltration period (1/3 x delta kg/hr = 19 +/- 4 ml/min). Concerning blood density differences (delta f%) and body filtration coefficient (CF) there was a wide inter-individual range (delta f = 2.8-8.0%, CF = 3-9 ml/mm Hg/min), but there was a good intraindividual reproducibility of delta f and CF. A negative correlation (r = -0.95) between delta f and CF could be established. The severity of hypotensive episodes and frequency of interventions correlated well with delta f and CF; severe symptoms occurred with a delta f > 6% and a CF < 4 ml/mm Hg/min. These results suggest that improvement in dialysis therapy can be achieved by blood volume monitoring and classification of "refilling types." By blood volume-controlled computerized sodium and UF profiles, a reduction of hypotensive episodes and emergency intervention might be possible.

Radioimmunoassay of free urinary 18-hydroxydeoxycorticosterone (18-OH-DOC) in patients with essential hypertension.

Specific antiserum was raised in white New Zealand rabbits using 18-hydroxydeoxycorticosterone-3-oxime-BSA complex as antigen. The urinary free 18-OH-DOC was estimated after dichloromethane extraction and separation in one paper chromatographic system (propylene glycol/toluene). The mean 18-OH-DOC excretion value (+/- S.D.) in normal subjects was 0.861 +/- 0.527 microgram/24 h (n=23). ACTH produced a 25-fold increase in the excretion of free 18-OH-DOC. Dexamethasone suppressed the values to the lower range of sensitivity. 32% of patients of essential hypertension showed a moderate increase in the free urinary 18-OH-DOC values. The mean value (+/- S.D.) in the low renin hypertension group was 2.50 +/- 1.49 microgram/24 h (n=19), in the normal renin patient group 1.84 +/- 1.22 microgram/24 h (n=38). The difference between controls and the hypertensive groups was statistically significant. Among the different hypertensive groups significant differences could not be calculated.

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.

[Supra-renal venography in patients with suspected endocrine hypertension (author's transl)]. / Nebennierenvenographie bei Patienten mit Verdacht auf endokrine Hypertonie

In forty patients suspected clinically of having an endocrine cause for hypertension, an adrenal cortical adenoma was confirmed histologically in five. Hyperaldosteronism with enlarged or normal adrenals was demonstrated in three patients. The diagnosis in a further eight patients with an abnormal hormone pattern and/or an abnormal venogram has not yet been confirmed. Adrenal glands show considerable variation in their size, shape and localisation on venography.

Three cases of hemodialysis-associated hypersensitivity reactions.

According to the United States Food and Drug Administration, untoward reactions to capillary hemodialyzers occur at a rate of 3.5 of every 100,000 dialyzers sold. Allergic symptoms immediately after initiation of dialysis consist of burning retrosternal pain, sensation of diffuse heat, cold perspiration, periorbital and facial edema, flushing, laryngeal stridor, bronchial hypersecretion, hypotension, bradycardia, and loss of consciousness. In 1982 Popli et al. reported four patients suffering from such allergic manifestations; three were successfully managed after being taken off dialysis. These investigators thought that inadequate rinsing of cuprammonium cellulose capillary dialyzers was responsible for the reactions, and recommended rinsing the blood compartment with 2 liters of normal saline, and the dialysate compartment with 10 liters of dialysate, both in a single-pass fashion over 20 minutes. Nichols and Platts (1982) (3) reported 15 patients with urticaria, severe bronchospasm, and shock occurring immediately after the blood had been returned from the dialyzer. These authors suggested that the sterilizing agent, ethylene oxide (ETO), was responsible. Poothullil et al. (1975) (4) described a patient with pruritus, severe dyspnea, and hypotension during dialysis. On the basis of a positive skin prick test (dermal reaction to ETO-exposed human albumin) and of antigen-induced histamine release from peripheral leucocytes, these workers suggested that ETO was responsible for the allergic reactions. Marshall et al. (1984) (5) reported that 8.9% of hemodialysis patients had positive skin tests to ETO and that 12.1% were ETO-radioallergosorbent test (RAST) positive.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

[Stauffer syndrome, paraneoplastic hepatic dysfunction syndrome associated with renal cell carcinoma (author's transl)]. / Das Stauffer-Syndrom, Beitrag zum paraneoplastischen Leberdysfunktionssyndrom bei Nierenzellkarzinomen

In two patients with renal cell carcinoma, the following biochemical changes were found independently of hepatic metastases: increased alkaline phosphatase activity, rise in bromsulfothalein retention, hypoalbuminemia, increase in alpha2-globulin, and prolonged prothrombin time (Stauffer syndrome). In both cases the syndrome was found to be the first sign of the renal cell carcinoma. In one patient liver function returned to normal after removal of the neoplasm, in correlation with the good recovery. In the other case the abnormal laboratory findings persisted after total renal surgery. Clinically, diffuse pulmonary metastases occurred. Both case histories show the high significance in knowing Stauffer syndrome and its value for early diagnosis and operative success.

Pseudo-bartter syndrome, pattern and correlation with other cystic fibrosis features.

Pseudo-Bartter Syndrome (PBS), although quite common in patients with cystic fibrosis (CF), is often missed as simple dehydration or Bartter syndrome. This study was performed in patients with PBS to compare the pattern and course of the disease with those with CF not manifesting with this syndrome. All patients with CF who attended the respiratory clinic at Queen Rania Al-Abdallah Hospital from January 2000 to April 2010 were included in this retrospective case-control study. A specially formulated data sheet was used and those with PBS and those not having the syndrome were identified. A total of 110 patients (51% female) with CF with a median age of seven years were followed-up. Eighteen (16.3%) of them had one or more episodes of PBS. The median follow-up period was 6.2 years. All the episodes occurred during summer and in infancy. Median age of the initial episode of PBS was three months. One-third of them were initially followed at the nephrology clinic. Three patterns of PBS were identified: single episode in three (16.6%) patients, recurrent in 12 (66.6%) patients and chronic in three (16.6%) patients. Early colonization of Pseudomonas spp before 1 st birthday was seen in 44% patients with PBS compared with 12% in other CF patients (P-value = 0.0075). The total number of colonized patients and other CF features at the time of the study did not differ significantly among patients, although the mean Shwachman-Kulczycki score is significantly lower in those with recurrent PBS (69 compared with 85 in other CF patients). Gene mutation was identified in only 30% of the entire cohort. PBS is common in patients with CF, and it should be kept in mind in any patient with hypotonic dehydration and metabolic alkalosis. Recurrent pattern is associated with earlier Pseudomonas colonization.

Multicentric epithelioid hemangioendothelioma involving the lungs, trachea, liver and skeletal muscles.

Epithelioid hemangioendothelioma (EH) is a rare benign vascular tumor, which typically present as multinodular lesions that can involve one organ or more. We report a 12 years old female who presented with one-year history of progressive intolerance to physical activity and 3 months history of dry cough and weight loss. Physical examination was positive for diminished breath sounds and crackles of right hemithorax, and small mass in abdominal wall. CT of chest and abdomen revealed multiple nodular lesions in both lungs, liver, and right abdominal rectal muscle. Bronchoscopy showed multiple small tracheal lesions. Immunhistochemical staining of biopsy specimens obtained from the trachea, liver and muscle was consistent with EH.

Bronchoscopy findings in children with recurrent and chronic stridor.

BACKGROUND: To describe the bronchoscopic findings and treatment decision of children with chronic or recurrent stridor referred to the pediatric respiratory clinic at Queen Rania Hospital for Children. METHODS: All children who underwent flexible bronchoscopy at the pediatric bronchoscopy unit for chronic stridor from January 2009 to January 2010 were included. Stridor was divided into 3 groups: inspiratory, expiratory, or biphasic. All patients from 2 weeks of age till 14 years were included. Files of these patients were retrospectively reviewed. A specially formulated data sheet including clinical history and physical findings, type of stridor, bronchoscopic findings, and management decision was used. Radiologic investigation results were included when relevant. Flexible bronchoscopy was performed under sedation and topical anesthesia. RESULTS: A total of 64 children [35 (54.7%) male and 29 (45.3%) female] were included. Twenty-four patients had inspiratory stridor. There were 33 patients with biphasic stridor (subglottic stenosis in 9, paradoxical vocal cord movement in 6, vascular ring in 5, subglottic hemangioma in 3, vocal cord paralyses in 4, foreign body in 2, laryngeal web in 2, and absent vocal cord and tracheal bronchus in 1 each). Seven children had expiratory stridor. Of patients with laryngomalacia, 50% had associated tracheomalacia and 70% of those with laryngomalacia and all patients with tracheomalacia had associated gastroesophageal reflux. Two patients with paradoxical vocal cord movement were found to have Arnold-Chiari malformation. All patients with vascular rings underwent surgery. CONCLUSION: Flexible bronchoscopy should be performed in all patients with chronic or recurrent stridor to assess the airway and guide further investigations and management.

Clinical profile of cystic fibrosis. Atypical presentation.

OBJECTIVE: To describe the unusual presentation among patients with confirmed cystic fibrosis. METHODS: A retrospective review was carried out on all children (n=90) with the diagnosis of classical cystic fibrosis who attended the Respiratory Pediatric Clinic at King Hussein Medical Center, Amman, Jordan from January 2002--December 2008. All children from one day old to 14 years of age were included. Files of those with unusual presentation were reviewed. Age at presentation and diagnosis, clinical presentation, and family history were collected. Relevant laboratory results, sweat chloride readings, and radiological features were also reviewed. RESULTS: Ninety children (males 51 [57%] and females 39 [43%]) with classic cystic fibrosis were included. The most common initial classical presenting manifestation was recurrent wheezy chest (24%). The least common presentation was direct hyperbirubinemia (3%). Seven cases (8%) had unusual clinical presentations: early pulmonary hypertension, non-obstructive left hydronephrosis with metabolic alkalosis, single isolated episode of metabolic alkalosis, severe iron deficiency anemia with short stature, and the finding of ichthyotic skin lesions. Three of these patients had a positive family history of cystic fibrosis. Two patients with pulmonary hypertension died. The overall mortality rate was 4%. CONCLUSION: The wide variability of clinical presentations reflects the diversity of clinical picture of cystic fibrosis as a disease. Neonatal screening programs at a national level can decrease the burden of the disease.