Familial Mondini dysplasia

OBJECTIVES/HYPOTHESIS: To determine the mode of inheritance of familial nonsyndromic Mondini dysplasia. Study Design: Correlative clinical genetic analysis of a single kindred. METHODS: Clinical history, physical examination, audiologic analysis, computed tomography of the temporal bones, and cytogenetic analysis. RESULTS: The male proband, three affected sisters, and an affected brother are offspring of unaffected parents. The mother and an unaffected brother have audiologic findings suggestive of heterozygous carrier status for a recessive hearing loss gene. CONCLUSIONS: Pedigree analysis indicates autosomal recessive inheritance in this family. The observed inheritance and clinical, audiologic, and radiologic findings are different from those previously described for another family with nonsyndromic Mondini dysplasia. The phenotype in this study family therefore represents a distinct subtype, indicating clinical and genetic heterogeneity of this disorder. This information should facilitate future molecular linkage analyses and genetic counselling of patients with inner ear malformations.     

Fibromuscular dysplasia of the renal arteries

Thirty-two cases of fibrous-muscular dysplasial of renal arteries (including one autopsy case) were studied. Sections of renal arteries removed at reconstructive operations from patients suffering from renovascular hypertension were examined. Two morphological variants of the process were distinguished: medial dysplasia (perimedial fibroplasia, medial fibroplasia, and dissecting aneurysm) and intimal proliferation. Morphologically, fibrous-muscular dysplasia is a manifestation of proliferation of smooth muscle cell which appears to have various forms and stages. Diagnostically, fibrous-muscular dysplasia should be differentiated from atherosclerosis, nonspecific arteritis, proliferation of the intima due to hypovolemia, and perivascular sclerosis of different etiologies.     

Familial clustering of end-stage renal disease in blacks with lupus nephritis

The factors that determine a patient's susceptibility to specific target organ involvement in systemic lupus erythematosus (SLE) remain unknown. Lupus nephritis can be a particularly devastating complication, with an increased mortality and the risk of progressive renal damage resulting in end-stage renal disease (ESRD). This analysis was performed to determine whether renal disease aggregated in select families or was a sporadic complication in patients with SLE. We compared the family history of ESRD in 50 patients with SLE complicated by lupus nephritis with 37 controls who had SLE but lacked nephritis after a mean follow-up duration of more than 11 years. The frequency of relatives with ESRD in the lupus nephritis cases was compared with that in controls using Fisher's exact test (significance at P < or = 0.05). Fifty percent (25) of the 50 lupus nephritis patients were black and 50% (25) white, in contrast to 35% (13) and 65% (24) of the 37 lupus non-nephropathy controls, respectively. A first-, second-, or third-degree relative with ESRD was present in 16% (eight) of the 50 lupus nephritis cases and in 0% of the 37 SLE non-nephropathy controls (P = 0.019, Fisher's exact test, two-tail). Twenty-eight percent (seven) of the 25 black patients with lupus nephritis had relatives with ESRD compared with 0% of the 13 black lupus non-nephritis controls (P = 0.07). Only one of the eight relatives with ESRD had SLE or a collagen vascular disease. Lupus nephritis patients and the non-nephritis controls had similar ages (mean +/- SD: 38.5 +/- 10.0 years v 46.6 +/- 11.8 years; P = 0.28), family sizes (6.27 +/- 2.61 first-degree relatives v 6.35 +/- 3.25 first-degree relatives; P = 0.16), and duration of SLE (9.26 +/- 5.94 years v 11.35 +/- 6.43 years; P = 0.60). Familial clustering of ESRD was observed in black patients with SLE who had nephritis. This was unlikely to be related to differences in patient age, family size, or duration of SLE. This data, coupled with the known familial aggregation of ESRD in blacks with hypertensive and diabetic ESRD, supports the contention that genetic factors contribute to the familial clustering. The presence of relatives with etiologies of ESRD other than SLE suggests that there is an inherited susceptibility to progressive renal failure, independent of the etiology of ESRD.     

Familial granulomatous arthritis (Blau syndrome) with granulomatous renal lesions

PURPOSE: To identify the BIGH3 gene mutation in 10 unrelated Japanese individuals with granular corneal dystrophy. METHODS: Genomic DNA was obtained from each patient's leukocytes. Exons 4 and 12 of the BIGH3 gene were amplified by polymerase chain reaction and were directly sequenced. RESULTS: Nine of these patients were found to have the R124H mutation, whereas only one had the R555W mutation. Slit-lamp examination showed that the granular corneal dystrophy associated with each mutation is different. CONCLUSIONS: These results, together with our previous findings, show that the classic form of granular corneal dystrophy associated with the R555W mutation is rare in Japanese patients, whereas granular corneal dystrophy accompanied by amyloid deposits and associated with the R124H mutation, Avellino corneal dystrophy, is more common. Direct examination may be insufficient in the proper diagnosis of corneal dystrophy, and BIGH3 mutation analysis may be required.     

Medullary renal dysplasia mimicking renal tumor in the Beckwith-Wiedemann syndrome

The known association of Wilms' tumor with the Beckwith-Wiedemann syndrome has prompted a surveillance regimen for children with this problem. Herein we report a case of medullary renal dysplasia that was a new onset by documented ultrasound. The association of medullary renal dysplasia with Beckwith-Wiedemann syndrome is discussed as well as the management of this problem.     

Late presentation of solitary jejunal metastasis from renal cell carcinoma

Haematogenous metastases to the small bowel are a rare occurrence, usually from malignant melanoma or bronchogenic carcinoma. There are occasional reports of other primary tumours presenting with small bowel involvement as the first evidence of metastases. We describe a case of intraluminal jejunal metastasis from a renal cell carcinoma, occurring 10 years after the original nephrectomy.     

Genetic study of renal artery fibromuscular dysplasia

The aim of this study was to conduct a formal pedigree analysis of the involvement of the elastin gene in families. From 140 subjects with renal FMD documented on angiography, family cases with documented renal artery fibromuscular dysplasia (FMD) and to test pedigrees were constructed and familial cases defined by angiographic evidence of FMD in at least one sibling. Familial screening was made either by echodoppler for asymptomatic subjects or by digital intravenous angiography for hypertensive subjects. Linkage analysis at the elastin gene locus was performed in these families with two polymorphic markers: one diallelic RFLP located in exon 16 and one multiallelic CA repeat located in intron 17 of the elastin gene. Fourteen pedigrees (10%) were obtained including nine sibling pairs, four trios and one vertical transmission from a father to his daughter. Most affected subjects were females (84%) but familial cases were more frequently bilateral than sporadic cases (80% vs 49%, p = 0.07). Pedigrees analysis was compatible with an autosomal dominant mode of inheritance and suggested in these families an age and sex-dependent incomplete penetrance model. Linkage analysis resulted in a maximum two-point lod score of 0.06 at theta = 0.20 using the dinucleotide CA repeat. Analysis of the diallelic marker revealed similar frequencies in affected and non affected subjects. This study highlights the role of genetics factors in approximately 10% of FMD cases. The elastin gene does not seem to be involved in the pathogenesis of FMD.     

Familial renal disease or familial juvenile hyperuricaemic nephropathy?

PURPOSE: To investigate the difference of pharmacokinetics of thiol-containing drugs in various disease states, we studies the covalent binding of SA3786, a bucillamine derivative, with proteins in patient serum compared with that in healthy serum. METHODS: Sera from healthy volunteers and patients of various diseases were supplied by the Japanese Red Cross Kumamoto Hospital. For the formation of conjugate experiments, SA3786 was added to a final concentration of 7 x 10(-4)M. After 6 h incubation at 37 degrees C, HPLC analysis of 5 microliters aliquots of each sample was performed using a column of N-methylpyridinium polymer (4VP-Me). RESULTS: The extent of HSA-SA3786 conjugate formation was found to be lower in the sera from healthy volunteers (control) than those from patients of various diseases. Especially high reactivity with SA3786 was observed in sera from rheumatic patients and hepatic patients. With the exception of the fraction of mercaptoalbumin (fHMA), none of the parameters showed a good correlation with conjugate formation. CONCLUSIONS: The parameter fHMA must be considered to be one of the most important factors in formation of conjugates between plasma protein and thiol compounds. However, other factors may be involved in addition to fHMA although the nature of these factors is not clear.     

Clinical features of unilateral multicystic renal dysplasia in children

Several recent studies have investigated the effectiveness of various behavioral interventions on the cognitive performance of subjects with Alzheimer's disease (AD). Simulations of Shaw's structured model of the cortex led to the predictions that music might enhance spatial-temporal reasoning. A subsequent behavioral study in college students documented an improvement in scores on a spatial-temporal task after listening to a Mozart piano sonata. In this study, we investigated the enhancement of scores on a spatial-temporal task after a Mozart listening condition in a set of twins who are discordant for AD. After listening to an excerpt from a Mozart piano sonata, the AD twin showed considerable improvement on the spatial-temporal task when compared with pretest scores. Furthermore, no enhancement of scores was seen following either of the control conditions (i.e., silence or 1930s popular tunes). This finding suggests that music may be used as a tool to investigate functional plasticity in Alzheimer's disease and to better understand the underlying pathophysiology.     

Distal ureteral atresia associated with crossed renal ectopia with fusion: recovery of renal function after release of a 10-year ureteral obstruction

We report on a 10-year-old boy with distal ureteral atresia associated with crossed renal ectopia with fusion. He was admitted with a high fever associated with a urinary tract infection. The diagnosis was established by antegrade and retrograde pyelography. The upper hydronephrotic portion of the kidney, obstructed for 10 years, recovered its function after nephrostomy placement. To our knowledge, this is the first patient whose renal function has recovered despite an ureteral obstruction of 10-years' duration. Therefore, we recommend a transient nephrostomy placement even for far advanced pediatric hydronephrosis, to test for the possibility of functional recovery.     

Fibromuscular dysplasia of the renal arteries associated with antiphospholipid autoantibodies: two case reports

A relationship appears to exist between antiphospholipid autoantibodies (APLA) and vascular occlusion, although the exact mechanism is still a matter of debate. We present and comment on two cases of renal artery occlusion in patients with concomitant presence of arterial fibromuscular dysplasia and high APLA titers.     

Familial cryptogenic fibrosing pleuritis with Fanconi's syndrome (renal tubular acidosis). A new syndrome

We describe two siblings with a progressive unrelenting and unique syndrome of bilateral fibrosing pleuritis of unknown cause occurring in association with Fanconi's syndrome (renal tubular acidosis). The parents of the siblings were second cousins. Both siblings had identical pleural histologic characteristics and identical urinary metabolic defects. This condition resulted in the development of severe respiratory failure in both patients and ultimately the death of the older sibling at the age of 21 years.     

Characterization of fetal ovine renal dysplasia after mid-gestation ureteral obstruction

OBJECTIVE: The etiology and pathogenesis of renal dysplasia are poorly understood. To characterize the histologic changes in fetal renal dysplasia, we studied a fetal ovine model of urinary obstruction. DESIGN: Animal study. ANIMALS: Seven fetal lambs, and other lambs of the same gestational age as controls. INTERVENTIONS: Unilateral ureteral ligation on fetal lambs at approximately 70 days' gestation (term for sheep is 145 days), during nephrogenesis. Kidneys were subsequently collected, examined histologically and characterized by immunohistochemical tests involving cytokeratin antiserum and a monoclonal antibody to alpha-actin. OUTCOME MEASURES: Histologic changes in ligated fetal lamb kidneys, based on comparison with normal fetal lamb kidneys. RESULTS: At near term (140 days' gestation), the ligated kidney showed distorted and less abundant renal parenchyma than a normal control kidney. Upon microscopic examination, the ligated kidney displayed marked architectural distortion of the outer cortex, with abundant interstitial fibrosis, primitive ductules and glomeruli, and cysts of varying sizes lined by squamous and cuboidal epithelia and surrounded by a loose mesenchyme. The renal medulla contained differentiated collecting ducts, which were structurally distorted and less abundant than in normal control kidneys. The proximal and distal tubule elements were primitive and markedly underdeveloped. Cytokeratin immunoreactivity was present in the collecting duct epithelium and in the cuboidal epithelium lining many of the cortical cysts. Smooth muscle alpha-actin immunoreactivity was localized in the cortical region of the kidney, which highlighted the abundance and disorganization of the undifferentiated mesenchyme and identified the fibromuscular collars of the primitive ductules of the cortex and the distorted collecting ducts of the medulla. CONCLUSIONS: These results highlight the histologic changes resulting from unilateral ureteral ligation in fetal lambs. This model is useful in the study of the pathogenesis of fetal obstructive renal dysplasia.     

Small-bowel necrosis associated with jejunal tube feeding

OBJECTIVE: This paper reports the results of a prospective randomized double-blind trial on the effects of pre-operative clonidine on platelet aggregation. METHODS: Thirty adult (ASA I-II) patients undergoing elective minor orthopaedic surgery were randomly allocated into three groups of ten patients each. In group I clonidine 2 microg x kg(-1), in group II clonidine 4 microg x kg(-1) and in group III saline placebo was administered intravenously before the induction of anaesthesia. Anaesthesia was induced with propofol and vecuronium and maintained with halothane-nitrous oxide. Platelet counts and aggregation tests were performed before (t0) and 1 h (t1) and 24 h (t24) after administration of the study drug. RESULTS: Changes in platelet counts among the groups and values over time were not significant. Both maximum rate and intensity of collagen-induced aggregation in both clonidine groups and maximum intensity of adenosine 5'-diphosphate (ADP)-induced aggregation in the high-dose clonidine group increased significantly at t1. However, all these increases in aggregation were within the normal ranges. CONCLUSION: The effects of both low and high doses of clonidine on platelet aggregation appeared to be minor, and we did not observe any increases above the normal ranges.     

Partial renal embolization for pediatric renovascular hypertension secondary to fibromuscular dysplasia

We report a 7-year-old boy with renovascular hypertension showing multiple stenoses and microaneurysms of the dorsal branch of the left renal artery caused by fibromuscular dysplasia. Hypertension was successfully treated with transcatheter alcohol and gelatin sponge embolization of the dorsal branch and its distribution. The vertebral branch remained intact. No severe complication was encountered. Loss of renal function by renal scintigraphy was minimal. The patient remains asymptomatic at 1 year.     

Cardiovascular malformations associated with choanal atresia

In this study, cardiovascular malformations were present in 11 of 63 (17.5%) patients with choanal atresia. The most frequently encountered cardiac lesions were ventricular septal defect and patent ductus arteriosus, while cyanotic heart disease was uncommon.