Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects.

The genetic basis of non-syndromic autosomal recessive forms of amelogenesis imperfecta (AI) is unknown. To evaluate five candidate genes for an aetiological role in AI. In this study 20 consanguineous families with AI were identified in whom probands suggested autosomal recessive transmission. Family members were genotyped for genetic markers spanning five candidate genes: AMBN and ENAM (4q13.3), TUFT1 (1q21), MMP20 (11q22.3-q23), and KLK4 (19q13). Genotype data were evaluated to identify homozygosity in affected individuals. Mutational analysis was by genomic sequencing. Homozygosity linkage studies were consistent for localisation of an AI locus in three families to the chromosome 4q region containing the ENAM gene. ENAM sequence analysis in families identified a 2 bp insertion mutation that introduced a premature stop codon in exon 10. All three probands were homozygous for the same g.13185_13186insAG mutation. These probands presented with a generalised hypoplastic AI phenotype and a class II openbite malocclusion. All heterozygous carriers of the g.13185_13186insAG mutation had localised hypoplastic enamel pitting defects, but none had AI or openbite. The phenotype associated with the g.13185_13186insAG ENAM mutation is dose dependent such that ARAI with openbite malocclusion segregates as a recessive trait, and enamel pitting as a dominant trait.

Evidence of a founder effect for four cathepsin C gene mutations in Papillon-Lefèvre syndrome patients.

We describe a mutation and haplotype analysis of Papillon-Lefèvre syndrome probands that provides evidence of a founder effect for four separate cathepsin C mutations. A total of 25 different cathepsin C mutations have been reported in 32 families with Papillon-Lefèvre syndrome (PLS) and associated conditions. A characteristic of these findings is the diversity of different cathepsin C mutations that have been identified. To evaluate the generality of cathepsin C mutations, PLS probands representative of five reportedly unrelated Saudi Arabian families were evaluated by mutational and haplotype analyses. Sequence analysis identified two cathepsin C gene mutations: a novel exon 7 G300D mutation was found in the proband from one family, while probands from four families shared a common R272P mutation in exon 6. The R272P mutation has been previously reported in two other non-Saudi families. The presence of the R272P mutation in probands from these four Saudi families makes this the most frequently reported cathepsin C mutation. To distinguish between the presence of a possible founder effect or a mutational hot spot for the R272P mutation, we performed haplotype analysis using six novel DNA polymorphisms that span a 165 kb interval containing the cathepsin C gene. Results of haplotype analysis for genetic polymorphisms within and flanking the cathepsin C gene are consistent with inheritance of the R272P mutation "identical by descent" from a common ancestor in these four Saudi families. Haplotype analysis of multiple PLS probands homozygous for other cathepsin C mutations (W249X, Q286X, and T153I) also supports inheritance of each of these mutations from common ancestors. These data suggest that four of the more frequently reported cathepsin C mutations have been inherited from common ancestors and provide the first direct evidence for a founder effect for cathepsin C gene mutations in PLS. Identification of these six short tandem repeat polymorphisms that span the cathepsin C gene will permit haplotype analyses to determine other founder haplotypes of cathepsin C mutations in additional PLS families.

Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients.

INTRODUCTION: Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar keratoderma and severe, early onset periodontitis, which results from deficiency of cathepsin C activity secondary to mutations in the cathepsin C gene. To date, 13 different cathepsin C mutations have been reported in PLS patients, all of which are homozygous for a given mutation, reflecting consanguinity. AIM: To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families. METHODS: Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene. RESULTS: The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region. CONCLUSION: Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.

Urinary excretion of sialic acid in patients with superficial bladder tumors.

Urinary total sialic acid/creatinine (TSA/Cr) ratio was determined in 73 patients with superficial bladder tumors and 34 healthy volunteers. The mean TSA/Cr value in the tumor group was higher than the control group (P < 0.001) and this difference was significant. Comparing the urinary TSA/Cr ratio of Tl, Ta, grade I-II, grade III, single, multiple, primary and recurrent tumors, with the control group revealed significant results (P < 0.001). Therefore the urinary TSA/Cr ratio determination in the follow-up of these patients may be used as a non-invasive procedure.

Clinical significance of serum ferritin in patients with renal cell carcinoma.

OBJECTIVES: We examined the serum ferritin levels in 158 patients with renal cell carcinoma and 101 healthy control subjects between 1987 and 1994 to investigate the value of this intracellular protein as a tumor marker. METHODS: Preoperative and postoperative serum ferritin values were analyzed and the patients were stratified to three groups accordingly: group 1, patients with normal values (N-N); group 2, those with preoperative high and postoperative normal (H-N); and group 3, those with preoperative normal or high with postoperative high ferritin levels (H-H). RESULTS: The mean serum ferritin level in 101 healthy control subjects was 85.7 +/- 63.6 ng/mL (range, 3.7 to 265.2). The upper limit of normal, which was calculated by adding 2 standard deviations to the mean was 219.9 ng/mL. Mean serum ferritin in patients with renal cell carcinoma was 274.2 +/- 276.3 ng/mL, which was significantly higher than that of control values (P < 0.01). The sensitivity, specificity, and overall accuracy rate for ferritin increase was 94%, 50%, and 61%, respectively. Multivariate analysis showed that the aforementioned grouping and stage of the disease were the two independent prognostic parameters. Preoperative ferritin levels lost its significance on multivariate analysis. CONCLUSIONS: Our study shows that although serum ferritin was a useful tool in diagnosing and staging patients, it was not ideal in early stages. However serum ferritin seems to be more valuable for follow-up; postoperative values, indeed, predict the prognosis.

Connective tissue growth factor in drug-induced gingival overgrowth.

BACKGROUND: Drug-induced gingival overgrowth is a known side effect of certain chemotherapeutic agents used for the treatment of systemic disorders. The pathogenesis and mechanisms responsible for this condition are not fully understood. This study assesses for the presence and localization of connective tissue growth factor (CTGF) in drug-induced gingival overgrowth tissues. CTGF immunostaining was compared with sections stained with transforming growth factor (TGF)-beta1 and CD31 antibodies in order to investigate possible pathogenic mechanisms. METHODS: Gingival overgrowth samples were obtained from patients undergoing therapy with phenytoin (n = 9), nifedipine (n = 4), cyclosporin A (n = 5), and control tissues from systemically healthy donors (n = 9). Tissue sections were subjected to peroxidase immunohistochemistry and were stained with CTGF and TGF-beta1 polyclonal primary antibodies. Possible relationships between CTGF staining and angiogenesis were also studied using an anti-CD31 antibody as a marker for endothelial cells. Staining was analyzed by computer-assisted quantitative and semiquantitative methodology at 5 defined sites in all samples based on the location of specific landmarks including epithelium and underlying connective tissues. RESULTS: Cellular and extracellular CTGF content in phenytoin gingival overgrowth tissues was significantly (P<0.05) higher compared to the other gingival overgrowth tissues and the controls. Higher CTGF staining in phenytoin gingival overgrowth tissues was accompanied by an increased abundance of fibroblasts and connective tissue fibers. No strong association of CTGF staining with TGF-beta1 or CD31 staining was found. CONCLUSIONS: The data from the present study show significantly higher CTGF staining in phenytoin-induced gingival overgrowth tissues compared to controls, cyclosporin A-, or nifedipine-induced gingival overgrowth. Moreover, semiquantitative analyses of histologic samples support the concept that the phenytoin overgrowth tissues are fibrotic. These associations suggest a possible role for CTGF in promoting development of fibrotic lesions in phenytoin-induced gingival overgrowth.

Ureteropelvic obstruction due to urinary calculi in transplanted kidney.

In chronic renal failure patients many factors may predispose to stone formation following renal transplantation. Urinary calculi occur in transplanted cases in 0.3 to 6.3%. ESWL, percutaneous nephrolithotomy or open surgical treatment is usually necessary to treat these patients. In this study we present a patient transplanted from a living donor at our centre. Stone formation developed 3 months after the operation and ureteropelvic obstruction was corrected by open surgical intervention.

Isolated renal and retroperitoneal hydatid cysts.

Four patients (3 male, 1 female) with isolated renal and 1 female patient with isolated retroperitoneal cysts were reviewed. The mean age of the patients was 46 (25-64). The most common presenting symptom was pain. Two cases were discovered incidentally by the observance of renal calcification on abdominal x-ray. Indirect hemagglutination test was positive in all cases but eosinophilia was present only in 1 (20%) case. Nephrectomy was performed to 1 patient who presented with hydaturia and had a large communicating cyst involving most of the kidney. Total cystectomy was performed in other renal cysts. Total cystectomy with wide excision of the involved muscle was performed to the retroperitoneal hydatid cyst. Patients were followed by an average of 23.8 (9-50) months with indirect hemagglutination test and USG. No evidence for recurrence was found up to date.

Sertoli cell tumor in a prepubertal boy mimicking testicular torsion.

A 9-year-old boy presented with left, intermittent testicular pain that was present for 3 days. On physical examination, left testis was grossly enlarged and firm but mildly tender. Serum alpha-fetoprotein and beta-human chorionic gonadotropin levels were within normal range. Color doppler ultrasonography which was performed to rule out testicular torsion revealed an intratesticular mass located at the upper pole of left testis and left radical orchiectomy was performed. The histopathological diagnosis was Sertoli cell tumor.

Gingival crevicular fluid levels of aspartate amino transferase, sulfide ions and N-benzoyl-DL-arginine-2-naphthylamide in diabetic patients with chronic periodontitis.

BACKGROUND: The aim of this study is to analyze the correlations between plaque index (PlI), gingival index (GI), probable pocket depth (PPD), clinical attachment level (CAL), aspartate aminotransferase (AST), N-benzoyl-DL-arginine-2-naphthylamide (BANA) and sulfide ion activity (SIA) of diabetic patients with chronic periodontitis with regard to disease activity detected by AST levels. MATERIAL AND METHODS: A total of 95 sites from eight diabetic patients with chronic periodontitis and 74 sites from eight systemically healthy patients with chronic periodontitis were enrolled in the study. The patients had no history of periodontal treatment or any antibiotic therapy during the last 6 months and were nonsmokers. All the sites selected for the study had a CAL of at least 2 mm. Gingival crevicular fluid volumes (GCFV) were measured in all sites. RESULTS: According to the result of AST analysis, 45 sites were AST positive and 50 were AST negative in the diabetic group and 36 sites were AST positive and 38 were AST negative in the control group. There was a significant correlation between BANA hydrolysis and PPD in both diabetic and control groups, but no correlation between PPD and AST levels. A significant correlation was observed between AST-positive sites and GI, but not between GI and BANA hydrolysis. In both groups, the correlation between SIA and BANA hydrolysis was significant, but no correlation was revealed between SIA and AST levels in either diabetic or control groups. CONCLUSION: The GCF metabolites had significant correlations with periodontally diseased sites in patients with chronic periodontitis, whether diabetic or systemically healthy, and may help to confirm clinical findings.

A prostaglandin synthesis inhibitor, diclofenac sodium in the treatment of primary nocturnal enuresis.

Various treatment modalities have been used in Primary Nocturnal Enuresis (PNE) and pharmacotherapy is widely accepted. Prostaglandins increase detrusor pressure, decrease urethral pressure and lead to sodium excretion. They also antagonize hydro-osmotic effect of vasopressin by competing with this hormone. According to these functions of prostaglandins it is suggested that inhibition of prostaglandin synthesis may have value in the management of PNE. We evaluated the efficacy or oral diclofenac sodium treatment in 78 patients. We conclude that diclofenac sodium, an inhibitor of prostaglandin synthesis, is a good alternative agent for nocturnal enuresis particularly as a supplementary treatment combined to Imipramine, with 60% complete response and 13.3% recurrence rate.