N-acetyl transferase 2 polymorphism and advanced stages of endometriosis in South Indian women

Aylamine-N-acetyl transferase is a phase II detoxification enzyme encoded by the gene NAT2. Single nucleotide polymorphism (SNP) changes from the wild type NAT2 *4 allele result in allelic variants *5, *6 and *7. Homozygotes for the NAT2 *4 wild type are fast acetylators; heterozygotes with one wild-type allele and a variant NAT2 *5, *6 or *7 allele have reduced enzyme activity and individuals with two variant alleles are slow acetylators. Previous studies have implicated NAT2 as a susceptibility factor in endometriosis. This study investigated the NAT2 allele frequencies and genotype distributions in 252 unrelated women with endometriosis and 264 controls of South Indian origin. No differences were found between the frequencies of fast and slow acetylators in cases (34.9% and 65.1%) and controls (33.3% and 66.7%). Two NAT2 genotypes *7/*7 (1.2%) and *5/*6/*7 (1.6%) were detected in endometriosis cases only. Four new combinations, 6D (481 + 590 mutation), 7C (590 + 857), 7D (590 + 803 + 857) and 7E (481 + 590 + 803 + 857) were detected, which have not been reported earlier. Similar genotype and phenotype results were obtained in 33 affected sister-pairs. The case-control data from this study suggest there is no association between endometriosis and NAT2 in South Indian women; however, two new variant genotypes and seven SNP combinations were also identified in cases only, which suggests that the gene may still have some as yet undetermined role in the disease.     

Pseudohypoparathyroidism presenting with bony deformities resembling rickets

Pseudohypoparathyroidism (PHP), characterized by hypocalcemia, hyperphosphatemia and elevated parathormone level, may rarely be associated with bony deformities resembling rickets. The authors report two siblings with clinical and radiological features suggestive of rickets unresponsive to treatment with vitamin D. Low serum calcium, elevated serum phosphate, normal renal functions, raised tubular maximum of phosphate and high serum parathormone were suggestive of PHP. Treatment with 1-hydroxyvitamin D and calcium carbonate led to decrease in bone pain, increase in height and weight and resolution of radiological features. PHP should be suspected in patients with bony deformities, hypocalcemia, elevated blood phosphate levels and normal renal functions.     

Idiopathic granulomatous hepatitis

A 12-year-old male child reported with history of fever for last seven years. Hepatosplenomegaly, hepatic and bone marrow granulomas were the main features. Idiopathic Granulomatous Hepatitis (IGH), a rare syndrome amenable to immunosuppressive therapy was diagnosed.     

Long-term effects of cerebellar retraction in the microsurgical resection of vestibular schwannomas

OBJECTIVE: To determine the long-term effects, if any, of the greater cerebellar retraction that is required for retrosigmoid vestibular schwannoma versus resection as compared with the minimal, if any, cerebellar retraction required for translabyrinthine versus resection. STUDY DESIGN: Retrospective case control. METHODS: All patients who underwent retrosigmoid versus resection between 1988 to 2000 by one surgeon were identified. These patients were contacted and asked to complete the Dizziness Handicap Inventory (DHI). These patients were then matched to patients who underwent translabyrinthine versus resection according to age at surgery, age at time of study, sex, and size of tumor. Total DHI and subcategory DHI scores were compared using the Student t test. RESULTS: Thirty-three patients underwent the retrosigmoid approach, and 27 were contacted for completion of the survey, with a 81.3% response rate. Forty-six patients who underwent translabyrinthine versus resection were matched to the retrosigmoid group. Thirty-six were contacted and completed the survey for a 75% response rate. Twenty-seven patients that most closely matched the retrosigmoid group comprised the translabyrinthine group used for comparison. Minimal differences were seen between the two groups. Mean total DHI score for the retrosigmoid group was 17.6, which was not significantly different from the mean score of 16.8 seen in the translabyrinthine group (P =.888). When comparing small tumors (<1.5 cm), total DHI scores were not found to be significantly different (P =.859). We observed similar findings in those with intermediate-sized tumors (1.5-3 cm). CONCLUSION: The significantly greater cerebellar retraction that is necessary for retrosigmoid versus resection does not result in greater long-term balance and disability as compared with those patients who have undergone the translabyrinthine approach.     

Teflon-induced granuloma: a source of false positive positron emission tomography and computerized tomography interpretation

Patients diagnosed with malignancy often undergo combined positron emission tomography (PET) and computerized tomography (CT) to investigate possible metastases. This report presents a case in which, in the investigation of suspected pulmonary malignancy, combined PET and CT images suggested a malignant lesion at the level of the vocal fold. Biopsy of the lesion, however, confirmed the clinical diagnosis of a Teflon granuloma. The case highlights the potential for a false positive report during scanning of patients who have had vocal fold injection.     

Characterization of a first-pass gradient-echo spin-echo method to predict brain tumor grade and angiogenesis

BACKGROUND AND PURPOSE: No widespread clinical method provides specific information about the angiogenic characteristics of gliomas. We characterized blood volume and vascular morphologic parameters from combined gradient-echo (GE) and spin-echo (SE) MR imaging and assessed their relationship to tumor grade, a known correlate of glioma angiogenesis. METHODS: Simultaneous GE and SE echo-planar imaging was performed with bolus gadolinium administration (0.20-0.25 mmol/kg) in 73 patients with glioma. To diminish possible T1 changes due to contrast agent extravasation, a preload (0.05-0.10 mmol/kg) was administered before the study, and a postprocessing correction algorithm was applied. Image maps of total (GE) and microvascular (SE) relative cerebral blood volume (rCBV) and the mean vessel diameter (mVD) calculated from the ratio of GE and SE relaxation rate changes (DeltaR2*/DeltaR2) were compared with tumor grade. A nonparametric K nearest-neighbor decision rule was applied to determine if the combined data could be used to distinguish low-grade (I-II) from high-grade (III-IV) tumors on a per-patient basis. RESULTS: For whole tumors, significant correlations were found between GE rCBV and grade (P < .0001) and between mVD and grade (P = .0001) but not between SE rCBV and grade (P = .08). For areas of highest SE rCBV (microvascular hotspots), SE rCBV and tumor grade were significantly correlated (P = .0007). In terms of differentiation, 69% of low-grade tumors and 96% of high-grade tumors were correctly classified. CONCLUSION: Combined GE and SE MR imaging provides information consistent with neoplastic angiogenesis, demonstrating its potential to aid in optimizing treatments, categorizing lesions, and influencing patient care.     

Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome

Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant NS (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes of ESRD in the first two decades of life. Mutations in the NPHS2 gene represent a frequent cause of SRNS, occurring in approximately 20 to 30% of sporadic cases of SRNS. On the basis of a very small number of patients, it was suspected that children with homozygous or compound heterozygous mutations in NPHS2 might exhibit primary steroid resistance and a decreased risk of FSGS recurrence after kidney transplantation. To test this hypothesis, NPHS2 mutational analysis was performed with direct sequencing for 190 patients with SRNS from 165 different families and, as a control sample, 124 patients with steroid-sensitive NS from 120 families. Homozygous or compound heterozygous mutations in NPHS2 were detected for 43 of 165 SRNS families (26%). Conversely, no homozygous or compound heterozygous mutations in NPHS2 were observed for the 120 steroid-sensitive NS families. Recurrence of FSGS in a renal transplant was noted for seven of 20 patients with SRNS (35%) without NPHS2 mutations, whereas it occurred for only two of 24 patients with SRNS (8%) with homozygous or compound heterozygous mutations in NPHS2. None of 29 patients with homozygous or compound heterozygous mutations in NPHS2 who were treated with cyclosporine A or cyclophosphamide demonstrated complete remission of NS. It was concluded that patients with SRNS with homozygous or compound heterozygous mutations in NPHS2 do not respond to standard steroid treatment and have a reduced risk for recurrence of FSGS in a renal transplant. Because these findings might affect the treatment plan for childhood SRNS, it might be advisable to perform mutational analysis of NPHS2, if the patient consents, in parallel with the start of the first course of standard steroid therapy.     

Is addition of a third or fourth antiglaucoma medication effective?

PURPOSE: To study the intraocular pressure (IOP)-lowering effect of adding a third or a fourth antiglaucoma medication to preexisting antiglaucoma medical therapy, for a follow-up period of one year. PATIENTS AND METHODS: The authors performed a retrospective, nonrandomized, noncomparative, interventional study including all patients seen by a single glaucoma specialist at the University of Florida Eye Clinic between January 1, 2000 and December 31, 2000, who had a third or a fourth antiglaucoma medication added to their existing regimen of two or three antiglaucoma medications, respectively. The main outcome measured was IOP at 2, 6, 9, and 12 months after addition of an antiglaucoma medication. "Efficacy" success was defined as a decrease in intraocular pressure of greater than or equal to 20% from baseline, without a change in the antiglaucoma medical therapy. Also, "safety outcome" was analyzed based on the need for surgical intervention and/or the occurrence of intolerable side effects to the antiglaucoma medications leading to discontinuation of their use. RESULTS: Sixty-seven patients had a third, and 29 patients had a fourth antiglaucoma medication added to their existing regimen. Analysis for a specific time point showed a success rate of 48% at 2 months (n = 65), 47% at 6 months (n = 47), and 41% at 1 year (n = 39) after addition of a third antiglaucoma medication and 59% at 2 months (n = 29), 45% at 6 months (n = 22), and 55% at 1 year (n = 20) after addition of a fourth antiglaucoma medication. By Kaplan-Meier analysis the cumulative probability of achieving efficacy success (> or = 20% IOP decrease from baseline) was 33% at 6 months and 23% at 1 year after adding a third medication (Group A), and 43% at 6 months and 18% at 1 year after adding a fourth medication (Group B). Combining both efficacy and safety outcomes decreased the cumulative probability of success to 27% and 14% in Group A, and 31% and 14% for Group B, at 6 months and 1 year respectively. CONCLUSION: Addition of a third and fourth antiglaucoma medication produces a clinically significant reduction in IOP in about 40 to 60% of patients at any single time point. However, the cumulative probability of success including safety outcomes is relatively poor at 6 months and 1 year. This suggests that adding another antiglaucoma medication to a regimen of two or three medications frequently does not achieve a significant (> or = 20%) fall in IOP.