Debate: the key to stone formation is ...
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Animals↗
Biomedical subjects
P N Rao
Publications and source records attributed to P N Rao.
Duplication 8q22.1-q24.1 associated with bipolar disorder and speech delay.
OBJECTIVE: To report a case of a child with bipolar disorder found to have an unbalanced translocation involving the long arm of chromosome 8, a region that has been previously implicated in genome-wide linkage scans. CASE REPORT: A 7-year-old boy with a complex psychiatric symptom presentation including attention deficits, distractibility, impulsivity, pressured speech, sleep disturbance, aggressive behavior, and hypersexuality diagnosed with bipolar disorder. He also showed evidence of borderline intellectual and adaptive functioning and had mild dysmorphic features with a duplication of distal 8q that arose as an unbalanced chromosomal translocation due to a maternal 15p;8q insertion. CONCLUSION: This finding of an unbalanced translocation provides further evidence to support previous linkage studies of a potential causative gene on 8q for bipolar disorder.
Aggression↗
The association of different urinary proteins with calcium oxalate hydromorphs. Evidence for non-specific interactions.
It has been proposed that various urinary proteins interact specifically with different calcium oxalate hydromorphs and these interactions have important implications regarding the understanding of the onset and progress of kidney stone disease. Calcium oxalate monohydrate and dihydrate crystals were grown and characterised thoroughly to establish sample purity. These crystals were then incubated in artificial urine samples containing isolated urinary macromolecules. Crystal growth was prevented by saturating the incubation mix with calcium oxalate, and this was confirmed through electron microscopy and calcium measurements of the incubation mix. The surface interactions between the different calcium oxalate hydrates and urinary proteins were investigated by the use of Western blots and immunoassays. The same proteins, notably albumin, Tamm-Horsfall protein, osteopontin and prothrombin fragment 1, associated with both hydrates. There was a trend for more protein to associate with calcium oxalate dihydrate, and greater quantities of different proteins associated with both hydrates when Tamm-Horsfall protein was removed from the incubation mix. There is no evidence from this study to indicate that particular proteins interact with specific calcium oxalate hydrates, which in turn suggests that these protein-mineral interactions are likely to be mediated through non-specific charge interactions.
Adult↗
Imaging for kidney stones.
Imaging investigations play a vital role in the management of patients with kidney stones. The techniques available include plain x-ray of the abdomen, ultrasound scan, intravenous urogram, computed tomography (CT) and magnetic resonance imaging, amongst others. All of these techniques have their own individual roles to play and also have limitations. CT has been establishing itself as the imaging technique of choice and some exciting developments are on the way. However, renal stone disease is a complex condition. Furthermore, there are a variety of surgical techniques used to treat stones. It is therefore important that the strengths and weakness of each of the modalities are clearly understood and the investigations are tailored to address the problem in hand.
Humans↗
A stone farm: development of a method for simultaneous production of multiple calcium oxalate stones in vitro.
We have previously shown how individual calcium oxalate stones of about 1 cm can be grown in vitro. While this proved a design concept, it was severely limited as an experimental tool because of the time required to undertake comparative studies. Here we describe a development of this system in which six parallel pairs of stone generators are supplied with feed solutions generating a medium that is supersaturated with calcium oxalate. Twelve stones were grown simultaneously in aseptically prepared artificial urine over a period of 32 days from 100 mg to about 250 mg. Flow rates, pH and [Ca(2+)] were stable and reproducible over the course of the experiment. Sodium azide (0.02%) was included in the growth medium of six stones and caused a modest decrease in growth rate from 5.5 to 3.4 mg/day. The experimental design is such that this was readily detectable both visually and statistically ( p<0.001). This multiple stone growing system ("a stone farm") shows improved consistency and illustrates the statistical power of the technique. Azide has only a minor effect on the growth kinetics and can be used as an antibacterial agent in studies involving urinary macromolecules. The technique is suitable for practical and meaningful investigation of calcium oxalate stone formation in vitro.
Calcium Oxalate↗
Enlargement of calcium oxalate stones to clinically significant size in an in-vitro stone generator.
OBJECTIVE: To develop and validate an in vitro method suitable for the quantitative investigation of the growth of calcium oxalate stones through to a clinically significant size. MATERIALS AND METHODS: Small fragments of calcium oxalate calculi were suspended in a mixed suspension/mixed product removal crystalliser supplied with artificial urine supersaturated with calcium oxalate. The fragments were weighed at regular intervals until they reached approximately equal 500 mg. The results were plotted as weight against time and fitted to equations corresponding to constant increase in diameter, surface area-controlled and constant-deposition growth patterns. The choice of the most appropriate model was based on the squared regression coefficient (r2). RESULTS: Eight fragments (2-6 mm in diameter) were grown to approximately 10 mm in diameter over periods from 137 to 369 h. Seven of the growth curves were best-fitted (r2 > or = 0.988) by the equation w = kt(3/2) + c, where w is the weight, k is a growth constant, t is the time and c is a constant approximating to the initial weight. This corresponds to a surface area-dependent mechanism. CONCLUSIONS: The growth of these small fragments to a clinically significant size accelerated throughout the experimental period in a way which was consistent with a surface area-dependent mechanism. We have developed a resilient model suitable for studying the kinetics of calcium oxalate stone growth in vitro.
Calcium Oxalate↗
Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.
Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl kinase domain known to form a critical hydrogen bond with the drug. This substitution of threonine with isoleucine was sufficient to confer STI-571 resistance in a reconstitution experiment. In three patients, resistance was associated with progressive BCR-ABL gene amplification. These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance.
Amino Acid Sequence↗
Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans.
Wnt-4, a member of the Wnt family of locally acting secreted growth factors, is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups. Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans. In this article, we show that, in testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry. Furthermore, we elucidate a possible mechanism for human XY sex reversal associated with a 1p31-p35 duplication including WNT-4. Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype. Thus, WNT-4, a novel sex-determining gene, and DAX1 play a concerted role in both the control of female development and the prevention of testes formation. These observations suggest that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway.
Amino Acid Sequence↗
Prenatal diagnosis using interphase fluorescence in situ hybridization (FISH): 2-year multi-center retrospective study and review of the literature.
Since 1993, the position of the American College of Medical Genetics (ACMG) has been that prenatal interphase fluorescence in situ hybridization (FISH) is investigational. In 1997, the FDA cleared the AneuVysion assay (Vysis, Inc.) to enumerate chromosomes 13, 18, 21, X and Y for prenatal diagnosis. Data is presented from the clinical trial that led to regulatory clearance (1379 pregnancies) and from retrospective case review on 5197 new pregnancies. These studies demonstrated an extremely high concordance rate between FISH and standard cytogenetics (99.8%) for specific abnormalities that the AneuVysion assay is designed to detect. In 29 039 informative testing events (6576 new and 22 463 cases in the literature) only one false positive (false positive rate = 0.003%) and seven false negative results (false negative rate = 0.024%) occurred. A historical review of all known accounts of specimens tested is presented (29 039 using AneuVysion and 18 275 specimens tested with other probes). These performance characteristics support a prenatal management strategy that includes utilization of FISH for prenatal testing when a diagnosis of aneuploidy of chromosome 13, 18, 21, X or Y is highly suspected by virtue of maternal age, positive maternal serum biochemical screening or abnormal ultrasound findings.
Chromosome Aberrations↗
Nephrostomy tube or 'JJ' ureteric stent in ureteric obstruction: assessment of patient perspectives using quality-of-life survey and utility analysis.
INTRODUCTION: Upper urinary tract obstruction is often relieved by either a percutaneous nephrostomy tube (PCN) or a ureteric stent. Both can cause considerable morbidity and reduce patient's health-related quality of life (QoL). We have compared the QoL in these 2 groups. PATIENTS AND METHODS: 34 patients (21 stent and 13 PCN) with unilateral ureteric obstruction were prospectively studied. Each patient completed a questionnaire, which included a common single health index (EuroQol EQ-5D) and intervention-specific questions to assess pain, urinary symptoms and day-to-day problems. RESULTS: There were 22 male and 12 female patients [mean age 56+/-9 years (PCN) and 55+/-14 years (stent)]. The mean duration between the intervention and conduct of the survey was 12+/-5 days for PCN and 28+/-14 days for stent. There was no different in the mean EuroQol score (p = 0.199) and analogue score (p = 0.596) indicating no differences in the gross defects in physical and psychosocial function and the utility between the 2 groups. There was a significant difference in the urinary symptoms (p<0.0001) with patients who had a stent experiencing significantly more irritative urinary symptoms. This group also suffered discomfort for a greater duration and in various postures requiring more analgesia (although not significant with Bonferroni correction). Patients with PCN required more help in the daily care of the nephrostomy tube. There was no difference in the incidence of infections and the need for antibiotics. CONCLUSIONS: Patients with 'JJ' stents have significantly more irritative urinary symptoms and a high chance of local discomfort than patients with nephrostomy tubes (PCN). However, based on the EuroQol analysis, there is no significant difference in the gross impact on the health-related QoL or the utility between these groups indicating no patient preference for either modality of treatment.
Adult↗
XXY male mice: an experimental model for Klinefelter syndrome.
Klinefelter syndrome (47,XXY) is the most common sex chromosome aneuploidy in men. Thus, it is important to establish an experimental animal model to explore its underlying molecular mechanisms. Mice with a 41,XXY karyotype were produced by mating wild-type male mice with chimeric female mice carrying male embryonic stem cells. The objectives of the present study were to characterize the testicular phenotype of adult XXY mice and to examine the ontogeny of loss of germ cells in juvenile XXY mice. In the first experiment the testicular phenotypes of four adult XXY mice and four littermate controls (40,XY) were studied. XXY mice were identified by either Southern hybridization or karyotyping and were further confirmed by fluorescence in situ hybridization. The results showed that the testis weights of adult XXY mice (0.02 +/- 0.01 g) were dramatically decreased compared with those of the controls (0.11 +/- 0.01 g). Although no significant differences were apparent in plasma testosterone levels, the mean plasma LH and FSH levels were elevated in adult XXY mice compared with controls. The testicular histology of adult XXY mice showed small seminiferous tubules with varying degrees of intraepithelial vacuolization and a complete absence of germ cells. Hypertrophy and hyperplasia of Leydig cells were observed in the interstitium. Electron microscopic examination showed Sertoli cells containing scanty amounts of cytoplasm and irregular nuclei with prominent nucleoli. The junctional region between Sertoli cells appeared normal. In some tubules, nests of apparently degenerating Sertoli cells were found. In the second experiment the ontogeny of germ cell loss in juvenile XXY mice and their littermate controls was studied. Spermatogonia were found and appeared to be morphologically normal in juvenile XXY mice. Progressive loss of germ cells occurred within 10 days after birth. This resulted in the absence of germ cells in the adult XXY mice. We conclude that a progressive loss of germ cells occurring in early postnatal life results in the complete absence of germ cells in adult XXY mice. The XXY mouse provides an experimental model for its human XXY counterpart, Klinefelter syndrome.
Animals↗
Increase in the incidence of dapsone hypersensitivity syndrome--an appraisal.
There has been an increase in the reports of dapsone hypersensitivity syndrome (DHS) in the past few years, coinciding with the introduction of multidrug therapy (MDT) for leprosy world-wide. The exact cause of this phenomenon is not clear. We report four cases of DHS observed among 252 leprosy patients on MDT and one case of DHS in a patient taking dapsone for nodulocystic acne in the Dermatology Department of the Osmania General Hospital, Hyderabad, India, between June 1997 and January 1999 with few unusual features. In two of these five patients maculopapular rash was severe and progressed to erythroderma. Introduction of MDT in 1982 has not only decreased the prevalence of leprosy but also brought about a positive change in the attitude of people which increased the voluntary reporting of leprosy patients. This, coupled with improvements in organization of leprosy control and awareness among medical personnel of DHS, are probably the most important reasons for the increased reporting of DHS in recent years.
Adolescent↗
A practical large-scale synthesis of 17alpha-acetoxy-11beta-(4-N, N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914).
A new practical synthesis of 17alpha-acetoxy-11beta-(4-N, N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914) is described. The synthesis gives easily isolable solids at all steps and is amenable to large-scale process.
Chromatography, Thin Layer↗
Early observations of the effect of extracorporeal shockwave lithotripsy on blood pressure: a prospective randomized control clinical trial.
OBJECTIVE: To determine, in a randomized controlled clinical trial, the effect of extracorporeal shock wave lithotripsy (ESWL) on blood pressure. PATIENTS AND METHODS: The trial included 228 patients with small (< 15 mm) asymptomatic calyceal stones who were randomised to undergo ESWL (113 patients) or to an untreated (observed) control group (115 patients). Blood pressure was recorded at randomization using a standardized protocol. Patients undergoing ESWL received a mean (SD) of 5281 (3462) shocks over a mean of 1.75 sessions on one of two lithotripters. Patients were then followed annually, assessing blood pressure and changes in medication. Data were analysed on an intention-to-treat basis. RESULTS: At randomization, 43% of patients in the control group and 53% in the ESWL group were hypertensive. Of the 228 randomized, 200 patients completed at least one annual follow-up, of whom 192 (93 in the control and 99 in the ESWL group) had their blood pressure recorded. The mean follow-up was 2.2 years; 35 (37%) patients in the control and 46 (46%) in the ESWL group were hypertensive (P = 0.19). Seven (7%) patients in the control group and 11 (11%) in the ESWL group were newly diagnosed to be hypertensive (P = 0.35). CONCLUSIONS: In this randomized controlled clinical trial there was no evidence that ESWL causes changes in blood pressure.
Aged↗
Calcium oxalate crystallization kinetics studied by oxalate-induced turbidity in fresh human urine and artificial urine.
We have studied the kinetics of oxalate-induced turbidity in fresh human urine and artificial urine. Assays are performed in 96-well plates, which allows many oxalate concentrations to be studied, repeatedly, in a short time. The metastable limit is defined in terms of the lowest oxalate concentration that gives a rate of change of attenuance significantly greater than the control. Interpretation of rates above this limit is based on ln/ln plots of initial rates against added oxalate concentration. This approach has a good theoretical basis, is well supported by our results and gives a turbidity rate index that is related to the product of the growth rate constant and a factor relating to the number and characteristics of the heteronuclei responsible for initiation of crystallization. This interpretation is posited upon the assumptions that second-order crystallization kinetics occur in unseeded urine when supersaturation exceeds the metastable limit and that aggregation during the initial phase of crystallization does not significantly contribute to changes in turbidity. Metastable limits of urine from healthy volunteers corresponded to a calcium oxalate supersaturation ratio of approx. 10. The turbidity rate index was higher in human urine than in artificial urine. The metastable limit, based on either oxalate concentration or supersaturation, for induction of calcium oxalate crystallization in normal human urine is higher than is likely to be found in normal subjects in vivo. The shape of the relationship between the metastable limit (based on oxalate concentration) and calcium concentration emphasizes the benefit of achieving a low urine calcium concentration. Comparison of the turbidity rate indices for human and artificial urine suggests that the role of nucleation promoters is more dominant than that of growth inhibitors.
Calcium↗
Detection of abnormal pretransplant clones in progenitor cells of patients who developed myelodysplasia after autologous transplantation.
Secondary myelodysplastic syndromes (MDS) have been reported after autologous transplantation. It is not known whether the MDS results from the pretransplant conventional-dose chemotherapy or from the high-dose chemotherapy (HDC) used for the transplant procedure. We performed a multicenter, retrospective analysis of morphologically normal pretransplant marrow or stem cell specimens from 12 patients who subsequently developed myelodysplasia after HDC. To determine if the abnormal clone was present before HDC, we used fluorescence in situ hybridization (FISH) to detect the cytogenetic markers observed at the onset of posttransplant MDS. Cryopreserved, pretransplant bone marrow, peripheral blood stem cell specimens, obtained at the time of harvest, or archival smears were used. Standard cytogenetic analysis had been performed pretransplant in four patients, showing a normal karyotype. In 9 of 12 cases, the same cytogenetic abnormality observed at the time of MDS diagnosis was detected by FISH in the pre-HDC specimens. Our findings support the hypothesis that, in many cases of posttransplant MDS, the stem cell damage results from prior conventional-dose chemotherapy and may be unrelated to HDC or the transplantation process itself.
Adult↗
Calcium oxalate crystallization kinetics at different concentrations of human and artificial urine, with a constant calcium to oxalate ratio.
The effect of in vitro dilution of artificial urine or human urine on the crystallization of calcium oxalate was examined in a mixed suspension, mixed product removal crystallization system. Direct growth inhibition by components of artificial urine was not significant and supersaturation was the dominant factor in determining crystal nucleation and growth rates. Dilution of human urine caused a decrease in crystal growth rate that was independent of the input calcium and oxalate concentrations, suggesting that dilution of growth inhibitors could be physiologically more important than any reduction in supersaturation. This loss of growth inhibition was counteracted by a reduction in nucleation promotion, with the net effect that the mass of crystals declined. Correlation of crystallization measurements with urinary concentration (osmotic pressure) confirmed these observations, with a negative relationship for growth rate and a positive relationship for nucleation rate and suspension density. Increasing the concentration of urine shifts the crystallization balance from low nucleation/high growth to high nucleation/low growth. Calcium oxalate crystalluria in healthy urine is therefore less likely at early stages of urine development in the nephron and the likelihood can be further reduced by increased fluid output. Our results suggest that lowering the heterogeneous nucleation activity by dilution is more than sufficient to override the loss of growth inhibition.
Calcium↗