Is percutaneous nephrolithotomy safe in chronic kidney disease patients!!!

Introduction: Management of renal calculus in a patient of chronic kidney disease (CKD) is always challenging. Treatment options include extracorporeal shock wave lithotripsy, retrograde intrarenal surgery, and percutaneous nephrolithotomy (PCNL). With PCNL being gold standard for renal calculus ≥1.5 cm in normal kidneys, we aimed to analyze the safety and efficacy of PCNL in CKD patients with calculus ≥1.5 cm. Materials and Methods: Sixty patients of CKD with renal calculus were included in the study: Group A with glomerular filtration rate (GFR) ≤30 ml/min/m2 and Group B with GFR >30 <60 ml/min/m2. The estimated GFR (eGFR) pre-PCNL, peak eGFR on follow-up, and eGFR at last follow-up, stone free rates, and complications were recorded. The CKD stage before and after PCNL were also compared at the last follow-up. Results: The mean age of patients was 52 years. A mean of 1.14sittings per renal unit was required for PCNL. Complete clearance was 94% after all auxiliary procedures. The mean prePCNL eGFR was 26.5 ± 4.01 and 43.6 ± 9l. 14 ml/min/1.73 m2 in Groups A and B, respectively. The mean post-PCNL eGFR was 32 ± 9.94 and 51 ± 8.85 ml/minute/1.73 m2, respectively, in Groups A and B. At a mean follow-up of 180 days, deterioration with the migration of CKD stage was seen in 13 patients (21.6%) out of which 10 patients were of Groups A and 3 in Group B. Six patients (10%) required maintenance hemodialysis. Postoperative bleeding complication requiring blood transfusions was seen in 12 (20%) and 3 (5%) required intensive care unit care postoperatively. No mortality was observed in our study. Conclusion: PCNL is an effective management strategy for renal calculus in patients with CKD with an acceptable stone clearance rates and manageable complications. Peak eGFR <30 ml/min/m2 and postprocedure complications predict deterioration and need for RRT.

A comparative study of minimally invasive percutaneous nephrolithotomy and retrograde intrarenal surgery for solitary renal stone of 1-2 cm.

BACKGROUND: PCNL is the treatment of choice for renal stones. But wide array of complications due to larger tract size(>20 Fr) has lead to development of improved techniques like miniPCNL(<20 Fr) and RIRS(Retrograde intrarenal surgery). AIM AND OBJECTIVE: To perform a study comparing miniPCNL with RIRS for renal stones 1-2 cm with respect to stone free rate , complications and quality of life. MATERIALS AND METHODS: A prospective, randomised study was carried out our tertiary care centre, recruiting 40 patients in each group from Dec 2016 to Oct 2018. Patients demographic characteristics, operative findings, surgical outcomes and quality of life( SF-36 questionnaire) were recorded with 3 months of follow-up. RESULTS: RIRS has longer operative time (69.75 min > 51.58 min; p=0.003), lesser radiation exposure (p=0.012), shorter hospital stay (p =0.15), lesser blood loss and lesser post operative pain on POD1 and POD2 (p =0.005, p=0.001 respectively). RIRS group patients sufferred more post op complications (p=0.03 )of which urosepsis was most common. Stone free rate is significantly better(p =0.003) in miniPCNL group on POD1 , while SFR's at 1 month (miniPCNL-90% and RIRS -85%) and 3 month (miniPCNL- 92.5% and RIRS -87.5%) was better in miniPCNL group, but statistically insignificant.On subgroup analysis SFR in lower pole calculus was better in miniPCNL group at 1month and 3 month (p=0.008). Second intervention for stone clearance was required in 3 patients of miniPCNL and 5 patients of RIRS, out of which 4 had lower pole stone.No significant differnce was found in quality of life in both groups at 1 month. CONCLUSION: MiniPCNL is a better treatment modality for higher single step stone free rate, shorter operative time and fewer postop complication. RIRS has SFR slightly less than miniPCNL but has less radiation exposure and much less post operative pain. There is no significant difference in quality of life in both groups.

An Enhanced Symptom Clustering with Profile Based Prescription Suggestion in Biomedical application.

The application of data mining has been increasing day to day whereas the data base is also enhancing simultaneously. Hence retrieving required content from a huge data base is a critical task. This paper focus on biomedical engineering field, it concentrates on initial stage of database such as data preprocessing and cleansing to deal with noise and missing data in large biomedical data sets. The database of biomedical is huge and enhancing nature retrieving of specific content will be a critical task. Suggesting prescription with respect to identified disease based on profile analysis of specific patient is not available in current system. This paper proposes a recommendation system of prescription based on disease identification is done by combining user and professional suggestion with profile based analysis. Hence this focuses on profile based suggestions and report will be generated. The retrieving of specific suggestion from a huge database is done by hybrid feature selection algorithm. This approach focuses on enabling recommendation based on user profile and implementing Hybrid feature selection algorithm to retrieve specific content from a huge database. Hence it attains better retrieval of required content from a huge database compared to other existing approaches and suggests better recommendation with respect to user profile.

Aberrant nuclear expression of AP-1 and NFkappaB in lymphocytes of women stressed by the experience of breast biopsy.

We have investigated the expression of AP-1 and NFkappaB in peripheral blood lymphocytes of women scheduled for breast biopsy. Samples were collected when women were informed of the need for biopsy (prebiopsy, T1, 5-7 days prior to the actual biopsy) and 7-10 days after they learned the result of their biopsy (postbiopsy, T2). At the time of blood collection, psychological stress was evaluated using Speilberger's State Trait Anxiety Inventory (STAI) and the Profile of Mood States (POMS). Women scheduled to undergo breast biopsy reported significant increases in anxiety (STAI) and mood disturbance (POMS). Gel shift mobility assays showed that mitogen stimulated peripheral blood lymphocytes of these women were less capable of the nuclear expression of AP-1 or NFkappaB at T1. Similar assessments, 7-10 days after the women learned of the results of their breast biopsy, showed these same women to have a marked reduction in anxiety and mood disturbance and an increased nuclear translocation of AP-1 and NFkappaB. These results show a significant decrease in nuclear AP-1 and NFkappaB expression during the period of emotional distress prior to biopsy with a return of nuclear transcription activity to normal levels when distress was relieved. Several studies have correlated increased psychological stress with decreased immune function. The results of this study suggest that psychological stress may mediate immunosuppression by altering the expression of the transcription factors, AP-1 and NFkappaB.

Curcumin blocks cyclosporine A-resistant CD28 costimulatory pathway of human T-cell proliferation.

INTRODUCTION: Curcumin (Cur) is a phenolic component of common spice, turmeric. We have reported earlier that it possesses antineoplastic and immunosuppressive properties in vitro. It has been reported that cyclosporine A (CyA), a commonly used immunosuppressant does not inhibit CD28 costimulatory pathway of T-cell activation. We hypothesized that Cur, a tyrosine kinase inhibitor, would block CyA-resistant CD28 costimulatory pathway of human T cell proliferation. MATERIALS AND METHODS: Human T-lymphocytes were isolated from healthy donors using gradient centrifugation and rosetting techniques. In four separate experiments T-cells were plated in triplicate in 96-well plates at a density of 2X105 cells/well. These cells were stimulated with 0.5 ng/ml phorbol myristate acetate (PMA) + 0.5 (g/ml anti-CD28 antibody (PMA-CD28 group) or 2.5 microgram/ml PHA (PHA group). Cur or CyA at varying concentrations (0.31, 0.625, 1.25, 2.5, 5, or 10 microgram/ml and 1.25, 2.5, 5, 10, 20, or 250 ng/ml, respectively) was added and cellular proliferation was measured by the uptake of [3H]thymidine and is reported (mean cpm/well(SD). Cells from the PMA-CD28 group that were treated with either curcumin or 0.4% DMSO (vehicle control for curcumin) were studied for evidence of apoptosis by staining with viable dyes MC540 and Hoechst 33342 and subsequently analyzed in the cell sorter. RESULTS: Cur caused a concentration-dependent inhibition of T-cell proliferation in the PMA-CD28 group (from 32775 +/- 3084 to 66 +/- 42 at 5.0 microgram/ml of cur) and PHA group (from 50956 +/- 5747 to 24 +/- 12 at 5.0 microgram/ml) with a calculated ED50 of 3.5 and 7.7, microM respectively. CyA inhibited T-cell proliferation in the PHA group with a calculated ED50 of 2.7 ng/ml but failed to block PMA + anti-CD28-stimulated T-cell proliferation even at 250 ng/ml. PMA-CD28 group cells treated with 10 microgram/ml curcumin showed a significantly increased apoptosis as compared to control (0.4% DMSO). CONCLUSION: Since Cur blocks the CyA-resistant PMA + anti-CD28 pathway of T-cell proliferation, it may have novel adjuvant immunosuppressive properties.

Altered expression of CD44 in human prostate cancer during progression.

There is a great need for markers that distinguish slowly progressive from rapidly progressive prostate cancers in paraffin-embedded tissues. CD44, an adhesion molecule that has been useful for the prediction of prognosis in some other cancers, has not been described in prostate cancer. The expression of CD44 was investigated with the monoclonal antibody GKW.A3 in prostate cancer in formalin-fixed, paraffin-embedded tissue sections of (1) whole prostates from 50 patients with 74 prostate cancers; and (2) lymph node metastases from 14 patients. Sixty percent of primary prostate cancers expressed CD44 moderately to strongly. No metastases expressed CD44 moderately to strongly; only 14% of metastases expressed even low levels of immunohistochemically detectable CD44. There is a difference between primary and metastatic prostate cancer (P <.0006) in the expression of CD44 and an inverse correlation (P <.05) between histological differentiation (Gleason grade) and the expression of CD44. The magnitude of the differential expression of CD44 in primary and metastatic prostate cancers suggests it should be investigated as an indicator of prognosis in a large prospective study.

CWR22: the first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivo and in soft agar.

Most patients' prostate cancers respond to androgen deprivation but relapse after periods of several months to years. Only two prostate cancer xenografts, LNCaP and PC-346, have been reported to be responsive to androgen deprivation and to relapse subsequently. Both of these tumors shrink slightly, if at all, and relapse less than 5 weeks after androgen withdrawal. After androgen withdrawal, the human primary prostate cancer xenograft CWR22 regresses markedly, and prostate-specific antigen (PSA) falls up to 3000-fold in the blood of mice. PSA usually returns to normal. In some animals, the tumor relapses and is then designated CWR22R. In these animals, PSA starts to rise approximately 2-7 months, and tumor begins to grow 3-10 months after castration. Animals with CWR22 need to be euthanized because of large tumors 6-12 weeks after the transplantation of CWR22. Androgen withdrawal prolongs life approximately 3-4-fold.

Expression of E-cadherin in primary and metastatic prostate cancer.

Immunohistochemical studies have suggested that E-cadherin may be a useful prognostic marker in prostate cancer. Previous studies have depended on cryostat sections of tissues selected grossly. Many prostate cancers, even when extensive, are not visible grossly; many others cannot be demarcated sharply grossly. The wide applicability of prognostic markers after total prostatectomy will depend upon methods that can be applied to tissue selected based upon the histopathological examination of the entire prostate. Our purpose was to investigate the possibility that E-cadherin could be demonstrated in paraffin-embedded whole prostates and metastatic prostate cancer. Microwaving in citrate buffer was the best of five methods tested for the demonstration of E-cadherin in paraffin-embedded prostate and was used to investigate 53 primary prostate cancers from 44 patients and lymph node metastases from 14 patients. Metastases of prostate cancer to lymph nodes expressed less (P = 0.008) E-cadherin than primary prostate cancers. The expression of E-cadherin correlated with the histopathological differentiation (Gleason grade) of primary prostate cancers (P = 0.03, Ptrend = 0.003). The use of monoclonal anti-human E-cadherin (HECD-1) with microwaving in citrate buffer followed by immunoperoxidase staining with heavy metal enhancement for the demonstration of E-cadherin in paraffin-embedded tissue will, for the first time, allow the use of archival tissue for prognostic studies of E-cadherin in prostate cancer and other tissue. Our results are consistent with the hypothesis that aggressive prostate cancers exhibit decreased expression of E-cadherin and demonstrate the feasibility of long-term prognostic studies of this molecule in the usually multiple prostate cancers found in whole, formalin-fixed, paraffin-embedded resected prostates.

Prostatic intraepithelial neoplasia and other changes during promotion and progression.

Preneoplastic lesions, early neoplastic lesions and carcinomas in situ have been demonstrated to be of great value for many purposes in many organ systems. Their recognition can be useful in epidemiological studies and can facilitate the selection of patients for therapeutic interventions. They can be used as "surrogate endpoint biomarkers" in studies aimed at the chemoprevention of cancers. In the lung, colon and various other organs, such markers are well recognized to be associated with the development of cancer in man. In the livers and colons of experimental animals, there has been detailed characterization of "enzyme-altered foci" (EAF) as "putative preneoplastic markers." The words "surrogate" and "putative" are important; the biological potential of these lesions needs to be elucidated in much greater detail. The quantification of early lesions that are associated with and sometimes precursors of neoplasia is of particular value because they are much more numerous, in most organ systems, than the carcinomas that develop in the same organs. The most abundant of these lesions show minimal or no morphological alterations. For example, EAF and aberrant crypts are more numerous than polyps in the colons of patients and experimental animals with cancer or precancerous conditions that affect the colon. Currently, there are few well documented putative or surrogate markers that are highly associated with the development of prostatic carcinoma in man. The best documented among these is prostatic intraepithelial neoplasia. We have recently reported the identification of EAF in the human prostate. While they share many phenotypic alterations with prostatic intraepithelial neoplasia, much remains to be accomplished if their biological fate is to be understood.

Detection of alpha-thalassemias by multiplex polymerase chain reaction.

Although alpha-thalassemia is the most common genetic abnormality in the world, there is currently no routine laboratory method to definitively identify individuals who are affected. We describe a rapid and simple method that utilizes deletion-sensitive primers to amplify normal DNA sequences. Deletions involving the regions responsible for most of the alpha-thalassemia cases in the US prevent amplification with these primers. In tests with DNA isolated from small amounts (10 microL) of whole blood, the deletion-sensitive primers gave rise to the expected 248- and 375-bp (base pair) amplification products in normal individuals. These primers, along with primers designed to bind to a nonaffected control sequence from the hemoglobin beta chain, could be amplified simultaneously (multiplex polymerase chain reaction). This made it possible to detect heterozygotes for alpha-thalassemia-2 (one alpha locus deleted) by determining the ratios of the 248- and 375-bp amplification products to the product of the control sequence (268 bp). The method is rapid and simple and can be performed in a routine clinical laboratory.

A novel approach to the characterization of whole prostate pathology in glycol methacrylate.

The controversial and subjective nature of the classification of many prostatic lesions and the increasing recognition that lesions that occur in different topographical regions or zones of the prostate may differ in their biological behavior suggest that new approaches are needed to increase our understanding of the biology of prostatic diseases. The precise recognition and identification of prostatic lesions are prerequisites for studies of their biological behavior. We have developed a novel method for the embedding of whole prostates in glycol methacrylate at low temperatures. Enzyme histochemical procedures that can be conducted with this approach have revealed previously unrecognized features of prostatic intraepithelial neoplasia and have demonstrated the presence of prostatic lesions that resemble enzyme-altered foci that have been reported and characterized extensively in other organ systems.

Putative preneoplastic foci in the human prostate.

Our knowledge of prostate cancer is less well-defined than our knowledge of cancers of other organs. In the colon, for example, morphological criteria to identify carcinomas in situ and some putative preneoplastic lesions are clear; phenotypic differences in the expression of enzymes and antigens are documented in experimental models and are starting to be defined in humans. Experimental models of cancer of the liver and colon show evidence that "enzyme-altered foci" are preneoplastic. In these organs, the "normal" context is much clearer than in the prostate. In contrast, in the prostates of men in the same age range as those who develop prostate cancer, morphological aberrations are almost always present, diverse, and poorly understood. Murphy and Gaeta said that, "in the study of prostatic disease..., almost every aspect remains controversial...[and].... many of the 'known facts' concerning prostatic disease are poorly documented..." While being aware that the definitions of all benign and malignant lesions of the prostate are based on complex morphological criteria which must form the contemporary context for comparisons, our laboratory is searching for markers that will permit the identification of putative preneoplastic lesions in the prostate. In our opinion, these changes will not be found most efficiently, if they are present at all, in long established cell lines, advanced carcinomas, or serially transplantable xenografts of primary prostatic carcinomas. Our preliminary data suggest that several enzyme histochemical and immunohistochemical approaches are worthy of study. Markers that show promise include acid phosphatase, 5'-nucleotidase, leucine aminopeptidase, and CD44.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticarcinogenic action of diallyl sulfide in hamster buccal pouch and forestomach.

The anticarcinogenic action of the garlic constituent diallyl sulfide (DAS), was examined in the hamster buccal pouch and forestomach. Groups of hamsters were topically treated, for up to 14 weeks, with a 0.5% solution of the buccal pouch and forestomach carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Prior to, during and after DMBA treatment, groups of hamsters were also treated, on alternate days, with a 1% solution of DAS. In addition to tumor formation, the induction of gamma-glutamyl transpeptidase (gamma GT) buccal pouch epithelial lesions served as an additional presumptive index of in vivo carcinogenesis/anticarcinogenesis. DAS resulted in a significant reduction in buccal pouch tumor frequency, buccal pouch tumor burden, buccal pouch gamma GT lesion frequency and forestomach tumor frequency. In a separate experiment, DAS also reduced the level of autoradiographically quantified unscheduled DNA repair synthesis (UDS) in pieces of hamster buccal pouch concurrently exposed in vitro to the potent buccal pouch carcinogen N-methyl-N-benzylnitrosamine (MBN). This study demonstrates that DAS is an effective anticarcinogenic agent in squamous mucosa of the hamster and suggests novel cost-effective strategies for the rapid identification of tissue-specific anticarcinogens and a quantitative assessment of their efficacy.

Curcumin as an inhibitor of cancer.

Curcumin I (Cur I) and curcumin III (Cur III) are the yellow coloring phenolic compounds isolated from the spice turmeric. The effect of curcumins on different stages of development of cancer was studied. Cur I inhibited benzopyrene- (BP) induced forestomach tumors in female Swiss mice, and Cur III inhibited dimethylbenzanthracene- (DMBA) induced skin tumors in Swiss bald mice. Cur I also inhibited DMBA-initiated, tetradeconyl phorbol acetate-promoted skin tumors in female Swiss mice. In vitro 3H-BP-DNA interaction studies, and in vivo carcinogen metabolizing enzyme studies revealed that curcumins exert anticarcinogenic activity by altering the activation and/or detoxification process of carcinogen metabolism. Cur I and Cur III also exhibit in vitro cytotoxicity against human chronic myeloid leukemia, which is dose dependent. This study shows that curcumins inhibit cancer at initiation, promotion and progression stages of development.

Mutagenicity and carcinogenicity of tea, Camellia sinensis.

Aqueous, caffeine free and tannin fractions of commercial tea and tannic acid were tested for mutagenicity in Ames test. Tea fractions of tannic acid were non mutagenic in strains TA 100, TA 98, TA 1535 and TA 1538 of Salmonella typhimurium with or without metabolic activation (rat-S9 mix) at different doses tested. In strain TA 98 the above tea fractions and tannic acid inhibited the S9 mix mediated mutagenicity of tobacco in a dose dependent manner. The different tea fractions at 60 degrees C, did not increase the tumor incidence in Swiss mice by gavage feeding. They also failed to produce tumors when injected subcutaneously. Caffeine free tea extract decreased the tobacco induced liver tumors but had no effect on lung tumors. The same fraction was ineffective in hexachlorocyclohexane induced liver tumors in Swiss mice.

Effect of vitamin A status of rats on metabolizing enzymes after exposure to tobacco extract or N'-nitrosonornicotine.

The effects of N'-nitrosonornicotine (NNN) and tobacco extract on hepatic and pulmonary biotransformation enzymes were studied in rats fed vitamin A-sufficient or -deficient for semisynthetic diets. Basal levels of cytochrome P450, benzo[a]pyrene hydroxylase, benzphetamine demethylase, glutathione S-transferase and glutathione were lower in the group on the deficient diet. Treatment with tobacco extract or NNN significantly increased the levels of these enzymes in the sufficient diet group. However, in the deficient group, phase I enzymes were significantly increased, but glutathione and glutathione S-transferase levels were drastically reduced. Urine from animals on the deficient diet and treated with tobacco extract or NNN were mutagenic in the Ames Salmonella/microsome test. The results suggest that altered metabolism resulting from a vitamin A-deficient diet may be an important factor in susceptibility to carcinogens.

Acute inhibition of DNA synthesis in hamster buccal pouch epithelium exposed to indirect acting carcinogens.

Inhibition of DNA synthesis was observed and quantitated in hamster buccal pouch epithelium exposed in vivo and in vitro to indirect acting carcinogens. Topical application of a 0.5% solution of the potent hamster buccal pouch carcinogen 7,12-dimethylbenz[a]-anthracene (DMBA) acutely inhibited epithelial DNA synthesis by 40-65%, as indicated by a decrease in [3H]thymidine incorporation over a period of 24 h. When applied twice at a concentration of 2%, N-methyl-N-benzylnitrosamine (MBN), another potent buccal pouch carcinogen, inhibited epithelial DNA synthesis by 76% within a period of 4 h. A similar acute inhibitory effect on DNA synthesis was observed when explants of buccal pouch mucosa, exhibiting continuous cell replication, were exposed in vitro in the presence of MBN or DMBA for periods up to 12 and 24 h, respectively. The inhibitory effect of DMBA was greater than that of other polycyclic aromatic hydrocarbons of lesser carcinogenic potency in this tissue. This study demonstrates that the metabolic activation of indirect acting carcinogens leading to acute cytotoxicity and inhibition of DNA synthesis occurs rapidly in hamster buccal pouch mucosa exposed to these agents in vitro as well as in vivo. The experimental imposition of an acute inhibitory pressure, applied as demonstrated in this report, may enable the detection of precancerous cells which have acquired the property of resistance to this cytotoxic effect in the course of carcinogenesis. In principle, the in vitro approach, coupled with autoradiography, may be useful in identifying microscopic foci of resistant preneoplastic cells in samples of human oral mucosa. 24R01 34160

Effect of nutritional status on mutagenicity of urine excreted by rats treated with standard/experimental carcinogens.

Urine samples, collected from Sprague Dawley rats treated with extracts of tobacco/masheri, benzo (a) pyrene, N'-nitrosonornicotine, N'-nitrosodiethylamine and maintained on semi-synthetic diets sufficient or deficient in Vitamin A, B and protein were tested for mutagenicity using Salmonella/microsome assay. The mutagenic activity of urine or various treated groups was in the order deficient diet greater than standard laboratory diet greater than nutritionally sufficient diet. Present results confirmed the earlier observations that nutritionally deficient animals are likely to have more exposure to mutagenic metabolites that are generated by increased phase I enzymes and decreased detoxification system.

Hydroxychavicol: a new anti-nitrosating phenolic compound from betel leaf.

Hydroxychavicol and eugenol are the phenolic compounds isolated from betel leaf (piper betel). The modulation of nitrosation of methylurea by sodium nitrite at pH 3.6 and 30 degrees C was studied. The formation of mutagenic N-nitrosomethylurea was monitored by checking the mutagenicity of reaction mixture in Salmonella typhimurium strain TA100 and TA1535 without S9 mix. Hydroxychavicol and eugenol exhibit dose-dependent suppression of nitrosation in vitro without affecting the survival of the bacteria. Pre- or post-treatment of bacterial cells from S. typhimurium strains TA100 and TA1535 with phenolics did not modify the mutagenicity of nitrosomethylurea. The blocking of hydroxy group(s) in the benzene ring by acetylation abolishes the anti-nitrosating activity of the molecule(s). The nitrosation inhibition by hydroxychavicol is through scavenging of nitrite ions in the media, thus making them non-available for the nitrosation of methylurea.