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Rajeev Kumar

Publications and source records attributed to Rajeev Kumar.

At least 19 recordsLinked to original sources
PubMed2025

Moss BRCA2 lacking the canonical DNA-binding domain promotes homologous recombination and binds to DNA.

BRCA2 is crucial for mediating homology-directed DNA repair (HDR) through its binding to single-stranded DNA (ssDNA) and the recombinases RAD51 and DMC1. Most BRCA2 orthologs have a canonical DNA-binding domain (DBD) with the exception of Drosophila melanogaster. It remains unclear whether such a noncanonical BRCA2 variant without DBD possesses a DNA-binding activity. Here, we identify a new noncanonical BRCA2 in the model plant Physcomitrium patens (PpBRCA2). We establish that PpBRCA2 is essential for genome integrity maintenance, somatic DNA double-strand break (DSB) repair, HDR-mediated gene targeting, and RAD51 foci recruitment at DNA break sites. PpBRCA2 is also critical for DSB repair during meiosis. Interestingly, PpBRCA2 interacts strongly with RAD51 but weakly with DMC1, suggesting a distinct meiotic function compared to other BRCA2 homologs. Despite lacking the canonical DBD, PpBRCA2 binds ssDNA through its disordered N-terminal region and efficiently promotes HDR. Our work highlights that the ssDNA binding capacity of BRCA2 homologs is conserved regardless of the presence of a canonical DBD and provides a deeper understanding of BRCA2's functional diversity across species.

BRCA2 Protein↗
PubMed2007

Multimicronutrient supplementation for undernourished pregnant women and the birth size of their offspring: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the effect of multimicronutrient supplementation for undernourished pregnant women on the birth size of their offspring, incidence of low-birth-weight infants (<2500 g), and early neonatal morbidity. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Tertiary care hospital. PARTICIPANTS: Two hundred pregnant women (of 13 465 approached) with a body mass index (calculated as weight in kilograms divided by the square of height in meters) of less than 18.5 and/or a hemoglobin level of 7 to 9 g/dL were enrolled at 24 to 32 weeks of gestation. One hundred forty-six neonates (73.0%) were available for analysis of birth size and 170 (85.0%) for analysis of morbidity in the 7 days after delivery. Intervention The micronutrient supplementation group (n = 99) received a multimicronutrient supplement containing 29 vitamins and minerals once a day, from enrollment until delivery (median duration, 58 days; interquartile range, 37-77 days; compliance, 87%). The comparison group (n = 101) received placebo for 52 (15-66) days, with 85% compliance. All subjects also received supplements of iron (given in the form of ferrous sulfate, containing 60 mg of elemental iron), 60 mg/d, and folic acid, 500 mug/d. MAIN OUTCOME MEASURES: Birth weight, length, midarm circumference, incidence of low birth weight, and early neonatal morbidity. RESULTS: Infants in the micronutrient group were heavier by 98 g (95% confidence interval [CI], -16 to 213 g) and measured 0.80 cm (95% CI, 0.03-1.57 cm) longer and 0.20 cm (95% CI, 0.04-0.36 cm) larger in midarm circumference compared with the placebo group. Incidence of low birth weight declined from 43.1% to 16.2% with multimicronutrient supplementation a (a 70% decrease; relative risk, 0.30; 95% CI, 0.13-0.71; P=.006), and that of early neonatal morbidity declined from 28.0% to 14.8% (a 58% decrease; relative risk, 0.42; 95% CI, 0.19-0.94; P=.04). CONCLUSION: Compared with iron and folic acid supplementation, the administration of multimicronutrients to undernourished pregnant women may reduce the incidence of low birth weight and early neonatal morbidity.

Adult↗
PubMed2007

Transrectal ultrasound-guided biopsy of prostate voxels identified as suspicious of malignancy on three-dimensional (1)H MR spectroscopic imaging in patients with abnormal digital rectal examination or raised prostate specific antigen level of 4-10 ng/ml.

Results of the evaluation of transrectal ultrasound (TRUS) guided needle biopsy of voxels identified as suspicious of malignancy on magnetic resonance spectroscopic imaging (MRSI) in a large cohort of men (n = 83) with abnormal digital rectal examination (DRE) [prostate specific antigen (PSA) 0-4 ng/ml] or PSA less than 10 ng/ml, are reported. Three-dimensional (1)H MRSI was carried out at 1.5 T using a pelvic-phased array coil in combination with an endorectal surface coil. Voxels were classified as suspicious of malignancy based on Cit/(Cho + Cr) metabolite ratio. TRUS-guided biopsy of suspicious voxels was performed using the z- and x-coordinates obtained from MR images and two to three cores were taken from the suspected site. A systematic sextant biopsy was also carried out. MRSI showed voxels suspicious of malignancy in 44 patients while biopsy revealed cancer in 11 patients (25%). Patients who were negative for malignancy on MRSI were also negative on biopsy. An overall sensitivity of 100%, specificity of 54%, negative predictive value of 100% and accuracy of 60% were obtained. The site of biopsy was confirmed (n = 20) as a hypo-intense area on repeat MRI while repeat MRSI revealed high choline and low citrate. The overall success rate of MRI-directed TRUS-guided biopsy of 25% was higher compared with a 9% success rate achieved without MR guidance in another group of 120 patients. Our results indicate that TRUS-guided biopsy of suspicious area identified as malignant from MRSI can be performed using the coordinates of the voxel derived from MR images. This increases the detection rate of prostate cancer in men with PSA level <10 ng/ml or abnormal DRE and also demonstrates the potential of MR in routine clinical practice.

Adenocarcinoma↗
PubMed2007

Apparent diffusion coefficient of the prostate in men prior to biopsy: determination of a cut-off value to predict malignancy of the peripheral zone.

Determination of the apparent diffusion coefficient (ADC) of the prostate in men (n = 60) with raised prostate-specific antigen (PSA) or an abnormal digital rectal examination (DRE) prior to transrectal ultrasound (TRUS) guided biopsy using endorectal DWI is reported. Patients were categorized into different groups based on their PSA levels. The mean ADC was calculated from a number of regions of interest (ROIs) for the whole of the peripheral zone (PZ) and the central gland (CG). A total of 1108 ROIs were analyzed from 60 patients. The mean ADC value of the PZ was higher than that of the CG in controls. A total of 23 out of 60 patients were positive for malignancy on biopsy, and the mean ADC of the PZ was lower in these patients compared with those who were negative. Moreover, the mean ADC obtained for the whole of the PZ of the prostate in different groups of patients and controls showed a decreasing trend. A plot between PSA and mean ADC for the PZ showed non-linear association with logarithmic decrease in ADC. The mean ADC of the CG was not significantly different in patients who were positive or negative for malignancy in biopsy. In addition, a cut-off value of 1.17 x 10(-3) mm2/s (sensitivity = 73% and specificity = 74%, area under the curve = 0.83) for the mean ADC for the whole of the PZ of patients was determined by using the receiver operating characteristic curve (ROC) to predict malignancy of the PZ.

Adult↗
PubMed2007

Malignant non-functional paraganglioma of the bladder presenting with azotemia.

Paragangliomas of the urinary bladder are rare tumors representing less than 1% of bladder tumors and are usually benign. Malignant paragangliomas are uncommon and are defined by their clinical behavior rather than the histologic features. We describe a patient with recurrent nonfunctioning paraganglioma of bladder presenting with hematuria and obstructive uropathy due to involvement of ureteroileal anastomoses. Treatment consisted of excision of recurrent lesion involving both lower ureters with the revision of ureteroileal anastomoses. Histology confirmed the presence of nests of tumor cells with abundant eosinophilic cytoplasm. Immunohistochemically the tumor cells were strongly positive for chromogranin A.

Adult↗
PubMed2006

22pi smaragdyrin molecular conjugates with aromatic phenylacetylenes and ferrocenes: Syntheses, electrochemical, and photonic properties.

Syntheses, spectroscopic, electrochemical, and third-order nonlinear optical susceptibilities of a series of 22pi smaragdyrins and their corresponding Rh(I) derivatives bearing phenylacetylene substituents and ferrocene-containing substituents are reported. The synthetic strategy involved a [3 + 2] acid-catalyzed oxidative coupling reaction of the appropriate dipyrromethane and oxatripyrrane. The desired meso substituents, such as phenylacetylenylphenyl and the ferrocenes, were incorporated to the dipyrromethane unit prior to the oxidative coupling reaction. The optical absorption, emission characteristics, and the quantum yield of the smaragdyrin conjugates depends on the nature of the substituent, nature of linker group, and the spacer length. Theoretical studies at the DFT level suggest high delocalization of electrons confined to only four of the five available heterocyclic rings for the free bases. However, upon Rh(I) metalation, the pi-electron delocalization is extended to all the heterocyclic rings. The two-photon absorption cross section (TPA) values sigma(2) measured through the open aperture Z-scan method, increases linearly with enhanced pi-electron delocalization for the smaragdyrins containing phenylacetylene substituents. The meta branching of substituents decreases sigma(2) values. Introduction of Rh(I) to the smaragdyrin cavity enhances the sigma(2) values by about 3-10 orders of magnitude, attributed to the increased aromatic character upon Rh(I) insertion. The calculated molecular electrostatic potential (MESP) and harmonic oscillator model of aromaticity (HOMA) for the free bases and the Rh(I) derivatives justifies such a conclusion. A linear correlation observed for the second oxidation potential of Rh(I) derivatives and corresponding free bases also support the increased aromaticity upon Rh(I) insertion. The electrochemical data for ferrocene-containing smaragdyrins reveal easier ring oxidation by about 50-130 mV and harder ferrocene oxidation by 40-180 mV suggesting electron-donating nature of the ferrocene upon linking with the smaragdyrin system. The TPA cross section value of 88782 GM observed for 5g represents one of the highest values known for a metalloexpanded porphyrin derivative.

Acetylene↗
PubMed2006

The 'scrubbed surgeon' in robotic surgery.

One of the principal reasons for the rapid progress of robotic surgery has been its advantage in allowing laparoscopy naïve surgeons to offer minimal access surgery to their patients. While this may continue to be an advantage of this modality, it has to be remembered that this has often been possible primarily due to the availability of an assistant who has at least basic laparoscopy skills that permit the performance of critical patient side tasks. We review the literature on the role of the assistant or the 'scrubbed surgeon' in robotic surgery and discuss the advantages of a properly trained assistant in a developing and established robotic surgery program.

Clinical Competence↗
PubMed2006

Correlation between metabolite ratios and ADC values of prostate in men with increased PSA level.

Proton magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI) were carried out in men with increased prostate-specific antigen (PSA) level. Forty subjects [controls (Group I) and patients (Groups II and III with PSA >20 and 4-20 ng/ml, respectively)] were investigated using endorectal coil at 1.5 T prior to transrectal ultrasound (TRUS)-guided biopsy. Metabolite ratio [citrate/(choline+creatine)] and apparent diffusion coefficient (ADC) were calculated for identical voxels. In patients, voxels that showed lower metabolite ratio showed reduced ADC in the peripheral zone (PZ) of the prostate, and voxels with increased metabolite ratio showed higher ADC. Metabolite ratios were used to predict areas of malignancy if the ratio was <1.4 and if ADC value was <1.17 x 10(-3) mm(2)/s. Patients in Group II had lower metabolite ratio and ADC in the PZ compared to controls and Group III. All 13 were positive for malignancy in MR, while 12 of 13 were positive on TRUS-guided sextant biopsy. In Group III, certain voxels of PZ that showed reduced metabolite ratio also showed lower ADC. A positive correlation was observed between metabolite ratio and ADC. MR predicted areas of malignancy in PZ in 15 of 20 patients; however, only six were positive on TRUS-guided biopsy perhaps due to high false-negative rate of TRUS-guided biopsy. Results show positive correlation between MRSI and DWI and their potential in detection of malignancy, thereby improving the diagnosis especially in patients with PSA level of 4-20 ng/ml.

Aged↗
PubMed2006

Comparison of NMP22 BladderChek test and urine cytology for the detection of recurrent bladder cancer.

OBJECTIVE: To assess the clinical performance of the NMP22 BladderChek test, which is a qualitative test, and to compare it with voided urine cytology for the detection of recurrent bladder cancer. We also evaluated whether cystoscopy can be omitted from the surveillance protocol by combining the two tests. METHODS: A total of 131 patients with a history of superficial transitional cell carcinoma of the bladder provided urine samples before a cystoscopic examination. Urine samples were assayed for the presence of NMP22 using the NMP22 BladderChek test and cytology was performed by a cytopathologist. Selected patients underwent a biopsy, with appropriate additional therapy. Results of the two tests were compared with that the results of cystoscopy, which was retained as the gold standard. For positive biopsies, the results of the NMP22 test and cytology were also correlated with the tumor stage and grade. RESULTS: Of the 46 recurrences detected by cystoscopy, the NMP22 test was positive in 39 cases and cytology in 19 cases. The sensitivity of the NMP22 test was 85%, which was significantly greater than that of cytology (41%). In particular, for low-risk tumors it was eight times more sensitive than cytology. The specificities of the NMP22 test and cytology were 77 and 96%, respectively. Combining the two tests increased overall sensitivity to 91%. However, 9% of the tumors were still not detected. CONCLUSION: The NMP22 BladderChek test is an in vitro qualitative test that is easily available and cheap; it can be performed by a urologist in the office and results can be interpreted within 30 min. The NMP22 test is superior to cytology for all grades and stages in the detection of recurrence in patients with a history of superficial bladder cancer. Our study indicates that the NMP22 test can be used as a substitute for urine cytology. The NMP22 test cannot replace cystoscopy, but it can be used as an adjunct to cystoscopy in the surveillance protocol for patients with superficial bladder cancer.

Adult↗
PubMed2006

Depression in mild cognitive impairment in a community sample of individuals 60-64 years old.

OBJECTIVE: This cross-sectional study examined the prevalence and characteristics of depression in subjects with mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health Through Life 60+ (PATH 60+) Project. METHOD: A total of 2551 community-dwelling individuals in the age range 60-64 years were recruited randomly through the electoral roll. They were screened using a short cognitive battery and those who screened positive underwent detailed medical and neuropsychological assessments. There were 29 subjects who fulfilled the Mayo Clinic criteria for MCI and these were compared to 520 controls. Subjects were evaluated for depression symptoms and DSM-IV major and minor depression syndromes. RESULTS: Subjects with MCI had more minor depression and higher scores on a symptom scale. However, a multivariate examination of specific symptoms showed that the differences were confined to only two motivation-related symptoms ("felt slowed up" and "little interest or pleasure"). CONCLUSION: Motivation-related depressive symptoms are more relevant in subjects with MCI than mood-related symptoms.

Australia↗
PubMed2006

Hormone replacement therapy, brain volumes and white matter in postmenopausal women aged 60-64 years.

Research on the structural and functional effects of hormone replacement therapy on the brain has produced inconsistent results. This paper reports on cross-sectional associations between hormone replacement therapy use and volumes of brain structures measured using magnetic resonance imaging in 213 postmenopausal women aged 60-64 years recruited from a large population study. Of these, 64 were current hormone replacement therapy users, 69 previous users and 80 had never used hormone replacement therapy. No differences were observed between groups in total grey matter, white matter, hippocampal or amygdalar volumes, severity or volume of white matter hyperintensities, or in different measures of brain atrophy. While acknowledging the limitations of a cross-sectional study, the results argue against hormone replacement therapy being protective against brain changes associated with ageing in women in their early 60s.

Brain↗
PubMed2006

Drug therapy for idiopathic male infertility: rationale versus evidence.

PURPOSE: About half of all infertile men who seek treatment have no specific cause that can be determined for the seminal abnormality. These men are often subject to a number of medical therapies with doubtful efficacy. We reviewed the rationale on which these therapies are advised and determined whether sufficient medical evidence exists to justify their use. MATERIALS AND METHODS: A literature search was performed using MEDLINE/PubMed, focusing on publications of the last 20 years of drug therapies for idiopathic male factor infertility. Therapies for specific abnormalities such as hypogonadism were excluded. Basic science, in vitro and animal studies suggesting the mechanism of action for male infertility were evaluated as the rationale part of the review, while controlled and uncontrolled human clinical trials were reviewed as evidence for drug use. RESULTS: There is no evidence in support of androgens and gonadotropins for enhancing male fertility. These agents may instead act as contraceptives with significant side effects. There is insufficient evidence regarding the role of antiestrogens, aromatase inhibitors and antioxidants. No drug therapy has proved to be clearly beneficial for idiopathic oligoasthenoteratospermia. CONCLUSIONS: Drug therapy for idiopathic male infertility is at best empirical. There is no clear benefit of using any medication in these patients. Moreover, androgens should not be used because they may actually suppress spermatogenesis.

Antioxidants↗
PubMed2006

Reconstructive surgery for the management of genitourinary tuberculosis: a single center experience.

PURPOSE: We evaluated the role of surgery for genitourinary tuberculosis with special emphasis on reconstructive procedures. MATERIALS AND METHODS: Case records of 241 patients with genitourinary tuberculosis who underwent surgery at our center during a period of 17 years were reviewed. Clinical features, organ involvement, investigations, treatment and outcome of therapy were studied. RESULTS: There were 129 males and 112 females with a mean age of 34.6 years. The most common presentation was irritative voiding symptoms. Azotemia was seen in 54 (22.4%) cases. The most commonly involved organ was the kidney in 130 (53.94%) cases. Preoperative bacteriologic diagnosis was confirmed in 70 (29%) cases. All patients received antitubercular drug therapy for 9 months. A total of 248 procedures, including 33 endoscopic, 87 ablative and 128 reconstructive, were performed with some patients requiring more than 1 procedure. Early complications, which mainly involved the bowel, were seen in 19 (7.88%) cases. Bacteriologic cure was achieved in all culture positive cases. Renal functional parameters stabilized or improved in 44 of 54 patients (81.5%) in whom they were deranged at presentation. CONCLUSIONS: Genitourinary tuberculosis is common in developing countries. Diagnosis is often delayed because of late presentation and many patients present with cicatrization sequelae. A combination of antitubercular drug therapy and judicious surgery achieves satisfactory results in the majority of cases. With improved antitubercular drug therapy and experience with the use of bowel segments in the urinary tract, more reconstructive procedures are being performed with satisfactory outcomes. In patients who undergo reconstructive procedures, a rigorous and prolonged followup is necessary.

Adolescent↗
PubMed2006

Beware! Fungal urosepsis may follow endoscopic intervention for prolonged indwelling ureteral stent.

We present a 38-year-old lady with a prolonged indwelling ureteral stent that had been placed for pain relief after development of Steinstrasse following extracorporeal lithotripsy for a 2.5-cm left renal calculus. The patient developed candidal urosepsis within 6 hours after ureteroscopy and percutaneous nephrolithotomy (PCNL) for the removal of residual fragments. She subsequently recovered on systemic antifungal therapy in the form of intravenous amphotericin B and achieved complete stone clearance after repeat ureteroscopy and PCNL. Fungal urosepsis is known to complicate the postoperative course in chronically debilitated patients with poor nutritional status or those with diabetes or other significant comorbities. To our knowledge, this is the first reported case of a patient with no significant comorbities developing fungal urosepsis after endoscopic intervention for a long-term indwelling ureteral stent.

Adult↗
PubMed2006

Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing benign prostatic hyperplasia of >40 g.

OBJECTIVES: To compare the safety and efficacy of two alternatives for surgically treating symptomatic benign prostatic hyperplasia (BPH), i.e. transurethral vapour resection of the prostate (TUVRP) and holmium laser enucleation of the prostate (HOLEP), with transurethral resection of the prostate (TURP), the standard surgical therapy, as treating large prostates is associated with greater morbidity, and to date there is no simultaneous comparison of these three methods. PATIENTS AND METHODS: We prospectively randomized 150 patients (50 in each group) with BPH and glands of >40 g to undergo either TURP, TUVRP or HOLEP. The evaluation before treatment included urine culture, serum prostate specific antigen (PSA) level estimation, the International Prostate Symptom Score (IPSS), peak urinary flow rate (Q(max)), and transabdominal ultrasonography to estimate prostate size and postvoid urine residue (PVR). The operative duration, blood loss, resected tissue weight, change in levels of haemoglobin and serum sodium, nursing contact time, duration of catheterization, and complications were noted. After surgery patients were reassessed for the IPSS, Q(max) and PVR at 6 months and 1 year. RESULTS: The patients in all three groups had comparable characteristics before surgery. The mean operating duration and intraoperative irrigant used for TUVRP was less than for HOLEP or TURP, and blood loss with HOLEP and TUVRP was less than with TURP (all P < 0.001). Postoperative irrigation, nursing contact time, and catheter duration were significantly less for HOLEP than TURP or TUVRP, and for TUVRP than TURP. At follow-up, patients in all groups had a significant improvement from baseline in IPSS, Q(max,) and PVR, but the differences between the groups were not significant at 6 months or 1 year. CONCLUSIONS: HOLEP and TUVRP are both acceptable alternatives to TURP for treating large prostate glands, with less perioperative morbidity and comparable efficacy at 6 months and 1 year.

Adult↗