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Biomedical subjects

P Ray

Publications and source records attributed to P Ray.

At least 19 recordsLinked to original sources

The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia.

The dual 5alpha-reductase inhibitor, dutasteride has been shown to suppress serum dihydrotestosterone (DHT) by >90%. In the present study, the effect of dutasteride 0.5 mg/day on intraprostatic DHT levels was investigated. In this multicenter, double-blind trial, 43 men with benign prostatic hyperplasia (BPH) scheduled to undergo transurethral resection of the prostate (TURP) were randomized to receive dutasteride, 0.5 mg/day or placebo for 3 months before surgery. Intraprostatic DHT, testosterone and dutasteride levels were determined at the time of TURP. Changes in serum DHT and testosterone from baseline, and both serum and intraprostatic dutasteride levels at the time of TURP were also assessed. Dutasteride reduced intraprostatic DHT by 94% relative to placebo (P<0.001); the adjusted mean intraprostatic DHT concentration was 3.23 and 0.209 ng/g in the placebo and dutasteride groups, respectively. In the dutasteride group, serum DHT was reduced from baseline by 93% at month 3, a significantly greater reduction (P<0.001) than the 15% decrease observed in the placebo group. There was a reciprocal increase in intraprostatic testosterone but the level of intraprostatic testosterone in the dutasteride group tended to be lower than the intraprostatic DHT level in the placebo group (P=0.06). Significant intraprostatic DHT suppression was achieved in all subjects who received dutasteride, regardless of the level of intraprostatic dutasteride. There was a strong positive correlation between serum and intraprostatic dutasteride concentrations (R(2)=0.73). After 3 months of treatment, dutasteride 0.5 mg/day provided near-complete suppression of both intraprostatic and serum DHT in men with BPH.

Aged↗

Sudden infant death in a patient with FGFR3 P250R mutation.

P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities. We report a family with this mutation associated with sudden death in an affected newborn, most probably due to upper airway obstruction.

Adult↗

Study of nosocomial primary bloodstream infections in a pediatric intensive care unit.

Bloodstream infections (BSI) are the commonest cause of nosocomial infections (NI) in PICU. Knowledge about their magnitude, risk factors and outcome are important in devising appropriate prevention and control measures. Our objective was to study the incidence, etiology, risk factors and outcome of primary BSI in PICU. A prospective cohort of 285 patients consecutively admitted to PICU from July 2003-04, having a stay of >48 h, were enrolled and monitored for BSI till discharge from ICU or death. Primary BSI was defined as per CDC criteria 1988. Data of patients with BSI was compared with those without BSI with respect to demographic details, PRISM III, primary diagnosis, nutritional status, device utilization and invasive procedures to identify risk factors for BSI. Variables significant on univariate analysis were subjected to multiple logistic regression analysis. Outcome was measured as length of PICU stay (LOS) and survival or death. There were 116 episodes of primary BSI in 86 (30%) patients; the incidence being 31.2 episodes/1000 patient days. The mean age of the patients with BSI was 3.7 +/- 3.5 years. Predominant isolates were Gram-negative (53.5%); Klebsiella pneumoniae (n = 21) being the commonest. Staphylococcus aureus (n = 18) was the most common Gram-positive organism. Seven of the 9 (77.8%) yeast isolates were Candida tropicalis. Younger age, higher PRISM III, lower hemoglobin, pre-existing infection, higher frequency and duration of device utilization (CVC, urinary catheter, endotracheal tube, mechanical ventilation) were significant risk factors on univariate analysis. On multiple logistic regressions, hemoglobin (OR 1.24, 95% CI 1.1-1.4, p = 0.002) duration of urinary catheter (OR 0.91, 95% CI 0.84-0.98, p = 0.015) and pre-existing infection (OR 0.46, 95% CI 0.23-0.93, p = 0.03) were independent risk factors for primary BSI. The median LOS was significantly longer in patients with BSI compared to those without (16 vs. 7 days, p = 0.0001) 47% of patients with BSI died as compared to 26% deaths in the whole cohort (p = 0.002). Just over half the cases of BSI in our PICU were caused by Gram-negative bacteria. Lower hemoglobin, pre-existing infection and prolonged duration of urinary catheter were independent risk factors identified on multivariate analysis. BSI was associated with significantly higher mortality and longer stay in our PICU.

Bacterial Infections↗

Clinical characteristics and outcomes of empyema thoracis in 117 patients: a comparative analysis of tuberculous vs. non-tuberculous aetiologies.

BACKGROUND: Empyema thoracis remains a major problem in developing countries. Clinical outcomes in tuberculous empyema are generally believed to be worse than in non-tuberculous aetiologies because of the presence of concomitant fibrocavitary parenchymal disease, frequent bronchopleural fistulae and poor general condition of patients. We performed a prospective study over a 2-year period with the objective of comparing the clinical characteristics and outcomes of patients with tuberculous vs. non-tuberculous empyema. METHODS: Prospective study of all cases of non-surgical thoracic empyema seen at a tertiary care centre in North India over a 2-year period. A comparative analysis of clinical characteristics, treatment modalities and outcomes of patients with tuberculous vs. non-tuberculous empyema was carried out. Factors associated with poor outcomes were analysed using multivariate logistic regression. RESULTS: One hundred and seventeen cases of empyema were seen in the study period of which 95 had non-tuberculous and 41 had tuberculous empyema. Malnutrition and bronchopleural fistulae (BPF) were more common and duration of symptoms longer in the tuberculous empyema group. Time to resolution of fever, duration of pleural drainage and pleural thickening >2 cm were significantly greater as well. Eight (10.5%) patients with non-tuberculous empyema and four (9.8%) with tuberculous empyema succumbed. Presence of a BPF was significantly associated with poor outcomes on multivariate logistic regression analysis. CONCLUSIONS: Tuberculous empyema remains a common cause of thoracic empyema in India though it ranked second amongst all causes of empyema after community acquired lung infections in this study. Tuberculous empyema is associated with longer duration of symptoms, greater duration of pleural drainage and more residual pleural fibrosis.

Adolescent↗

Efficacy and tolerability of the dual 5alpha-reductase inhibitor, dutasteride, in the treatment of benign prostatic hyperplasia in African-American men.

The efficacy and tolerability of dutasteride (0.5 mg daily for 2 years) in African-Americans (n=161), compared with Caucasians (n=3961), was assessed in a post hoc analysis of data from three Phase III clinical trials. Dutasteride significantly reduced serum dihydrotestosterone levels by >90% and significantly improved subjective (symptom score) and objective (prostate volume, peak urinary flow rate, risk of benign prostatic hyperplasia-related surgery and acute urinary retention) outcomes in both African-Americans and Caucasians. For all efficacy measures, there was no statistically significant treatment-by-race interaction and dutasteride was well tolerated in both racial groups. Therefore, dutasteride demonstrated similar efficacy and safety profiles in African-Americans and Caucasians.

5-alpha Reductase Inhibitors↗

[Usefulness of B-type natriuretic peptide in emergency medicine].

OBJECTIVES: Acute dyspnea is frequent in emergency medicine. The B-type natriuretic peptide is a polypeptide, released by ventricular myocytes directly proportional to wall tension, for lowering renin-angiotensin-aldosterone activation. Conversely, NT-proBNP has no physiological activity. BNP and NT-proBNP concentration closely correlate to various indicators of heart failure. CURRENT KNOWLEDGE AND KEY POINTS: Numerous studies have demonstrated high usefulness of BNP and NT-proBNP to diagnose heart failure, which is the main cause of acute dyspnea in emergency medicine. The diagnostic accuracy of BNP and NT-proBNP seems similar, and is higher than that of the emergency physician. Bedside dosages are now available, with high sensibility and specificity for the diagnosis of heart failure. For BNP, threshold value is ranging from 100 to 300 pg/ml in patients aged over 65 years; for NT-proBNP the threshold value is 1000 to 2000 pg/ml in elderly patients. Briefly, heart failure is unlikely when BNP is below 100 pg/ml (NT-proBNP<500 pg/ml), and very likely when BNP is higher than 400 pg/ml (or NT-proBNP>2000 pg/ml). FUTURE PROJECTS: Early rapid measurement of BNP could improved the evaluation and treatment of patients with acute dyspnea and reduce the total cost of treatment.

Acute Disease↗

[Preimplantation genetic diagnosis (PGD): results from a Parisian center].

OBJECTIVE: To report the results of preimplantation genetic diagnosis (PGD) cycles performed in our unit from 2000 to 2004. Materials and methods. One hundred and seventy-one couples were enrolled in the PGD program over this period. The collected oocytes were inseminated by intracytoplasmic sperm injection (ICSI). The resulting embryos were biopsied on the third day of development and the genetic analysis was performed on the same day. Embryo transfers were carried out on the fourth day. RESULTS: The 416 stimulation cycles started yielded 280 oocyte pick-ups, 3506 oocytes retrieved, of which 2966 were suitable for ICSI. Among the 1982 embryos obtained, 1337 embryos were biopsied and genetic diagnosis was performed for 1083 (81%) of them. 381 embryos were transferred during the course of 189 transfer procedures. There were 51 clinical and 46 ongoing (35 single, 11 twin) pregnancies. In addition, 25 frozen embryo replacement cycles were initiated, leading to 6 embryo transfers and 1 ongoing pregnancy. A total of 58 unaffected children were born. CONCLUSION: PGD has gained a place among the choices offered to couples at risk of transmission of a serious and incurable genetic disease. It might be a realistic alternative to prenatal diagnosis for patients carrier of chromosomal rearrangements, single gene defects, X-linked disesases or mitochondrial DNA disorders.

Adult↗

Polymerase chain reaction for early diagnosis of post-operative fungal endophthalmitis.

BACKGROUND AND OBJECTIVES: Fungal endophthalmitis is a devastating form of ocular infection and postoperative endophthalmitis following cataract surgery is the commonest form of such infection. Early diagnosis is very important for effective management of these patients. As conventional techniques take longer time and lacks sensitivity, polymerase chain reaction (PCR) for detection of fungal DNA was evaluated for early diagnosis of postoperative fungal endophthalmitis. METHODS: Fifty consecutive patients with postoperative endophthalmitis (excluding proven bacterial endophthalmitis) and 25 individuals undergoing pars plana vitrectomy (PPV) of non infectious aetiologies (control group) were included in the study. Aqueous/vitreous fluids, collected from these patients, were evaluated by conventional methods including direct microscopy and culture, and by PCR for detection of fungal DNA using panfungal primers (ITS1 and ITS4) for diagnosis of fungal aetiology. RESULTS: None of the controls were positive for fungal aetiology by microscopy, culture or PCR. Four patients were positive for fungal endophthalmitis by conventional method of diagnosis. PCR based method detected fungal DNA in three of these patients and in three additional patients who were negative on microscopy and culture. All six patients, who were positive for PCR, showed clinical improvement after full course of antifungal therapy. INTERPRETATION AND CONCLUSION: Compared to the conventional technique, PCR for detection of fungal DNA was found to be a rapid and more sensitive method in the early diagnosis of postoperative fungal endophthalmitis.

Adolescent↗

Coordinated expression and immunogenicity of an outer membrane protein from Salmonella enterica serovar Typhi under iron limitation, oxidative stress and anaerobic conditions.

Successful pathogens overcome the environmental stresses by the coordinated expression of various genes and eventually proteins. Since, the surface of the microbe is likely to come in contact with the host initially, an attempt was made to identify the outer membrane proteins (OMPs), if any, which may get expressed under more than one environmental conditions simulating the in vivo ones. In the present study, Salmonella enterica serovar Typhi was grown under iron-limited, oxidative stress as well as anaerobic conditions and the OMP profiles were compared. A 69 kDa OMP was found to express with enhanced intensity under the selected stress conditions in comparison to normal conditions. The phenotypic similarity among the proteins was assessed on the basis of their molecular weight, cross reactivity and HPLC. The protein expressed under oxidative stress and anaerobic conditions reacted with the antibodies raised against iron-regulated outer membrane protein (IROMP), indicating the sharing of at least some of the epitopes. A single peak observed after subjecting the pooled 69 kDa protein sample and appearance of a single band on SDS-PAGE thereafter, confirmed the purity and phenotypic similarity of the 69 kDa OMP. Reactivity of pooled 69 kDa protein with 85% of sera from typhoid patients revealed the in vivo expression of this protein. The results of this study indicate the coordination of this phenotype under iron stress, oxidative stress and anaerobic conditions. In view of the expression of the 69 kDa protein under the selected stress conditions and their in vivo immunogenicity, these findings may be relevant for the better understanding of the host-microbe interactions and for the further development of diagnostic and preventive strategies.

Animals↗

[The Paris experience in preimplantation genetic diagnosis: evaluation after the first births].

OBJECTIVE: To report the birth of the first thirteen infants conceived after preimplantation genetic diagnosis (PGD) within the medical assistance federation of Paris. PATIENTS AND METHODS: Fifty-nine couples were enrolled between January 2000 and July 2001. They had a total of 71 oocyte pick-up cycles. The collected oocytes were inseminated by intracytoplasmic sperm injection. The resulting embryos were biopsied on the third day of development and the genetic analysis was performed on the same day. Most of the embryo transfers were carried out on the fourth day. RESULTS: The 71 oocyte pick-up cycles yielded 872 oocytes of which 731 were suitable for intracytoplasmic sperm injection. 421 embryos were biopsied and genetic diagnosis was obtained from 312 (74%) of these. 127 embryos were transferred during the course of 58 transfer procedures. There were 18 biologic and 12 clinical (7 singles, 4 twins and 1 triple) pregnancies. Thirteen infants have been born and 4 are expected. CONCLUSIONS: PGD has gained a place among the choices offered to couples at risk of transmission of a serious and incurable genetic disease.

Blastocyst↗

Gene organization and sequences of pediocin AcH/PA-1 production operons in Pediococcus and Lactobacillus plasmids.

AIMS: To determine the locations and sequences of pediocin AcH production genes in Pediococcus parvulus ATO77 from vegetables, Lactobacillus plantarum WHE92 from Muenster cheese, and a lactose-fermenting isolate Pediococcus pentosaceus S34 from buffalo milk. METHODS AND RESULTS: Plasmid curing, Southern blot hybridization, and DNA sequence analysis indicate that pediocin AcH production genes are encoded by highly similar operons in unique plasmids designated pATO77 from P. parvulus ATO77, pS34 from P. pentosaceus S34, and pWHE92 from Lact. plantarum WHE92. Structure, immunity and secretion system genes are linked together in the operons, and the promoter sequences are the same. The amino acid sequences of the encoded proteins are highly conserved between plasmids. CONCLUSIONS: Pediocin AcH production genes are located within a plasmid-borne operon cassette in all lactic acid bacterial strains examined to date. All four genes needed for production are present within a single plasmid in each strain. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first demonstration that the expression of a class IIa bacteriocin is directed by a common gene cassette that has been disseminated to unique plasmids in different genera of lactic acid bacteria. These plasmids should be useful for expressing pediocin AcH in Pediococcus and Lactobacillus strains used in food production.

Bacteriocins↗

Suction drain tip culture in orthopaedic surgery: a prospective study of 214 clean operations.

We conducted a prospective cohort study in order to determine whether suction drain specimen cultures from orthopaedic surgery predicted an early wound infection. We included 218 consecutive clean orthopaedic operations requiring drains in one unit over a period of 1 year. The suction drain tip, drain fluid and wound discharge specimens were cultured, and the surgical wound was followed up for 3 months. There were six deep and two superficial wound infections. Wound infection was significantly related to positive suction tip culture but not to positive drain fluid culture. Following our methodology for culture, a positive drain tip culture predicts wound infection in 50% and a negative culture virtually excludes the possibility of a deep infection.

Adolescent↗

Recognition and management of maternal cardiac disease in pregnancy.

Heart disease is a leading cause of maternal death. The aim of this study is to review the most common causes of cardiac disease, highlight factors that should be recognized by the clinician, and address recent advances in the anaesthetic management of these patients. Incipient cardiac disease, including peripartum cardiomyopathy, myocardial infarction and aortic dissection, accounts for approximately one in six maternal deaths. The keys to successful diagnosis and management of incipient disease are: a high index of suspicion, particularly in women with known risk factors for cardiovascular disease; a low threshold for radiological investigations; early cardiology input; and invasive monitoring during labour and delivery. Echocardiography is a safe, non-invasive test, under-used in pregnancy. Management of pregnant women with pre-existing cardiac problems should be undertaken by multidisciplinary teams in tertiary centres. In women with pre-existing cardiac disease wishing to proceed to term, cardiac status must be optimized preoperatively and planned elective delivery is preferable. Vaginal delivery is preferable, and with careful incremental regional anaesthesia is safe in most women with cardiac disease. The presence of adequate systems for early detection, appropriate referral to specialist centres, and timely delivery with multidisciplinary support can minimize the serious consequences of poorly controlled heart disease in pregnancy.

Anesthesia, Obstetrical↗

Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer.

PURPOSE: In the prostate testosterone is converted to dihydrotestosterone (DHT) by the enzymes 5alpha-reductase (5alphaR) types 1 and 2 (5alphaR1 and 5alphaR2). Suppression of DHT formation by 5alphaR inhibition may be beneficial in early treatment or prevention of prostate cancer. Although 5alphaR2 is the dominant enzyme in the prostate, evidence indicates that 5alphaR1 may be up-regulated in some prostate cancers. This suggests that dual inhibition of both isoenzymes may be more effective than suppression of 5alphaR2 alone in prostate cancer treatment or prevention. In this short-term pilot study we examined the effect of the dual 5alphaR inhibitor dutasteride on markers of tumor regression. MATERIALS AND METHODS: A total of 46 men with clinically staged T1 or T2 prostate cancer were randomized to receive 5 mg per day of placebo or dutasteride for 6 to 10 weeks before radical prostatectomy. Resected tissues were analyzed to determine the effect of dutasteride on intraprostatic androgen levels, and indices of apoptosis and microvessel density (MVD) in malignant tissue, as well as degree of atrophy in benign tissue. RESULTS: Treatment with dutasteride caused a 97% decrease in intraprostatic DHT and was associated with a trend toward increased apoptosis. In patients receiving dutasteride for 45 days or more, a significant increase in apoptosis and a trend toward decreased MVD in prostate cancer tissue was observed. Dutasteride treatment was also associated with an 18% decrease in mean benign epithelial cell width compared with placebo (p < 0.0001). CONCLUSIONS: In this pilot study dutasteride treatment resulted in almost complete suppression of intraprostatic DHT, increased apoptosis and a trend toward decreased MVD. These findings suggest that short-term treatment with dutasteride can cause regression in some prostate cancers.

5-alpha Reductase Inhibitors↗

Quality assessments of HMO diagnosis databases used to monitor childhood vaccine safety.

OBJECTIVE: To assess the quality of automated diagnoses extracted from medical care databases by the Vaccine Safety Datalink (VSD) study. METHODS: Two methods are used to assess quality of VSD diagnosis data. The first method compares common automated and abstracted diagnostic categories ("outcomes") in 1-2% simple random samples of study populations. The second method estimates positive predictive values of automated diagnosis codes used to identify potential cases of rare conditions (e.g., acute ataxia) for inclusion in nested case-control medical record abstraction studies. RESULTS: There was good agreement (64-68%) between automated and abstracted outcomes in the 1-2% simple random samples at 3 of the 4 VSD sites and poor agreement (44%) at 1 site. Overall at 3 sites, 56% of children with automated cerebella ataxia codes (ICD-9 = 334) and 22% with "lack of coordination" codes (ICD-9 = 781.3) met objective clinical criteria for acute ataxia. CONCLUSIONS: The misclassification error rates for automated screening outcomes substantially reduce the power of screening analyses and limit usefulness of screening analyses to moderate to strong vaccine-outcome associations. Medical record verification of outcomes is needed for definitive assessments.

Child, Preschool↗