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Biomedical subjects

A Kurup

Publications and source records attributed to A Kurup.

At least 19 recordsLinked to original sources

Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan.

Capsular serotypes, magA, and rmpA have been documented in high prevalence for Klebsiella pneumoniae liver abscess. To investigate the regional difference and the correlation of capsular serotype, magA, and rmpA with virulence, 73 isolates were collected in Singapore and Taiwan. Capsular serotypes were determined by countercurrent immunoelectrophoresis, the presence of magA and rmpA was determined by PCR, and virulence was determined by phagocytosis and mouse inoculation. Isolates from Singapore were similar to those from Taiwan in genomic heterogeneity, prevalence of serotype, and the presence of magA and rmpA. The most common serotype was K1 (34/73; 46.6%), followed by K2 (15/73; 20.5%). magA was restricted to serotype K1. All K1 or K2 isolates and 66.7% (16/24) of isolates that were neither serotype K1 nor serotype K2 (non-K1/K2) carried rmpA. Serotype K1 or K2 isolates demonstrated significantly more phagocytic resistance and virulence than did rmpA-positive and -negative groups of non-K1/K2 isolates. In the non-K1/K2 group, the virulence profiles of rmpA-positive strains from Taiwan and Singapore were different by phagocytosis assay and in the mouse model, indicating that factors other than rmpA contributed to virulence. The characteristics of K. pneumoniae liver abscess in Singapore and Taiwan are similar. Capsular serotype K1 or K2 plays a more important role than magA and rmpA in determining virulence in K. pneumoniae liver abscess.

Animals↗

Outpatient parenteral antibiotic therapy in Singapore.

Outpatient parenteral antibiotic therapy (OPAT) remains in its infancy in Singapore, with the first patients enrolled 4 years ago. Singapore's three largest hospitals, with over 3000 inpatient beds, now have designated and approved OPAT services. This study reviews the demographic, clinical and cost data of all patients enrolled in 2005 to facilitate benchmarking between services in Singapore and abroad and also to identify common needs for further development. In 2005, 225 OPAT enrollments in 208 different patients resulted in 4050 days of OPAT care. Orthopaedic diagnoses constituted 40% of admissions. Vancomycin was the most frequently used antibiotic (34%). The re-admission rate was 8.9%, but complications of OPAT care were only occasionally implicated. An estimated $207,200 was saved by patients despite there being significant financial disincentives to subsidised patients. OPAT is a safe, cost-efficient system that is becoming increasingly accepted in Singapore by patients, clinicians and management. Our three services have evolved independently into very similar practices. There is potential for further innovation, including outreach and carer-delivered dosing. However, major financial disincentives require review.

Adolescent↗

Recombinant human angiostatin (rhAngiostatin) in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer: a phase II study from Indiana University.

BACKGROUND: Recombinant human angiostatin (rhAngiostatin) functions as a potent inhibitor of angiogenesis. This study combined rhAngiostatin with a standard chemotherapy regimen in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients had chemotherapy-naïve stage IIIB (with pleural effusion) or IV NSCLC, performance status (PS) 0 or 1, no history of bleeding, brain metastasis or requirements for anti-coagulation. Patients received carboplatin (AUC 5) intravenously and paclitaxel (175 mg/m2) intravenously day 1 + subcutaneous rhAngiostatin at either 15 mg or 60 mg twice daily. Cycles were repeated every 3 weeks, for up to six cycles. Patients without progression after completing at least four cycles were continued on maintenance rhAngiostatin until disease progression. RESULTS: Patient characteristics (n = 24) were: 16 males, median age 66 years (range 45-78), 54% PS 1, 83.3% stage IV and 62.5% adenocarcinoma. Grade 3/4 toxicities included: fatigue 47.8%, neutropenia 39.1%, dyspnea 39.1%, vascular 26.1% and infection 17.4%. The overall response rate was 39.1%, 39.1% stable disease and 21.7% progressive disease. Median time to progression was 144 days, and 1-year survival was 45.8%. CONCLUSIONS: rhAngiostatin in combination with paclitaxel and carboplatin is feasible and results in a high disease control rate in patients with advanced NSCLC.

Aged↗

Cavitating cryptococcal pneumonia in the immunocompetent host.

INTRODUCTION: Isolated cryptococcal pneumonia in the immunocompetent host is a rare infection. Indications for treatment and its duration are currently not defined. CLINICAL PICTURE: Three patients presented with cavitating cryptococcal pneumonia. TREATMENT: They were treated with oral fluconazole. OUTCOME: Improvement was evident clinically, radiologically and serologically. Fluconazole was continued until serum cryptococcal antigen (SCA) levels were negative in our patients as they had manifestations such as haemoptysis, cavitating or multi-lobar pneumonia and relatively high antigen levels, suggesting potentially serious disease. CONCLUSIONS: Fluconazole is effective and safe for the treatment of cryptococcal pneumonia in the immunocompetent host. Although the role of monitoring SCA levels in the immunocompetent host is currently unclear, it may be an indication of infective burden and the benefits of longer treatment seem to outweigh the risks.

Adult↗

Early predictors of mortality in pneumococcal bacteraemia.

INTRODUCTION: Streptococcus pneumoniae bacteraemia is associated with significant mortality rates worldwide. The purpose of this study is to identify risk factors for predicting mortality in patients with S. pneumoniae bacteraemia. MATERIALS AND METHODS: A retrospective cohort study was carried out in a university-affiliated acute tertiary care hospital in Singapore. Thirty-eight patients with blood cultures positive for Streptococcus pneumoniae over a 2-year period from January 2000 to December 2001 were recruited for the study. RESULTS: The records of patients admitted to hospital with blood cultures positive for S. pneumoniae between January 2000 and December 2001 were reviewed. Thirty-eight patients were found positive for S. pneumonia; this included 31 men (81.6%) and 7 women (18.4%) between the ages of 14 years and 90 years. Of this, 7 patients (18.4%) required admission to the intensive care unit, 5 of whom required mechanical ventilation. The factors that predicted mortality were the presence of septic shock (P <0.005), leukopenia or leukocytosis (P <0.005), the presence of an underlying malignancy (P = 0.008), anaemia (P = 0.025) and the presence of a high anion gap (P = 0.047) on admission. CONCLUSION: Of all the risk factors observed, those that predicted mortality in patients on initial presentation of S. pneumoniae bacteraemia were the presence of septic shock, leukopenia or leukocytosis, anaemia, a raised anion gap and the presence of an underlying malignancy.

Adolescent↗

Recurrent necrotizing fasciitis caused by methicillin-resistant Staphylococcus aureus.

Reported here is a rare case of recurrent necrotizing fasciitis due to methicillin-resistant Staphylococcus aureus (MRSA). A 46-year-old female with poorly controlled diabetes and chronic ingestion of steroid-containing medications was admitted for treatment of necrotizing fasciitis of the right thigh. Three months following hospital discharge she was readmitted with necrotizing fasciitis of the left hand. On both occasions, MRSA was isolated from tissue cultures obtained during surgical debridement. Patients who develop necrotizing fasciitis are predisposed to severe soft tissue infections due to associated comorbid conditions such as diabetes mellitus. Recurrent soft tissue infection in a patient with previous MRSA-related necrotizing fasciitis should therefore be treated with a high index of suspicion.

Adult↗

Four cases of necrotizing fasciitis caused by Klebsiella species.

Presented here are four cases of necrotizing fasciitis caused by Klebsiella spp. that were treated at one hospital over a 2-year period. Klebsiella necrotizing fasciitis can occur via direct inoculation, local trauma or, more commonly, hematogenous spread from other septic foci. Early, aggressive, surgical debridement and appropriate antimicrobial treatment are the cornerstones of treatment for this condition. Necrotizing fasciitis due to Klebsiella spp. is unique in that it is commonly associated with multiple septic foci. While liver abscesses and endogenous endophthalmitis are better-known associations of disseminated Klebsiella infection, necrotizing fasciitis is increasingly recognized as one of the manifestations of this syndrome. When treating Klebsiella necrotizing fasciitis, awareness of the potential for multiorgan involvement should prompt a thorough search for associated foci of infection.

Adult↗

Management of inpatients exposed to an outbreak of severe acute respiratory syndrome (SARS).

This is a prospective observational study of a cohort of inpatients exposed to a severe acute respiratory syndrome (SARS) outbreak. Strict infection control policies were instituted. The 70 patients exposed to the SARS outbreak were isolated from the rest of the hospital. They were triaged, quarantined and cohorted in three open plan wards. Selective isolation was carried out immediately when symptoms and signs suspicious of SARS manifested clinically. The patients' ages ranged from 21 to 90 years and 56% had surgery before the quarantine. Sixteen patients with unexplained fever during the period of quarantine were isolated, seven of whom were eventually diagnosed with probable SARS. The crude incidence of SARS in our cohort was 10%. The SARS case fatality was 14%. No secondary transmission of the SARS virus within the cohort was observed. Strict infection control, together with appropriate triaging, cohorting and selective isolation, is an effective and practical model of intervention in cohorts exposed to a SARS outbreak. Such a management strategy eases the logistic constraints imposed by demands for large numbers of isolation facilities in the face of a massive outbreak.

Adult↗

Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation.

Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation.

Adolescent↗

Searching for allosteric effects via QSARs.

A study of our database of 7,000 QSARs involving chemical-biological interaction uncovered 11 examples where the QSARs all contain inverted parabolas based on molecular refractivity. That is, biological activity first decreases with increase in MR and then increases. Two of the examples are for enzymes: cyclooxygenase and trypsin. The others are for various receptors. The results seem to be best rationalized by the larger compounds inducing a change in a receptor unit that allows for a new mode of interaction.

Allosteric Regulation↗

QSAR of anticancer compounds. Bis(11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides), bis(phenazine-1-carboxamides), and bis(naphthalimides).

QSAR have been developed for the anticancer activity (growth inhibition) of various tumor cells by bis(11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides), bis(phenazine-1-carboxamides), and bis(naphthalimides). Of the seven QSAR, positive hydrophobic interactions are found in only two examples: bis(naphthalimides) versus human colon cancer cells. This is consistent with other QSAR of anticancer compounds where hydrophobic interactions are found to be unimportant.

1-Naphthylamine↗

Possible allosteric effects in anticancer compounds.

We have found in this report, and an earlier one, that in a variety of instances an inverted parabolic relationship between biological activity and CMR or logP is observed. That is, activity first decreases as CMR or logP increases and then turns about and increases. This could be attributed to the ligands causing a change in the receptor structure. The present report considers QSAR for a variety of resistant and sensitive cancer cells.

Antineoplastic Agents↗

Comparative QSAR: on the toxicology of the phenolic OH moiety.

In this report we consider the effect of substituents on phenol toxicity and show how the parameters used in Quantitative Structure-Activity Relationships (QSAR) can be used to draw mechanistic inferences of value in understanding the reasons behind the various types of toxicity. In particular, we are interested in gaining clearer insight into mechanisms via the Hammett-type parameters sigma, sigma(-), sigma(+) and octanol/water parti tion coefficients. Particular attention is given to the role of radical reactions and their role in attacking DNA to cause cancer or estrogenic toxicity.

Animals↗