Cefpodoxime — utility in respiratory tract infections and typhoid fever

Cefpodoxime is a oral third generation cephalosporin active against most of gram positive and gram negative bacteria except Pseudomonas, B. fragilis and Entrococcous. Clinical studies have confirmed efficacy of cefpodoxime in acute otitis media, sinusitis and tosillopharyngitis. Twice daily administration and safety profile increases compliance and decreases failure rate. It has a role as switch over therapy from intravenous ceftriaxone in serious respiratory tract infections (RTIs). In areas where common respiratory pathogens show decreased sensitivity to penicillins and macrolides cefpodoxime can be used as empirical first line therapy in respiratory tract infections. It seems to be a promising molecule in pediatric typhoid fever because of its excellent activity against Salmonella species but clinical trials are limited.     

Costs of illness due to typhoid fever in an Indian urban slum community: implications for vaccination policy

Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to facilitate the use of available anti-typhoid vaccines in developing countries. This one-year prospective surveillance was carried out in an urban slum community in Delhi, India, to estimate the costs of illness for cases of typhoid fever. Ninety-eight culture-positive typhoid, 31 culture-positive paratyphoid, and 94 culture-negative cases with clinical typhoid syndrome were identified during the surveillance. Estimates of costs of illness were based on data collected through weekly interviews conducted at home for three months following diagnosis. Private costs included the sum of direct medical, direct non-medical, and indirect costs. Non-patient (public) costs included costs of outpatient visits, hospitalizations, laboratory tests, and medicines provided free of charge to the families. The mean cost per episode of blood culture-confirmed typhoid fever was 3,597 Indian Rupees (US$ 1=INR 35.5) (SD 5,833); hospitalization increased the costs by several folds (INR 18,131, SD 11,218, p<0.0001). The private and non-patient costs of illness were similar (INR 1,732, SD 1,589, and INR 1,865, SD 5,154 respectively, p=0.8095). The total private and non-patient ex-ante costs, i.e. expected annual losses for each individual, were higher for children aged 2-5 years (INR 154) than for those aged 5-19 years (INR 32), 0-2 year(s) (INR 25), and 19-40 years (INR 2). The study highlights the need for affordable typhoid vaccines efficacious at 2-5 years of age. Currently-available Vi vaccine is affordable but is unlikely to be efficacious in the first two years of life. Ways must be found to make Vi-conjugate vaccine, which is efficacious at this age, available to children of developing-countries.     

Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

Background  

Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer.     

Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure

OBJECTIVES: This study was designed to determine the relevance of a proposed classification for advanced heart failure (HF). Profiles based on clinical assessment of congestion and perfusion at the time of hospitalization were compared with subsequent outcomes. BACKGROUND: Optimal design of therapy and trials for advanced HF remains limited by the lack of simple clinical profiles to characterize patients. METHODS: Prospective analysis was performed for 452 patients admitted to the cardiomyopathy service at the Brigham and Women's Hospital with a diagnosis of HF. Patients were classified by clinical assessment into four profiles: profile A, patients with no evidence of congestion or hypoperfusion (dry-warm, n = 123); profile B, congestion with adequate perfusion (wet-warm, n = 222); profile C, congestion and hypoperfusion (wet-cold, n = 91); and profile L, hypoperfusion without congestion (dry-cold, n = 16). Other standard predictors of outcome were included and patients were followed for the end points of death (n = 117) and death or urgent transplantation (n = 137) at one year. RESULTS: Survival analysis showed that clinical profiles predict outcomes in HF. Profiles B and C increase the risk of death plus urgent transplantation by univariate (hazard ratio [HR] 1.83, p = 0.02) and multivariate analyses (HR 2.48, p = 0.003). Moreover, clinical profiles add prognostic information even when limited to patients with New York Heart Association (NYHA) class III/IV symptoms (profile B: HR 2.23, p = 0.026; profile C: HR 2.73, p = 0.009). CONCLUSIONS: Simple clinical assessment can be used to define profiles in patients admitted with HF. These profiles predict outcomes and may be used to guide therapy and identify populations for future investigation.     

Immunostimulant principles from Curculigo orchioides

Curculigo orchioides Gaerten belongs to the family Amaryllidaceae. The rhizomes of the plants are used for the treatment of decline in strength, jaundice and asthma. Its methanolic extract has been shown to enhance phagocytic activity of macrophages. Present studies have led to the isolation of two phenolic glycosides and a purified glycoside fraction. These were studied for their effect on macrophage migration index (MMI), haemagglutination (HA) titre, plaque forming cell (PFC), PHA-induced blast transformation of lymphocytes (BTL) and delayed type hypersensitivity (DTH). Significant immunostimulant activity was found in purified glycoside-rich fraction isolated from the ethyl acetate extract. The exact structure of the active glycoside is yet to be determined. The enhancement of HA titre and PFC count on one hand and that of DTH response on the other indicates that glycoside fraction stimulates both humoral and Cell-mediated immune responses. Glycoside fraction stimulates immune response by acting both on macrophages and the lymphocytes.     

Delayed nerve conduction velocities in children with protein-calorie malnutrition.

Protein-calorie malnutrition in human beings and animals affects the myelination and growth of the nervous system. The effects of PCM on the developing nervous system were evaluated by measuring the nerve conduction velocities in 93 (38 marasmus, 13 kwashiorkor, and 42 control) children in ulnar, median, peroneal, and posterior tibial nerves. The children were divided into three age groups: Group I, six to 12 months; Group II, 13 to 24 months; Group III, 25 to 48 months. All 13 children with kwashiorkor demonstrated irritability, delayed milestones, and muscular wasting; and six also had hypoactive muscle reflexes. Conduction velocities were reduced in each type of malnutrition, with statistically significant differences in the three groups of marasmic children and in Group III kwashiorkor children. Children with kwashiorkor in Group II had significantly reduced velocities only in the nerves of the lower extremities. These data suggest PCM, when it occurs during the development of the nervous system, affects myelination of the peripheral nerves.     

Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve biological half-life,brain delivery and efficacy in glioblastoma cells

Noscapine crosses blood–brain-barrier and inhibits proliferation of glioblastoma cells. However, short plasma half-life and rapid elimination necessitate the administration of multiple injections for successive chemotherapy. Noscapine bearing solid lipid nanoparticles, Nos-SLN and poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine, Nos-PEG-SLN of 61.3 ± 9.3-nm and 80.5 ± 8.9-nm containing 80.4 ± 3.2% and 83.6 ± 1.2% of Nos, were constructed. First order kinetic and Higuchi equation were followed to release the Nos at intracellular pH ~ 4.5. Further, a decrease in IC₅₀ (Nos; 40.5 μM > Nos-SLN; 27.2 μM > 20.8 μM) and enhanced subG1 population were observed in U87cells. Plasma half-life was enhanced up to ~ 11-fold and ~ 5-fold by Nos-PEG-SLN and Nos-SLN which significantly (P < 0.05) deposits 400.7 μg/g and 313.1 μg/g of Nos in comparison to 233.2 μg/g by drug solution. This is first report demonstrating a workable approach to regulate the administration of multiple injections of Nos, warranting further in vivo tumor regression study for superior management of brain cancer.From the Clinical EditorThis report describes a possible approach to regulate the administration of multiple injections of Noscapine using solid lipid nanoparticles. The data warrant further in vivo tumor regression studies for optimal management of glioblastoma, a generally very poorly treatable brain cancer.