Human papillomavirus (HPV) quadrivalent recombinant vaccine is a mixture of virus-like particles derived from the L1 capsid proteins of HPV types 6, 11, 16 and 18. It is administered intramuscularly in a three-dose regimen, with the initial injection followed by subsequent doses at months 2 and 6. The vaccine is indicated for use in the prevention of cervical cancer, vulvar and vaginal precancer and cancers, precancerous lesions and genital warts associated with HPV types 6, 11, 16 or 18 infection in adolescents and young women. The quadrivalent vaccine has demonstrated good immunogenicity in young women (16-26 years) and male and female adolescents (aged 9-15 years), inducing high and persistent anti-HPV antibody titres. In a randomised phase III trial designed to bridge efficacy in young women to adolescents (using immunogenicity as a surrogate), the quadrivalent HPV vaccine in adolescents was at least as immunogenic as that in young women. In randomised, double-blind, placebo-controlled trials in >20 000 young women (aged 16-26 years), the vaccine was highly effective in preventing cervical dysplasia of any grade and external genital lesions related to HPV types 6, 11, 16 and 18 infection. These women were followed up for an average of 2 years.black triangle The vaccine was well tolerated, with injection-site reactions and fever being the most common vaccine-related adverse events.

Human papilloma virus is a causative factor in the etiology of cervical cancer with HPV16 being the most prevalent genotype associated with it. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV 16 besides being of phylogenetic importance, are associated with risk of viral persistence and progression. The objective of this multicentric study was to identify HPV-16 E6, E7 and L1 variants prevalent in India and their possible biological effects. Squamous cell cervical cancer biopsies were collected from 6 centres in India and examined for the presence of HPV 16. Variants of HPV-16 were characterized by full length sequence analysis of L1, E6 and E7 genes in 412 samples. Similar distribution of the variants was seen from the different centres/regions, with the European variant E350G being the most prevalent (58%), followed by American Asian variant (11.4%). Fifty six changes were seen in E6 region, 31 being nonsynonymous. The most frequent being L83V (72.3%), Q14H (13.1%) and H78Y (12.1%). Twenty-nine alterations were seen in E7 region, with 12 being nonsynonymous. The most frequent being F57V (9%). L1 region showed 204 changes, of which 67 were nonsynonymous. The most frequent being 448insS (100%), and 465delD (100%), H228D (94%), T292A (85%). The identified variants some new and some already reported can disrupt pentamer formation, transcriptional regulation of the virus, L1 protein interface interaction, B and T cell epitopes, p53 degradation, and thus their distribution is important for development of HPV diagnostics, vaccine, and for therapeutic purpose. ' UICCKey words: cervical cancer; human papilloma virus 16; variants Cervical cancer is the second most predominant cancer worldwide. 1 In India it is the most common cancer amongst women, accounting for 130,000 new cases and more than 70,000 deaths annually. Persistent infection with high risk Human papilloma virus (HPV) is the main aetiological factor in the development of cervical cancer and may depend on HPV genotypes and variants. 2 HPV-16 is the most prevalent genotype associated with cervical carcinomas globally, as well as in Indian women. [3][4][5] This could perhaps be because of differential HPV-16 variant frequency, with certain variants conferring greater oncogenecity. 6,7 The molecular variants or lineages differ in nucleotide sequence by no more than 2% in the coding region and 5% in the noncoding regions of the viral genome with respect to the prototype. 8 Through nucleotide sequence comparisons, it has been found that HPV-16 has evolved along 5 major phylogenetic branches i.e., European, Asian, Asian American, African-1 and African-2. 9 Intratypic variation of HPV-16 has been shown to be an important predictor of progression to clinical relevant cervical lesion. 10 In a cohort study of young women 16 different HPV variants were found, one of which persisted over time, although the other variants were transiently detected. 11 Considerable intratypic diversity of HPV-16 has been reported by other studies based on DNA sequenc...

Imatinib (Gleevec, Glivec) is a synthetic tyrosine kinase inhibitor used in the treatment of chronic myeloid leukaemia (CML). It is specifically designed to inhibit the breakpoint cluster region (BCR)-Abelson (ABL) fusion protein that results from the chromosomal abnormality known as the Philadelphia chromosome. CML is characterised by this abnormality, which leads to abnormalities of the peripheral blood and bone marrow including an increase in the number of granular leukocytes. Imatinib is approved in numerous countries worldwide for the treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase CML, Ph+ accelerated-phase or blast-crisis CML, and in patients with Ph+ chronic-phase CML who have failed to respond to interferon-alpha therapy. It is also indicated in paediatric patients with newly diagnosed Ph+ chronic-phase CML, in accelerated-phase or blast-crisis CML, or in chronic-phase CML after failure of interferon-alpha therapy or when the disease has recurred after haematopoietic stem cell transplantation (HSCT). Approved indications, however, may vary by country. Imatinib is effective and generally well tolerated in patients with Ph+ CML. In patients with newly diagnosed chronic-phase CML, imatinib was more effective than interferon-alpha plus cytarabine in preventing progression of the disease and in achieving haematological and cytogenetic responses. Overall survival rates remain high after 5 years of follow-up, and historical comparisons with other treatments demonstrate improved overall survival with imatinib in the long term. Patients with accelerated-phase or blast-crisis CML, or those who have not responded to prior interferon-alpha therapy also benefit from imatinib treatment. Some patients become resistant or intolerant to imatinib therapy; management strategies to overcome these problems include dosage adjustment, other treatments, or combination therapy with imatinib and other agents. Allogeneic HSCT is currently the only potentially curative treatment, but it is associated with high rates of morbidity and mortality and is not suitable for all patients. The introduction of imatinib has had a marked impact on outcomes in patients with CML. It remains a valuable treatment for all stages of the disease, especially initial treatment of newly diagnosed Ph+ chronic-phase CML, and is endorsed by European and US treatment guidelines as a first-line option.

Palonosetron is a potent and highly selective serotonin 5-HT(3) receptor antagonist that has been evaluated for the prevention of chemotherapy-induced nausea and vomiting. black triangle Intravenously administered palonosetron has a linear pharmacokinetic profile, with a long terminal elimination half-life ( approximate, equals 40 hours) and moderate (62%) plasma protein binding. In two randomised, double-blind trials in 1132 cancer patients receiving moderately emetogenic chemotherapy, intravenous palonosetron 0.25 mg was more effective than intravenous ondansetron 32 mg in producing a complete response (no emesis, no use of rescue medication) during acute (0-24 hours) or delayed (24-120 hours) phases, and similar to intravenous dolasetron 100 mg in acute, but more effective in delayed phase. Palonosetron 0.75 mg was similar to ondansetron (acute and delayed phase) or dolasetron (acute phase), but more effective than dolasetron in delayed phase. In patients receiving highly emetogenic chemotherapy (n = 667), the complete response rates during acute and delayed phases with intravenous palonosetron (0.25 or 0.75 mg) were similar to those seen in intravenous ondansetron 32 mg recipients in a randomised, double-blind trial. Intravenous palonosetron was generally well tolerated in clinical trials, with few adverse events being treatment related. Palonosetron had no significant effect on the corrected QT interval or laboratory parameters.

Pegaptanib, an aptamer, is an antagonist of vascular endothelial growth factor that has shown efficacy in the treatment of patients with exudative age-related macular degeneration (AMD). In two randomised, double-masked trials in patients with exudative AMD (n=1208), the proportion of responders (those losing <15 letters of visual acuity) at 54 weeks was significantly higher in intravitreous pegaptanib 0.3 mg recipients than in those receiving sham injections (70% vs 55%; p<0.001). These trials were conducted concurrently and analysed as a single study; the treatments were given every 6 weeks for 48 weeks. The improvement in visual acuity with pegaptanib was maintained in a 1-year extension of these trials. Similar favourable results with pegaptanib 0.3 mg were seen in terms of the secondary efficacy endpoints (e.g. proportion of patients experiencing severe loss of visual acuity or legal blindness in the study eye). These vision-improving effects of pegaptanib were associated with beneficial angiographic effects. Intravitreous pegaptanib 0.3-3 mg was well tolerated with most ocular adverse events being mild-to-moderate and transient. Serious injection-related adverse events occurred in

Nelfinavir (Viracept) is an orally administered protease inhibitor. In combination with other antiretroviral drugs (usually nucleoside reverse transcriptase inhibitors [NRTIs]), nelfinavir produces substantial and sustained reductions in viral load in patients with HIV infection. Nelfinavir may be used in the treatment of adults, adolescents and children aged >or=2 years with HIV infection. It can also be used in pregnancy. Resistance to nelfinavir may develop, but the most common mutation (D30N, appearing mainly in HIV-1 subtype B) does not confer resistance to other protease inhibitors, thereby conserving these agents for later use. Although less effective than lopinavir/ritonavir, the preferred first-line treatment in US guidelines, nelfinavir is positioned as an alternative agent for the treatment of adults and adolescents with HIV infection and is an option for those unable to tolerate other protease inhibitors. Nelfinavir also has a role in the management of pregnant patients as well as paediatric patients with HIV infection.

Lubiprostone (Amitiza) is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of the gastrointestinal epithelium, resulting in increased fluid secretion. In two pivotal, randomised, double-blind, multicentre phase III studies in patients with chronic idiopathic constipation, the frequency of spontaneous bowel movements (SBMs) was significantly greater in patients receiving lubiprostone 24microg twice daily than in those receiving placebo at each weekly timepoint throughout both 4-week studies (p < 0.05). At week 1 in one pivotal trial, the mean frequency of SBMs in the lubiprostone group was 5.9 per week compared with 4.0 per week in the placebo group (p < 0.0001) [baseline SBMs 1.3 and 1.5 per week]. Significantly greater improvements occurred with lubiprostone than placebo in the degree of straining, stool consistency and constipation severity (where reported) in both pivotal studies (p < 0.05 for all comparisons at all timepoints). Lubiprostone was generally well tolerated in clinical trials with no reports of treatment-related serious adverse events in pivotal trials. Nausea was the most common adverse event, occurring in up to 31% of patients receiving lubiprostone.

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based), rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other fibrin-specific thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.