Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients

Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 10⁹ platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6–13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan–Meier curve). Predictive factors (univariate analysis) of an initial and long‐term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost.     

Comparison of Observational and Controlled Clinical Trials of Diltiazem in the Treatment of Chronic Anal Fissure

Diltiazem has been extensively studied in the treatment of chronic anal fissures, but efficacy in clinical practice is not fully established. The aim of the present study was to evaluate the safety and efficacy of topical application diltiazem in observational studies as well as in controlled clinical trials in the treatment of chronic anal fissures. A systematic literature search was carried out from 1966 to 31 December, 2007 on PubMed, Medline, Embase and Cochrane database, using the appropriate search words. We found six observational studies with 392 patients and five controlled clinical trials with 289 patients in which topical diltiazem treatment was given. Efficacy was found to be very high in observational studies (56.88%), whereas it was found to be modest in controlled clinical trials (29.41%). In observational studies, most of the patients reported complete healing of fissures within 6–12 weeks, whereas in controlled trials healing was reported within 8 weeks, with tolerable adverse effects of diltiazem. On the basis of the above studies, it can be concluded that topical application of diltiazem is useful in the treatment of chronic anal fissure, but to fully establish its efficacy, larger prospective double-blind study is required in the near future.     

Cure and reinfection patterns of geohelminthic infections after treatment in communities inhabiting the tropical rainforest of Assam, India

Mass de-worming targeted at socio-economically poor communities can be considered as an option for communities living in the tropical forests of Assam who do not have access to safe drinking water and proper sanitation, and consequently have a higher risk of suffering from geohelminthic infection and associated morbidity. A random sample of 265 subjects was included in this study (134 males and 131 females). The chemotherapeutic regimen followed was a single dose of albendazole 400 mg. Stools samples were collected in 10% formol-saline for detection of infection before treatment. Post-treatment stool samples were collected 10 to 14 days after treatment to determine the cure rate. Stool samples were again collected 3 to 6 months post-treatment to study the rate of reinfection. Multiple logistic regression was used to find possible associations between age, sex and treatment failure. The chi-square test was used wherever appropriate. The cure rates for Ascaris lumbricoides, Trichuris trichiura and hookworms were 70.8%, 68.7% and 93.0%, respectively. Logistic regression revealed that age was associated with treatment failure in A. lumbricoides infection. Re-infection rates after 3 months of successful treatment were 19.6% for A. lumbricoides, 30.9% for T. trichiura and 11.3% for hookworms. Six months post-treatment, the prevalence of re-infection was highest with T. trichiura (43.6%); followed by A. lumbricoides (35.3%). The rate of reinfection with hookworms was lower (11.3%) six months post-treatment. The rates of re-infection with A. lumbricoides and T. trichiura was higher in children below 15 years of age, compared with adults. Hookworm reinfection was higher in the adult age group (15 to 39 years). The rates of new infection in previously uninfected subjects were lower compared with the rates for re-infection.     

Emerging role of uterine natural killer cells in establishing pregnancy

Normal pregnancy has been considered as a controlled state of inflammation at an early stage of blastocyst implantation that subsequently develops systemically. Till recent past most popular hypotheses regarding status of immune system in pregnancy were dominated by the Th1 and Th2 hypothesis, in which the fetus avoids maternal rejection through a bias towards T-helper (Th2) cytokine production. Recent findings have shown that predominant immune interactions in the human deciduas are between the placental trophoblast and maternal uterine natural killer (uNK) cells rather than the T cells. Thus NK cells are emerging as important players in the uterine immune response to invasive forms of placenta, as in cases of hemochorial placenta. In humans there is a lack of evidence for T-cell responses to trophoblast cells; therefore it was thought that uterine NK cells are the key factors by which the maternal immune system recognizes trophoblast cells. In this review we are trying to summarize the role of uNK cells in the maintenance of normal pregnancy in humans.     

Long-term sequelae of herpes simplex virus encephalitis–related white matter injury: correlation of neuropsychological outcome and diffusion tensor imaging

Journal of NeuroVirology - The pathophysiology of the memory impairment following Herpes Simplex virus encephalitis is not yet established and understood. This study attempts to elucidate the role...     

Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy

Objective:

The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers.

Methods:

All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers.

Results:

A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom''s/van Herk''s formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions.

Conclusion:

Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers.

Advances in knowledge:

Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.     

Drug development status for Alzheimer’s disease: present scenario

Recent advances in the understanding of Alzheimer’s disease pathogenesis have led to the development of numerous compounds that might ameliorate the disease process. Research in the field of Alzheimer’s disease therapy has been partly successful in terms of developing symptomatic treatments, but also had several failures in terms of developing disease-modifying therapies. These successes and failures have led to a debate about the potential deficiencies in our understanding of the pathogenesis of Alzheimer’s disease and potential pitfalls in diagnosis, choice of therapeutic targets, development of drug candidates, and design of clinical trials. Many clinical and experimental studies are ongoing, but we need to acknowledge that a single cure for Alzheimer’s disease is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered. Preclinical research is constantly providing us with new information on pieces of the complex Alzheimer’s disease puzzle, and an analysis of this information might reveal patterns of pharmacological interactions instead of single potential drug targets. Several promising randomized controlled trials are ongoing, and the increased collaboration between pharmaceutical companies, basic researchers, and clinical researchers has the potential to bring us closer to developing an optimum pharmaceutical approach for the treatment of Alzheimer’s disease.     

Factors associated with HIV among female sex workers in a high HIV prevalent state of India

The study was carried out to assess the factors associated with HIV seropositivity among female sex workers (FSWs) in Dimapur, Nagaland, a high HIV prevalence state of India. A total of 426 FSWs were recruited into the study using respondent driven sampling (RDS). Data on demographic characteristics, sexual and injecting risk behaviours were collected from them and were tested for HIV, Syphilis, Neisseria gonorrhoeae and Chlamydia trachomatis. RDS-weighted univariate and multivariate logistic regression analysis was performed to assess the factors associated with HIV seropositivity. Consistent condom use with regular and occasional sexual clients was 9% and 16.4%, respectively. About 25% of the participants ever used and 5.7% ever injected illicit drugs. RDS adjusted HIV prevalence was 11.6%. In the univariate analysis, factors associated with HIV were initiating sexual intercourse before the age of 15 years, ≥2 years duration of sex work, serving clients at lodge/hotel, positive test result for one or more sexually transmitted infections (STIs), lifetime history of injecting drug use, lifetime history of consuming illicit drugs, ever having exchanged sex for drugs, having sexual partners who engaged in risky injecting practices and having been widowed or divorced. In multivariate analysis, factors found to be independently associated with HIV included lifetime injecting drug use, initiating sexual intercourse before the age of 15 years, positive test result for one or more STIs and having been widowed. Injecting drug use was found to be most potent independent risk factor for HIV (OR: 3.17, CI: 1.02-9.89). Because of lower consistent condom use among them, FSWs may act as bridge for HIV transmission to general population from injecting drug users (IDU) through their sexual clients. The informations from this study may be useful for enriching the HIV preventions effort for FSWs in this region.