Neuropathic pain is difficult to diagnose and difficult to treat with certainty. So the aim of the study was to evaluate comparative clinical efficacy of pregabaline with amitriptyline and gabapentin in neuropathic cancer pain. A total of 120 patients with cancer having severe neuropathic cancer pain were enrolled in the study after taking approval from Institutional Ethics Committee and divided in to 4 groups: group AT-amitriptyline, group GB-gabapentin, group PG-pregabalin, and group PL-placebo. Oral morphine was used for rescue analgesic for continued pain. Pain score (Visual Analogue scale) and secondary outcome measures such as intensity of lancinating, dysesthesia, and burning on numerical rating scale, Global satisfaction score (GSS), Eastern Co-operative Oncology Group scoring (ECOG), and adverse effects were assessed. At the end of study there was significant decrease in pain score in group PG as compared to the other groups; group AT (P = .003), group GB (P = .042), and group PL (P = .024). Percentage of patients with lancinating pain and dysesthesia were significantly less in group PG as compared to groups GB and PL. All the patients in group PL needed rescue morphine. After 4 visits, maximum improvement in ECOG scoring and GSS scoring was observed in group PG patients. Our results suggested that all antineuropathic drugs are effective in relieving cancer-related neuropathic pain. There was statistically and clinically significant morphine sparing effect of pregabaline in relieving neuropathic cancer pain and neuropathic symptoms as compared to other antineuropathic drugs.
Hypoxia is a hallmark of solid tumors including glioblastoma (GBM). Its synergism with Notch signaling promotes progression in different cancers. However, Notch signaling exhibits pleiotropic roles and the existing literature lacks a comprehensive understanding of its perturbations under hypoxia in GBM with respect to all components of the pathway. We identified the key molecular cluster(s) characteristic of the Notch pathway response in hypoxic GBM tumors and gliomaspheres. Expression of Notch and hypoxia genes was evaluated in primary human GBM tissues by q-PCR. Clustering and statistical analyses were applied to identify the combination of hypoxia markers correlated with upregulated Notch pathway components. We found well-segregated tumor—clusters representing high and low HIF-1α/PGK1-expressors which accounted for differential expression of Notch signaling genes. In combination, a five-hypoxia marker set (HIF-1α/PGK1/VEGF/CA9/OPN) was determined as the best predictor for induction of Notch1/Dll1/Hes1/Hes6/Hey1/Hey2. Similar Notch-axis genes were activated in gliomaspheres, but not monolayer cultures, under moderate/severe hypoxia (2%/0.2% O2). Preliminary evidence suggested inverse correlation between patient survival and increased expression of constituents of the hypoxia-Notch gene signature. Together, our findings delineated the Notch-axis maximally associated with hypoxia in resected GBM, which might be prognostically relevant. Its upregulation in hypoxia-exposed gliomaspheres signify them as a better in-vitro model for studying hypoxia-Notch interactions than monolayer cultures.
Introduction:The phantom limb pain (PLP) and phantom limb sensation (PLS) are very common among amputated cancer patients, and they lead to considerable morbidity. In spite of this, there is a lack of epidemiological data of this phenomenon among the Asian population. This study was done to provide the data from Indian population.Methods:The prevalence of PLP, stump pain (SP), and PLS was prospectively analyzed from the amputated cancer patients over a period of 2 years in Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi. The risk factors and the impact of phantom phenomenon on patients were also noted.Results:The prevalence of PLP was 41% at 3 and 12 months and 45.3% at 6 months, whereas that of SP and PLS was 14.4% and 71.2% at 3 months, 18.75% and 37.1% at 6 months, 15.8% and 32.4% at 12 months, respectively. There was higher prevalence of PLP and PLS among the patients with history of preamputation pain, smoking with proximal level of amputation, receiving general anesthesia, receiving intravenous (IV) opioid postoperative analgesia, and developing neuroma or infection.Conclusion:The prevalence of PLP and PLS was higher among the cancer amputees as compared to SP, and a few risk factors responsible for their higher prevalence were found in our study. The PLP and PLS lead to considerable morbidity in terms of sleep disturbance and depression.
The anterior USG-guided superior hypogastric plexus neurolysis is a useful technique in relieving pelvic pain in gynecological malignancies. However, it requires expertise to perform the block. It also avoids the radiation exposure involved with computed tomography-guided and fluoroscopy-guided superior hypogastric block.
bRadicicol, an antifungal antibiotic, was previously identified as a compound having antimalarial activity. However, its mechanism of action in Plasmodium falciparum was not elucidated. While characterizing its antimalarial function, we observed that radicicol manifested two distinct developmental defects in cultured P. falciparum in a concentration-dependent manner. At a low concentration of radicicol, a significant percentage of drug-treated parasites were arrested at the schizont stage, while at a higher concentration, the parasites were unable to multiply from schizont to ring. Also, the newly formed rings and trophozoites were extremely delayed in development, eventually leading to cell death. We intended to characterize the potential molecular target of radicicol at its sublethal doses. Our results demonstrated that radicicol specifically impaired mitochondrial replication. This decrement was associated with a severalfold increment of the topoisomerase VIB transcript as well as protein in treated cells over that of untreated parasites. Topoisomerase VIB was found to be localized in the organelle fraction. Our docking study revealed that radicicol fits into the Bergerat fold of Pf topoisomerase VIB present in its ATPase domain. Altogether, these data allow us to conclude that P. falciparum topoisomerase VIB might be one of the targets of radicicol causing inhibition of mitochondrial replication. Hence, radicicol can be suitably employed to explore the mitochondrial physiology of malaria parasites.
In most operating and recovery rooms, shivering is controlled by the use of humidifiers, warming blankets, and inhalation of humidified heated oxygen. However, pharmacological control is an effective alternate treatment modality. This randomized, double-blind trial, conducted in 30 ASA Grade I or 2 patients, was designed to explore the efficacy of tramadol and pethidine in the treatment of post-anaesthetic shivering.Tramadol is an inhibitor of the re-uptake of serotonin (5-hydroxytryptamine) and norepinephrine in the spinal cord. This facilitates 5-hydroxytryptamine release, which influences thermoregulatory control. We compared the efficacy of tramadol with that of pethidine, presently a widely used drug for the control of shivering. Patients received either tramadol 1mg/kg or pethidine 0.5 mg/kg intravenously and the grade of shivering, pulse rate, blood pressure and respiratory rate were observed every 10 minutes after injection for one hour. Shivering was significantly more likely to have ceased in the tramadol group (12 of 15 versus 4 of 15 cases, P<0.05) at 10 minutes after drug administration and this control was better sustained. No patients receiving tramadol had a recurrence of shivering. It is concluded that intravenous tramadol 1 mg/kg is more effective for the treatment of postoperative shivering than pethidine 0.5 mg/kg.
While deciding about the ethical issues, the physicians and nurses do not restrict their considerations to the physical aspects of the disease, but also reflect upon the complex wider consequences of the treatment decisions.
Attention to psychosocial and spiritual health needs of patients with cancer is an integral part of an effective palliation, though they are less commonly expressed but are strongly felt by patients with cancer. It is therefore recommended that all clinicians and health care providers should address psychosocial health needs as a part of their routine practice.
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