Intravenous morphine can avoid distressing constipation associated with oral morphine: a retrospective analysis of our experience in 11 patients in the palliative care in-patient unit

Morphine is the preferred strong opioid analgesic. Most of the adverse effects, such as daytime drowsiness, dizziness, mental clouding, and effects on cognitive and psychomotor function or nausea and vomiting, usually resolve with time. The main continuing adverse effect of morphine is constipation, and prophylactic use of laxative is almost always required. We are presenting retrospective data of 11 patients admitted in our palliative care unit over the past 5 months for new (not yet received any opioid analgesic in any form) and severe cancer pain management. It was found that none of the patients was having constipation with intravenous morphine. This finding can be explained on the basis of differences in pharmacologic profiles, in affinity to opioid receptor, and a higher exposure of opioid-binding receptor in the GI tract after oral administration of morphine compared with intravenous morphine. This explanation was further affirmed as constipation and need for laxative was reported by 7 of the 11 patients when they were given the equi-analgesic oral doses of morphine. Thus, the route of administration seems to be responsible for the above finding; hence, further evaluation with prospective observation and data collection is being planned to look for external validity in a larger population catered by our palliative care unit.     

A bioadhesive delivery system as an alternative to infiltration anesthesia

Objective. The aim of this study was to determine the feasibility of a novel saliva-activated bioadhesive drug delivery system of lidocaine hydrochloride as a viable alternative to infiltration anesthesia in dentistry.Study design. The study was carried out in three stages. First, the drug delivery system (DDS) was subjectively evaluated for adherence to the gingival mucosa and peak effect of anesthesia. In the second stage, a comparative subjective and objective evaluation of the DDS with a marketed topical gel preparation was carried out. Finally an open label, nonblinded clinical trial was carried out using the exodontia model. A total of 49 extractions were attempted in 41 patients. The effect of the following variables was investigated in the study: (1) jaw (maxillary and mandibular), (2) overall mobility, (3) position-notation of tooth (1, 2, 3, 4…). The positive extractions were statistically analyzed by the t test comparison of means of two independent variables.Results. Subjective evaluation revealed that the DDS adheres to the gingiva within a minute and produces peak effect in 15 minutes. Comparative study revealed that the DDS produces greater depth of anesthesia than the marketed topical gel. Of 49 extractions attempted with the DDS, 40 were successful, giving an efficacy of 81.63%.Conclusion. The novel saliva-activated bioadhesive drug delivery system of lidocaine hydrochloride exhibits potential as a feasible alternative to infiltration anesthesia in dentistry.     

Influence of serotonin-transporter-linked promoter region polymorphism on platelet activation in geriatric depression.

OBJECTIVE: Depression has been associated with increased platelet activation. Variations in the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism may influence the degree of activation. The authors examined the association among depression, platelet activation, and 5-HTTLPR genotype. METHOD: Elderly subjects with (N=61) and without (N=12) major depression were assessed for cognitive impairment, cardiovascular disease, and two indices of platelet activation. The depressed subjects were genotyped for the 5-HTTLPR polymorphism. RESULTS: The depressed subjects were older, were more cognitively impaired, and had higher platelet factor 4 and beta-thromboglobulin levels; cardiovascular disease was minimal in both groups. In the depressed group, subjects with the 5-HTTLPR l/l genotype had significantly higher platelet factor 4 and beta-thromboglobulin levels. CONCLUSIONS: Platelet activation is increased in elderly depressed patients, especially those with the 5-HTTLPR l/l genotype. This finding suggests how genetic differences may influence cardiovascular mortality in depressed patients with ischemic heart disease.     

Role of postchemotherapy adjunctive surgery in the management of patients with nonseminoma arising from the mediastinum.

PURPOSE: To evaluate the role of postchemotherapy surgery in patients with nonseminomatous germ cell tumors arising from the anterior mediastinum. PATIENTS AND METHODS: Thirty-two patients with nonseminoma arising from a mediastinal primary site were treated on a clinical trial at our center, and they underwent postchemotherapy surgery. The results of postchemotherapy surgical resection, frequency of viable tumor found during postchemotherapy surgery, and prognostic factors for survival were assessed. RESULTS: Complete resection of all gross residual disease was achieved in 27 patients (84%). Histologic analysis of resected residua postchemotherapy revealed viable tumor in 66%, teratoma in 22%, and necrosis in 12% of the specimens. Viable tumor included embryonal carcinoma, choriocarcinoma, yolk sac carcinoma, seminoma, and teratoma with malignant transformation to nongerm cell histology (eg, sarcoma). Clinical characteristics associated with a shorter survival after surgery included the presence of viable tumor in a resected specimen (P =.003) and more than one site resected during surgery (P =.06). There were no statistically significant differences in survival for patients who underwent surgical resection with normal markers compared with patients with elevated serum tumor markers (P =.33). A trend toward shorter survival was found in patients with increasing tumor markers before surgery compared with patients with normal and declining serum tumor markers (P =.09). CONCLUSION: Surgical resection of residual mass after chemotherapy plays an integral role in the management of patients with primary mediastinal nonseminoma. Teratoma and viable tumor were found in the majority of resected residua after chemotherapy. Because patients who undergo conventional salvage chemotherapy programs rarely achieve long-term disease-free status, selected patients with elevated markers after chemotherapy are considered candidates for surgical resection.     

Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers

The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways. Similarly, a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria, endoplasmic reticulum (ER) and Golgi. This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization. Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specific endocytic pathway.KEY WORDS: Amphiphilic, Copolymer, Nanoparticles, Internalization, Intracellular fate     

Analysis of COVID-19-associated rhino-orbital-cerebral mucormycosis patients in a tertiary care center in Northern India

Purpose:An unprecedented surge has been noted in rhino-orbital-Cerebral mucormycosis (ROCM) in times of current COVID-19 pandemic. The present prospective study aims to evaluate clinico-epidemiological profile, risk factors, management, and outcome of the cases of ROCM that presented to our tertiary care center during the study period from April to June 2021.Methods:All patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were staged and were treated with intravenous liposomal amphotericin B (AMB) and sino-nasal debridement of local necrotic tissue. Transcutaneous retrobulbar AMB (TRAMB), orbital decompression, and exenteration were instituted as indicated. All patients were followed up for a minimum of 6 months before arriving at the final outcome. Statistical analysis was performed.Results:A total of 49 patients presented during the study period, with a mean age of 42.2 years. The major risk factors included uncontrolled diabetes (89.8%), COVID-19 positivity (51.02%), and concurrent steroid use (38.77%). The most common presenting symptom was facial pain/swelling (43.65%), while the most common presenting sign was deterioration in vision (75.51%). Intravenous liposomal AMB was given to all patients along with sino-nasal debridement (85.71%), TRAMB (57.14%), orbital decompression (14.28%), and exenteration (12.24%). Overall, mortality at 6 months was 22.45% (11 patients). Age more than 60 years, intracranial extension, and HbA1c of more than 8.0% were observed to be statistically significant indicators of mortality.Conclusion:Early suspicion and timely diagnosis of mucormycosis at rhino-orbital stage is warranted in order to salvage life as well as visual function. TRAMB may prove as potentially favorable treatment modality in cases with limited orbital involvement.